VOL. 38, NO.

2 º 2005
HONORINC 1HL LIFL AND CON1RI8U1IONS OF H. C. 8ROWN
Herbert C. ßrovn and AIdrich.
Advancing ßorane Chemistry !or 32 Years
Organotriñuoroborates.
Expanding Organoboron Chemistry
Recent Advances in the Chemistry
o! Lithium Aminoborohydrides
R£AG£NTS IOR AS¥MM£TRlC S¥NTH£SlS
(R)-(+)-o-ToIyI-Cß5-oxazaboroIidine soIution, 0.5 M in toIuene
65,429-9 5 mL S3!.50
25 mL !09.00
(S)-(-)-o-ToIyI-Cß5-oxazaboroIidine soIution, 0.5 M in toIuene
65,430-2 5 mL S3!.50
25 mL !09.00
New Products from Aldr¡ch R&D
Please see pages 56, 58, and 59 for additional new products.
For compeIiIive quoIes oh larger quahIiIies, cohIacI safcglobal.com.
The SAlC logo, lnspiring Science, and Sure/Seal are lrademarks ol Sigma-Aldrich 8iolechnology, L.P.
R£AG£NT IOR C-X 8OND IORMATlON
DimethyI thiophosphonate, 97%
65,531-7 ! g S62.00
5 g 2!6.00
Peacls wilh imines under mild condilions and wilhoul demelhylalion lo
lorm A-aminophosphonolhionales.
Tongcharoensirikul, P. el al. I. Orq. Chem. 2004, 69, 2322.
8UlLDlNG 8LOCK
3-ChIoro-4-methoxyphenethyIamine hydrochIoride
65,632-1 5 g S80.00
A uselul slarling malerial lor lhe synlhesis ol many nalural producls, such as
!,2,3,4-lelrahydroisoquinolines
!
and 2,3,4,5-lelrahydro-!|-3-benzazepines.
2
(!) Charilson, P. S. el al. I. |ed. Chem. 1988, J1, !94!. (2) Chumpradil, S.
el al. I. |ed. Chem. 1991, J4, 877.
LlGANDS IOR CATAL¥SlS
Tri-tert-butyIphosphine soIution, 1 M in toIuene
65,532-5 !0 mL S66.00
50 mL 230.00
This low-melling, air-sensilive, and pyrophoric solid is now available as an
easier-lo-use loluene solulion in a Sure/Seal
¹
bollle.
tert-ßutyIdicycIohexyIphosphine, 97%
65,160-5 ! g S49.00
5 g !72.00
This novel phosphine was used lo prepare calalysls lor lhe ring-opening
melalhesis polymerizalion ol cyclooclene.
Jan, D. el al. I. Orqanome|. Chem. 2000, 606, 55.
R£AG£NTS IOR CROSS-COUPLlNG R£ACTlONS
2-MethyIpyridin-5-yI tri!IuoromethanesuI!onate, 97%
64,848-5 ! g S25.00
5 g 78.00
Aclivaled lrillales ol lhis lype have served as allernalives lo aryl halides in
a variely ol palladium-calalyzed coupling reaclions.
!3
5-ChIoroquinoIin-8-yI tri!IuoromethanesuI!onate, 97%
64,850-7 ! g S42.00
5 g !24.00
(!) Mallhews, D. P. el al. 1e|rahedron |e||. 1994, J¯, 5!77. (2) Tilley, J. W.,
Zawoiski, S. I. Orq. Chem. 1988, ¯J, 386. (3) Lllingboe, J. W. el al. I. |ed.
Chem. 1994, J7, 542.
Lxcellenl reagenls lor calalylic asymmelric lranslormalions such as lhe
DielsAlder reaclion
!
and lhe cyanosilylalion ol aldehydes.
!,2
Chiral calionic
oxazaborolidines, prepared lrom o-lolyloxazaborolidine and lrillic acid,
calalyze DielsAlder reaclions lo provide high ee's.
3
Pecenlly, Corey and co-
workers used lhese calalysls lo synlhesize several chiral nalural producls,
olherwise synlhesized in racemic lorm.
4
(!) Corey, L. J. el al. I. Am. Chem. 5oc. 2002, 124, 3808. (2) Pyu, D. H.,
Corey, L. J. I. Am. Chem. 5oc. 2004, 126, 8!06. (3) Pyu, D. H. el al. I. Am.
Chem. 5oc. 2002, 124, 9992. (4) Hu, O.-Y. el al. I. Am. Chem. 5oc. 2004,
126, !3708.
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AIdrich ChemicaI Co., Inc.
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VOL. 38, NO. 2 º 2005
"PLEA5E BOIHER U5."
Dr. lan J. S. lairlamb ol lhe Universily ol York, U.K., kindly suggesled lhal we oller lhis Suzuki
Miyaura cross-coupling palladium calalysl in our calalog. Palladium-calalyzed cross-coupling
reaclions conslilule some ol lhe mosl imporlanl and applied lranslormalions lor lhe synlhesis
ol nalural producls, pharmaceulical largels, and conjugaled malerials.
!
This palladium calalysl
has shown a higher aclivily over Pd
2
(dba)
3
in lhe SuzukiMiyaura cross-coupling ol organic
halides wilh arylboronic acids.
2

(!) |andboo| o| Orqanooa||ad|um Chem|:|rv |or Orqan|c 5vn|he:|:, Negishi, L., Ld., Wiley. Hoboken, NJ, 2002.
(2) lairlamb, l. J. S., Kapdi, A. P., Lee, A. l. Orq. |e||. 2004, 6, 4435.
65,693-3 ßis(3,5,3',5'-dimethoxydibenzyIideneacetone)- ! g S!9.65
paIIadium(0) |Pd(dm-dba)
2
¦ 5 g 65.50
Nalurally, we made lhis uselul calalysl. ll was no bolher al all, jusl a pleasure lo be able
lo help.
|o vou have a comoound |ha| vou w|:h A|dr|ch cou|d ||:|. and |ha| wou|d he|o vou |n vour
re:earch bv :av|nq vou ||me and monev? || :o. o|ea:e :end u: vour :uqqe:||on. we w||| be
de||qh|ed |o q|ve || care|u| con:|dera||on. You can con|ac| u: |n anv one o| |he wav: :hown on
|h|: oaqe and on |he |n:|de bac| cover.
IABLE OF CONIENI5
Herbert C. ßrovn and AIdrich. Advancing ßorane Chemistry !or 32 Years . . . . . . . . . . . . . . . . . . . . 43
C||n|on |. |ane. Norlhern Arizona Universily
Organotriñuoroborates. Expanding Organoboron Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Carv A. |o|ander¯ and |u|h ||queroa. Universily ol Pennsylvania
Recent Advances in the Chemistry o! Lithium Aminoborohydrides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
|ubov |a:uman:|v and ba||han 5|nqaram.¯ Universily ol Calilornia, Sanla Cruz,
and Chr|:||an 1. Cora|:||. CTC Consulling
ABOUI OUR COVER
1he |amoar|: a| A|que:-|or|e: (oil on
canvas, 60 × !00 cm) was painled and
signed by lhe arlisl lrederic 8azille in
!867. Probably lew lourisls who visil lhe
lamous classical ruins al Nimes and Arles in
soulhern lrance are aware lhal nearby is lhe
besl-preserved medieval lorlress in Lurope,
lhe subjecl ol lhis painling. ln !246, King
Louis lX began lhe lower seen jusl lo lhe
lell ol lhe cenler ol lhis piclure and had a
lve-mile channel dug lhrough lhe esluary
ol lhe Phone river lo lhe Medilerranean lor
ships embarking on lhe Sevenlh and Lighlh
Crusades. His son, Philippe lll, slarled lhe enormous adjoining balllemenls in !272, bul, wilhin
less lhan a cenlury, silling closed lhe passage lo lhe sea and lhe slruclure was abandoned.
8azille was born nol lar away al Monlpellier lo a well-lo-do lamily and was expecled lo
become a doclor. While slill in medical school, however, he convinced his lalher lo subsidize his
arlislic educalion in Paris. He soon became lasl lriends wilh Allred Sisley, Augusle Penoir, and
Claude Monel, who suggesled lo 8azille and lhe olhers lhal lhey painl oul-ol-doors direclly in
lronl ol lheir subjecls, lhus inilialing lhe essenlial aspecl ol impressionisl painling. When in lhe
spring ol !867 8azille wenl lo painl 1he |amoar|: a| A|que:-|or|e:, he wrole lo his molher
lhal he inlended lo painl "a very simple painling" ol "lhe walls ol lhe cily relecled in a pond
al sunsel". The composilion ol lhe piclure is indeed very simple, delned by lhe diagonal ol lhe
sandbar in lhe loreground and lhe almosl equal areas ol waler and sky on eilher side ol lhe
long horizonlal ol lhe ramparls. The view is lo lhe easl, wilh lhe lale allernoon sun slriking lhe
walls ol lhe lorlress. A lower near lhe righl edge ol lhe painling is relecled in lhe waler, and
lhe pink linge ol lhe clouds suggesls lhe coming sunsel.
This painting is a part o! the CoIIection o! Mr. and Mrs. PauI MeIIon at the NationaI
GaIIery o! Art, Washington, DC.
1oe Porwoll, PresidehI
Pholograph © 8oard ol Truslees, Nalional Callery ol Arl, Washinglon.
The 5eIectride
®
famiIy
The Seleclride
®
lamily ol boranes is a group ol powerlul reagenls
lor lhe asymmelric reduclion ol kelones on complex scallolds. These
reagenls have been used in lhe synlhesis ol many nalural producls,
7

in lhe slereoseleclive reduclion ol hemiacelals in various nucleoside
synlheses,
8
and are capable ol ellecling reduclive cyclizalion
9
and
rearrangemenl reaclions.
!0
(7) Some recenl examples. (a) 8ahia, P. S., Snailh, J. S. I. Orq. Chem. 2004, 69, 3226. (b)
Thede, K. el al. Orq. |e||. 2004, 6, 4595. (c) 8anwell, M. C. el al. Orq. |e||. 2004, 6,
2737. (d) Lichlenlhaler, l. W. el al. 1e|rahedron. A:vmme|rv 2003, 14, 727. (e) Nelson,
T. D. el al. 1e|rahedron |e||. 2004, 4¯, 89!7.
(8) (a) Hanessian, S., Machaalani, P. 1e|rahedron |e||. 2003, 44, 832!. (b) Navarre, J.-M. el
al. 1e|rahedron |e||. 2003, 44, 2!99.
(9) Nagaoka, Y. el al. 1e|rahedron |e||. 2002, 4J, 4355.
(!0) (a) Chen, W. el al. I. Orq. Chem. 2003, 63, !929. (b) Appendino, C. el al. |ur. I. Orq.
Chem. 2003, 4422.
for competitive quotes on Iarger quantities o! aII
o! these organoboranes, pIease contact us at
800-244-1173 (U5A) or at safcglobal.com.
Organoboranes for Asymmetr¡c Synthes¡s
From 5igma-Aldrich
L E A D E R 5 H l P l N L l F E 5 C l E N C E , H l G H I E C H N O L O G Y A N D 5 E R V l C E
ALDRICH º 8OX 355 º MILWAUKLL º WISCONSIN º USA
DIP-ChIoride
¹
and DIP-ßromide
¹
Since ils inlroduclion 20 years ago, DlP-Chloride
¹
(b-chlorodiisopino-
campheylborane, lpc
2
8Cl, DlP-Cl) has become one ol lhe mosl elleclive
reagenls lor lhe asymmelric reduclion ol prochiral kelones, especially
aralkyl and :-hindered kelones.
!
The reagenl has lound popular
use in lhe asymmelric synlhesis ol ligands,
2
;-amino alcohols,
3
and
alkaloids,
4
and is also capable ol ellecling asymmelric aldol reaclions.
5

lurlhermore, asymmelric allylalions can be achieved when DlP-Cl is
reacled wilh allylmagnesium bromide, allowing lor lurlher elaboralion
ol lhe reduced producl. We are now ollering lhis valuable reagenl also
as an easier-lo-handle solulion in lhree dillerenl solvenls. heplane,
hexane, and D-pinene.
DlP-8romide
¹
has been used lor lhe asymmelric reduclion ol kelones,
in enolboralion reaclions, and lor lhe ring opening ol meso epoxides.
6

Sigma-Aldrich is pleased lo oller lhese excellenl reagenls lor asymmelric
synlhesis lo our cuslomers.
(!) (a) Chandrasekharan, J. el al. I. Orq. Chem. 1985, ¯0, 5446. (b) Srebnik, M.,
Pamachandran, P. V. A|dr|ch|m|ca Ac|a 1987, 20, 9.
(2) Drury, W. J., lll el al. Anqew. Chem.. |n|. |d. 2004, 4J, 70.
(3) 8eardsley, D. A. el al. 1e|rahedron |e||. 1994, J¯, !5!!.
(4) lelpin, l.-X., Lebrelon, J. I. Orq. Chem. 2002, 67, 9!92.
(5) Slocker, 8. L. el al. |ur. I. Orq. Chem. 2004, 330.
(6) Dhar, P. K. A|dr|ch|m|ca Ac|a 1994, 27, 43.
DlP-Chloride and DlP-8romide are lrademarks and Seleclride a regislered lrademark ol Sigma-Aldrich 8iolechnology, L.P.
(+)-DIP-ChIoride
¹
31,701-2 5 g S33.50
25 g !08.00
!00 g 300.50
! kg 2!45.00
(-)-DIP-ChIoride
¹
31,702-0 5 g S35.00
25 g !06.00
!00 g 289.50
(-)-DIP-ChIoride
¹
soIution, 65-75 vt. % in :-pinene
65,529-5 25 mL S90.00
!00 mL 225.00
(-)-DIP-ChIoride
¹
soIution, 50-65 vt. % in heptane
64,841-8 25 mL S90.00
!00 mL 225.00
(-)-DIP-ChIoride
¹
soIution, 50-65 vt. % in hexanes
64,842-6 25 mL S90.00
!00 mL 225.00
(+)-DIP-ßromide
¹
, 95%
41,427-1 5 g S74.!0
25 g 270.00
(-)-DIP-ßromide
¹
, 95%
41,099-3 5 g S!77.00
25 g 590.00
L-5eIectride
®
soIution, 1.0 M in tetrahydro!uran
17,849-7 !00 mL S37.40
800 mL 277.00
8 L 93!.00
!8 L !865.00
L5-5eIectride
®
soIution, 1.0 M in tetrahydro!uran
22,592-4 !00 mL S!05.50


K-5eIectride
®
soIution, 1.0 M in tetrahydro!uran
22,076-0 !00 mL S83.30
800 mL 562.00
K5-5eIectride
®
soIution, 1.0 M in tetrahydro!uran
22,077-9 !00 mL S77.40
N-5eIectride
®
soIution, 1.0 M in tetrahydro!uran
21,340-3 !00 mL S48.00
800 mL 257.50
43
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OutIine
1. Introduction
2. BeIore 1972
3. Aldrich-Boranes, Inc.
4. Early Borane Reagents
5. Boranes on a Large Scale
6. Latest Borane Reagents
7. Philanthropy
8. Conclusions
9. ReIerences and Notes
1. Introduction
Nobel Laureate Herbert C. Brown (HCB), the R. B. Wetherill
Research ProIessor Emeritus oI Chemistry at Purdue University,
died on December 19, 2004, at age 92. He will long be
remembered at Aldrich and by the scientiIic community Ior his
extensive contributions to borane chemistry. Brown and Aldrich
maintained a close working relationship that started in 1972
and continued until his death. Interested readers are directed
to his published obituary
1
and to the HCB pages on the Purdue
University Department oI Chemistry Web site.
2
A number oI
essays and notes have also appeared in this magazine, which
provide biographical inIormation and additional details about
HCB and his 32-year relationship with Aldrich.
3

This account will give a personal perspective oI a career-long
relationship with HCB as a thesis adviser and mentor and then
as a consultant and Iriend, and oI how he and I were able to help
Aldrich advance borane chemistry.
2. ße!ore 1972
The late 1960s were exciting times in HCB`s research group at
Purdue. We were actively investigating hydroboration and the
reactions oI organoboranes. The work was being quickly published
as a series oI communications in various iournals.
4
However,
Brown knew his developments would not be widely used until
his new borane reagents were made available commercially.
The SchlesingerBrown process Ior preparing metal
borohydrides was developed on a laboratory scale at the
University oI Chicago in the early 1940s.
5a
In the 1950s, Brown
worked closely with Metal Hydrides (a start-up company in
Massachusetts) on the scale-up oI the process he, Schlesinger,
and Finholt had discovered to produce NaBH
4
.
5b
As expected,
this valuable reagent was widely used by scientists only aIter it
had become commercially available.
Encouraged by the success oI NaBH
4
in research and commerce,
Brown contacted a number oI companies about licensing and
developing his organoborane technology. Between 1969 and
1971, he successively approached the Iollowing companies:
Ventron Corporation (the successor to Metal Hydrides), Ethyl
Corporation, Eastman Kodak, Arapahoe Chemicals, and G. D.
Searle and Company. In each case, the R&D scientists and the
technical management groups at these companies were very
interested and could see the potential Ior his new technology.
However, once the proposals went higher in the organization,
the business development staII would carry out market research
only to Iind a complete absence oI any sales numbers Ior the
products. This was hardly surprising, since the products were not
yet commercially available.
ProIessor Brown never shared the details oI his aIorementioned
contacts with me when I was one oI his Ph.D. students. However,
he did ask me many times iI I would be interested in working in
industry to Iurther the development oI his borane technology. I
always expressed an interest, but I could not wait Ior HCB to Iind
an industrial partner. I leIt Purdue University in the Iall oI 1971,
with my Ph.D. degree still pending, and ioined ProIessor William
T. Miller`s research group at Cornell University as a postdoctoral
research assistant to work on the chemistry oI organoIluorine
compounds.
Herbert C. Brown and Aldrich:
Advancing Borane Chemistry
for 32 Years
Clinton F. Lane
Department of Chemistrv ana Biochemistrv
Northern Arizona Universitv
P.O. Box 5698
Flagstaff. AZ 86011-5698. USA
Email. clint.lane(nau.eau
The author presenting ProIessor Brown with the Iirst ACS H. C. Brown Awara for
Creative Research in Svnthetic Methoas (1998).
44
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3. AIdrich-ßoranes, Inc.
Early in 1972, HCB approached AlIred Bader, the coIounder
and then president oI Aldrich Chemical Co., and suggested
that Aldrich consider oIIering a number oI Brown`s boron-
containing reagents. Dr. Bader (Harvard Ph.D. with Louis Fieser)
recognized the potential Ior Brown`s technology, and oIIered to
establish a subsidiary, Aldrich-Boranes, Inc., to commercialize
all oI Brown`s discoveries. In the summer oI 1972, Brown and
Bader recruited me to become the Iirst outside employee oI this
new company. I started my career with Aldrich in September oI
1972, and Iirst worked Ior Harvey Hopps, an existing Aldrich
employee who had been appointed manager oI Aldrich-Boranes.
HCB became a director oI Aldrich and a consultant to Aldrich-
Boranes, Inc. His existing patents and all Iuture ones covering
all oI his discoveries in boron-based chemistry were assigned to
Aldrich-Boranes.
4. EarIy ßorane Reagents
Aldrich-Boranes occupied Iirst one, then two, and Iinally three
laboratories in Aldrich`s 940 West Saint Paul Avenue Building
in Milwaukee, Wisconsin. During the period Irom 1972 to 1977,
HCB called at least once or twice a week to discuss our progress.
He oIten Iollowed up the phone conversations with long and
detailed letters. As usual, he was always very positive and
optimistic about the chemistry, and would never accept a poor
result Ior any scale-up oI his chemistry. He contributed greatly
to our success and remained interested and available. He visited
us in Milwaukee at least two or three times a year, and I visited
him at Purdue many times each year.
Within a year, ALHB (internal vendor code Ior Aldrich-
Boranes) was successIul in scaling up and developing many
organoborane-based products Ior listing in the Aldrich catalog.
However, we lost money. The Iollowing year (1973), we broke
even. By the end oI the third year, we made enough money to
oIIset all previous losses, and the operations have been proIitable
ever since. The borane reagents developed during this period
(Figure 1) now account Ior many millions oI dollars in annual
sales, with a Iew being among Aldrich`s best-selling products.
HCB was not only a great scientist, but also a good businessman.
He took an interest in all aspects oI our business, especially the
advertising and promotion oI our products. He encouraged me to
expand some oI our advertisements into detailed reviews suitable Ior
publications. These were published in various reIereed iournals and
then condensed into shorter reviews Ior this magazine.
6
In addition,
HCB contributed a review on the subiect and encouraged one oI his
postdoctoral assistants to submit another.
7
These helped promote our
borane products and contributed greatly to our early success.
5. ßoranes on a Large 5caIe
By our Iourth year (1976), ALHB was starting to outgrow
the space it occupied in Milwaukee, and desperately needed
additional space to meet the market demand Ior borane reagents.
Fortunately, we were able to purchase a small chemical plant
in rural Sheboygan County about 50 miles north oI downtown
Milwaukee. ALHB moved to this new site in early 1978, and has
continued to show strong growth to this day. My three chemist
associates Irom Milwaukee (John Daniels, Wayne Adler, and Jim
SaraIin) ioined me in our move to the Sheboygan site. The three
are currently part oI the management team at the Sheboygan site
oI Sigma-Aldrich, Aldrich`s successor company. HCB`s long-
term relationship with Aldrich is thus reIlected in the long-term
careers oI many oI Aldrich`s chemists.
Today, Sigma-Aldrich operates Iive maior plants on the 513-
acre Sheboygan site. The production, packaging, and utilization
oI air-sensitive reagents remain an important part oI operations
at the site (Figure 2). Various borane reagents remain key
compounds in production there, and new borane reagents
continue to be developed at the site.
6. Latest ßorane Reagents
Hundreds oI additional and useIul boron-based reagents were
discovered in Brown`s laboratories at Purdue in the 20¹ years
Iollowing his winning oI the Nobel Prize in 1979. Sigma-Aldrich`s
R&D scientists worked very hard, with steady encouragement
Irom HCB, to scale up and oIIer as many oI his new borane
reagents as possible. It is impossible to list all oI these newer
reagents in this short account, but Figure 3 gives a representative
sample. Brown continued to write and encourage his co-workers
to write reviews Ior this magazine to promote his latest borane
discoveries.
8
It is interesting to note that the maiority oI HCB`s
work on reagents Ior asymmetric synthesis occurred aIter he
received the Nobel Prize. The :-pinene-derived reagents could
prove to be the most useIul yet (Figure 4).
8e
7. PhiIanthropy
In 1960, Brown was promoted to R. B. Wetherill Research
ProIessor. A signiIicant part oI the promotion package stipulated
that HCB would be given personal ownership oI all his existing
and Iuture patents. This was quite an unusual arrangement,
but it enabled Brown to easily work with AlIred Bader on the
Figure 2. HerberI ahd Sarah 8rowh ih 1999 hear PRO I,
Ihe 8uildihg DedicaIed Io Ihe ProducIioh o! Air-SehsiIive
Compouhds aI Ihe Sigma-Aldrich SiIe hear Sheboygah, WI.
Figure 1. Larly 8orahe ReagehIs
Developed ahd O!!ered by Aldrich.
45
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5
establishment oI Aldrich-Boranes, Inc. Brown personally
received royalty payments on the sales oI all borane reagents
sold by Aldrich. It might appear that Purdue gave up signiIicant
Iinancial gains to keep a rising star. However, rewards come to
those who wait.
In 1983, Herb and Sarah Brown endowed a special Iund to
establish and Iinance the Herbert C. Brown Lectures at Purdue.
Every year since 1984, 35 world-class chemists are invited to
Purdue to present a lecture on a Saturday in April. Interestingly,
when the Department oI Chemistry at Purdue Iirst proposed
these lectures, the plan was to seek Iinancial contributions Irom
HCB`s Iormer students and Iriends. Sarah reiected this idea and
proposed that she and Herb provide all the necessary Iunds.
HCB was the Iirst winner oI the American Chemical Society
Herbert C. Brown Award Ior Creative Research in Synthetic
Methods (1998). Aldrich proposed this award to the ACS, and
the endowment Iunds came Irom Herb and Sarah and the Purdue
Borane Research Fund. Even though HCB provided the Iunding,
it was a well-deserved honor Ior Herb to be the Iirst recipient.
The Iollowing year, Herb and Sarah endowed the Herbert C.
Brown ProIessorship oI Chemistry at Purdue and provided all the
Iinancing to establish the Herbert C. Brown Center Ior Borane
Research at Purdue. The Iunds Ior both have come Irom past
royalty payments Irom Aldrich. Continuing royalty payments will
be used to provide Iuture Iinancial support oI these two entities.
8. ConcIusions
It is generally believed that Brown`s body oI work in boron
chemistry (the hydroboration reaction, reactions oI organoboranes,
selective reductions using boron hydrides, and asymmetric
synthesis using borane reagents) represents the single most
important individual accomplishment oI the 20th century in
synthetic chemistry. Aldrich is very proud to have played a part
in achieving this accomplishment.
In 1972, Aldrich`s motto was 'CraItsmen in Chemistry¨, which
was very appropriate Ior both HCB and the Aldrich chemists at
that time. Later, Aldrich changed its motto to 'Chemists Helping
Chemists in Research and Industry¨, which was how HCB also
approached his contributions to synthetic chemistry. He always
wanted his reagents to be used by others in their research. Today,
Aldrich`s motto is 'Advancing Science¨. There is no question
that Herbert C. Brown worked his entire liIe to advance borane
science. He will be missed, but we will continue to explore and
develop the borane chemistry he Iirst discovered.
9. Re!erences and Notes
(1) (a) Jacoby, M. Chem. Eng. News 2005, 83 (January 3), 8. (b) Perks,
B. Chem. Worla 2005, 2 (February), 10.
(2) http://www.chem.purdue.edu/hcbrown/ (accessed February 2005).
Please note especially the links to Biography, HCB Story
(autobiographical): Purdue Lecture: 1979 Nobel Prize with a
PDF Iile oI the HCB Nobel lecture oI December 8, 1979: and a
bibliographical archive listing all oI HCB`s patents (total oI 63),
publications (total ~ 1200), the 22 M.S. degree theses, and the 141
Ph.D. theses oI HCB`s Iormer students.
(3) (a) Brewster, J. H. Alarichimica Acta 1987, 20, 3. (b) Davenport,
D. A. Alarichimica Acta 1987, 20, 25. (c) Firsan, S. J. Alarichimica
Acta 2001, 34, 35. (d) Herbert C. Brown and Aldrich (Eaitors
note). Alarichimica Acta 2002, 35, 2.
(4) For a review covering this early period oI organoborane research, see
Brown, H. C. Organic Svntheses via Boranes: Wiley-Interscience:
New York, 1975. (Reprinted as Organic Svntheses via Boranes.
Jolume 1 by Aldrich Chemical Company, Inc.: Cat. No. Z40,094-7.)
(5) (a) Schlesinger, H. I.: Brown, H. C. J. Am. Chem. Soc. 1940, 62,
3429. (b) Schlesinger, H. I.: Brown, H. C.: Finholt, A. E. J. Am.
Chem. Soc. 1953, 75, 205.
(6) (a) Lane, C. F. Alarichimica Acta 1973, 6, 21. (b) Lane, C. F.
Alarichimica Acta 1973, 6, 51. (c) Lane, C. F. Alarichimica Acta
1975, 8, 3. (d) Lane, C. F. Alarichimica Acta 1975, 8, 20. (e) Lane,
C. F. Alarichimica Acta 1977, 10, 41. (I) Lane, C. F. Svnthesis 1975,
135. (g) Lane, C. F. Chem. Rev. 1976, 76, 773.
(7) (a) Brown, H. C. Alarichimica Acta 1974, 7, 43. (b) Krishnamurthy,
S. Alarichimica Acta 1974, 7, 55.
(8) (a) Brown, H. C.: Campbell, J. B., Jr. Alarichimica Acta 1981, 14,
3. (b) Srebnik, M.: Ramachandran, P. V. Alarichimica Acta 1987,
20, 9. (c) Dhar, R. K. Alarichimica Acta 1994, 27, 43. (d) Cho,
B. T. Alarichimica Acta 2002, 35, 3. (e) Ramachandran, P. V.
Alarichimica Acta 2002, 35, 23. (I) Kanth, J. V. B. Alarichimica
Acta 2002, 35, 57.
About the Author
Clinton F. Lane was born on January 29, 1944, in Iowa City,
Iowa. He received his B.S. degree in chemistry in 1966 Irom
Iowa State University oI Science and Technology and his Ph.D.
degree in 1972 Irom Purdue University, where he studied
under the direction oI ProIessor Herbert C. Brown. AIter one
year oI postdoctoral studies at Cornell University, Clint ioined
Aldrich Chemical Company as an R&D chemist with the goal
oI commercializing the organoborane technology discovered in
HCB`s laboratories. He was personally involved, or led teams, in
new-product R&D, process R&D, scale-up, market development,
and the manuIacturing oI hundreds oI boron hydride, metal
hydride, organoboron, and organometallic reagents that are now
commercially available Irom Sigma-Aldrich, Inc. In later years at
Aldrich, he was involved extensively in business development and
technology licensing. Clint led a team that negotiated and set up
a spin-oII ioint venture (Aldrich-APL, LLC): he also negotiated
the terms oI, and led the integration teams Ior, two acquisitions
(Carbolabs, Inc., and Isotec, Inc.). In recognition oI his service oI
over 30 years to the chemical community, Clint received several
awards, and eventually became President oI Aldrich in 1999. He
retired in 2003, and is presently a research proIessor at Northern
Arizona University.
Figure 4. :-Pihehe-Derived 8orahe ReagehIs.
Figure 3. RepresehIaIive LisI o! Ihe LaIesI 8orahe ReagehIs.
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Re!erences. (!) Yu, J.-O. el al. Chem Commun. 2003, 678. (2) 8remeyer, N. el al. 5vn|e|| 2002,
!843. (3) Ley, S. V. el al. Chem Commun. 2002, !!34. (4) Chandrashekar, P. el al. Chem Commun.
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49
V
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OutIine
1. Introduction
2. Preparation oI Potassium OrganotriIluoroborates
3. Suzuki Cross-Coupling Reactions
3.1. AlkyltriIluoroborates
3.2. AryltriIluoroborates
3.3. HeteroaryltriIluoroborates
3.4. AlkenyltriIluoroborates
3.5. AlkynyltriIluoroborates
3.6. Synthetic Application
4. Oxidation Reactions
4.1. Epoxidation
4.2. Ozonolysis
5. Conclusions
6. ReIerences and Notes
1. Introduction
Boronic acids, boronate esters, and organoboranes have been
employed Ior many years as the principal organoboron partners in
SuzukiMiyaura-type cross-coupling reactions.
1
However, these
reagents possess many limitations. Boronic acids are notorious Ior
being diIIicult to puriIy and Ior having an uncertain stoichiometry.
Even though the use oI boronate esters is more attractive Irom this
point oI view, these reagents lack atom economy and are more
expensive to employ. Organoboranes are limited by the inherent
characteristics oI the in situ hydroboration reaction used to create
them. These latter reagents also suIIer Irom high sensitivity to
air and poor Iunctional-group compatibility in some cases. In
contrast, organotriIluoroborates are unique compounds that have
been shown to overcome these limitations. These reagents can
be easily prepared Irom inexpensive materials. They are stable
to air and moisture, allowing storage Ior long periods oI time
without noticeable degradation. In Iact, their high versatility and
stability has made them excellent partners in SuzukiMiyaura-
type coupling reactions.
Even though the chemistry oI organotriIluoroborates has
been comprehensively reviewed elsewhere,
2
the recent growth
in the application oI these compounds warrants another
look. The present review outlines the utility and versatility oI
organotriIluoroborates in cross-coupling reactions. Additionally,
the ability oI these reagents to resist chemical oxidation will be
highlighted. This Ieature oI organotriIluoroborates oIIers a unique
opportunity to preserve the carbonboron bond in the oxidation oI
remote Iunctionality within the same molecule.
2. Preparation o! Potassium Organotri!Iuoroborates
Although potassium organotriIluoroborates have been known Ior
some time, Vedeis and co-workers were the Iirst to report the
most convenient synthesis oI these materials Irom boronic acids
and derivatives utilizing the readily available and inexpensive
KHF
2
.
3
In combination with this Iacile process, potassium
organotriIluoroborates are thus accessed by two general methods
(Scheme 1).
36
They can be readily prepared by starting with
the transmetalation oI organolithium or Grignard reagents with
trialkylborates.
4
Alternatively, they can be synthesized ultimately
by various catalyzed or uncatalyzed hydroborations oI alkynes or
alkenes,
5,6
taking advantage oI the unique selectivity associated
with each version oI this process.
3. 5uzuki Cross-CoupIing Reactions
Early studies by the groups oI Genêt
7
and Xia
8
demonstrated
the potential oI organotriIluoroborates in palladium-catalyzed
coupling reactions to Iorm biaryls using arenediazonium salts
or diaryliodonium salts as electrophiles. It should be noted that
organotriI luoroborates led to superior yields and reactivity
in side-by-side comparisons with boronic acids.
9
Since those
early studies, the scope oI cross-coupling reactions that utilize
organotriIluoroborates has expanded considerably.
3.1. Alkyltrifluoroborates
The Iirst cross-coupling reactions oI alkyltriIluoroborates with
aryl halides were eIIiciently perIormed using PdCl
2
(ddpI) as the
catalyst, Cs
2
CO
3
as the base, and THFH
2
O as the solvent system,
and showed tolerance oI a number oI Iunctional groups (eq 1).
10,11

OrganotriHuoroborates:
Expanding Organoboron Chemistry
Garv A. Molanaer* ana Ruth Figueroa
Rov ana Diana Jagelos Laboratories
Department of Chemistrv
Universitv of Pennsvlvania
231 South 34th Street
Philaaelphia. PA 19104-6323. USA
Email. gmolanar(sas.upenn.eau
Dr. Gary A. Molander Dr. Ruth Figueroa
50
O
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r
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r
o
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o
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a
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5
Aryl halides are attractive partners because oI their ready
availability and economy. Interestingly, the presence oI water is
essential Ior the eIIiciency oI the reaction. This requirement Ior
water and added base has elicited several mechanistic studies on
the actual species involved in the coupling process.
12,13
Aryl triIlates, common coupling partners in palladium-
catalyzed cross-coupling reactions, were as eIIicient as the aryl
halides (eq 2).
10,11
Surprisingly, the nitro group survived the basic
reaction conditions, when p-nitrophenyl triIlate was reacted with
potassium benzyltriIluoroborate. By contrast, the nitro group is
reduced to the corresponding aniline product in Suzuki reactions
with B-alkyl-9-BBN.
14
The electrophiles employed showed the
same relative reactivity order as that observed with organotin
15

and B-alkyl-9-BBN
14
reagents, i.e., Br ~ OTI ~~ Cl (eq 3).
10

The use oI secondary alkyltriIluoroborates was prohibited by
the predominance oI B-elimination and dehydroboronation
pathways.
3.2. Aryltrifluoroborates
The use oI aryltriIluoroborates in Suzuki-type reactions was Iirst
reported by Genêt`s and Xia`s groups. Genêt and co-workers
7

reported the reaction oI arenediazonium tetraIluoroborates with
aryltriIluoroborates using two catalyst systems: Pd(OAc)
2
in 1,4-
dioxane (A) and Pd
2
(µ-OAc)
2
|P(o-tolyl)
3
|
2
in MeOH (B) (eq 4).
7a

These systems were tolerant oI diIIerent Iunctional groups and, in
the case oI the ortho-chloro-substituted aryltriIluoroborate, only
conditions B were eIIicient due to the precipitation oI metallic
palladium when using conditions A. The reaction was also
chemoselective toward the arenediazonium salt in the presence
oI halides or triIlates.
Chen and Xia also reported the use oI diaryliodonium salts (eq 5)
and 2-thienyl(tosyloxy)iodobenzene (eq 6) as coupling partners oI
organotriIluoroborates to provide biaryls in excellent yields.
8
The
scope oI the reaction was extended to palladium catalysts with
or without phosphine ligands. Similar results were obtained with
Koser`s reagent, PhI(OH)OTs, as the coupling partner.
Subsequently, the reaction oI aryltriIluoroborates with aryl
halides as coupling partners was developed (eq 7).
12,16
SpeciIically,
a key point was the discovery that the use oI a base was required.
As previously observed by Xia, many oI the reactions could be
perIormed under ligandless conditions. A variety oI triIluoroborates
were reacted using Pd(OAc)
2
as the catalyst and inexpensive
K
2
CO
3
as the base. The choice oI solvent Ior these cross-
couplings was critical because oI solubility issues associated with
triIluoroborates. Another added Ieature oI these reactions was their
insensitivity to oxygen: excellent results were obtained whether
the reactions were carried out in an inert atmosphere or in the air.
The coupling oI potassium phenyltriIluoroborate with a variety
oI electron-rich aryl halides aIIorded the corresponding biaryls in
good-to-excellent yields. The slight decrease in yield using amide
or amine substituents might be due to their complexation with the
palladium catalyst.
17
The reaction oI 4-bromobenzonitrile (an electron-poor
aryl bromide) with electron-deIicient aryltriIluoroborates also
aIIorded excellent yields (eq 8).
12
The reaction oI 2,6-diIluoro-
and pentaIluorophenyltriIluoroborate (and electron-deIicient
organoboron partners in general) revealed an inherent advantage oI
the organotriIluoroborates. In both oI these cases, the corresponding
boronic acids have Iailed to couple under a variety oI diIIerent
reaction conditions owing to competitive protodeboronation.
12,18
The reaction oI ortho-substituted aryltriIluoroborates and aryl
bromides required longer reaction times, revealing the inhibitory
eIIects oI steric hindrance (Scheme 2).
12
In the case oI the halide
eq 3
eq 4
5cheme 1. 1he 1wo Ceheral MeIhods
!or Preparihg OrgahoIri!luoroboraIes.
eq 1
eq 2
5!
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.

3
8
,

N
O
.

2

º

2
0
0
5
partner, very hindered substrates are not well tolerated. For
example, the reaction oI 4-methoxyphenyltriIluoroborate with
2-bromomesitylene produced the coupled product in only a 52°
yield. Homocoupling oI the triIluoroborate was a competing
pathway. Hindered aryltriIluoroborates are more readily coupled
with aryl halide partners.
The Suzuki-type cross-coupling oI heteroaryl bromides
aIIorded the biaryls in modest-to-excellent yields (eq 9).
12
The
reaction between 1-phenyltriIluoroborate with 2-bromopyridine
did not proceed to completion, presumably due to complexation
oI the nitrogen moiety to the catalyst.
17
Longer reaction times only
increased the homocoupling oI the triIluoroborate. Dependence
on the reactivity oI the substrate was demonstrated, when higher
yields were observed as in the case oI the acyl-substituted
thiophene and Iuran. Reactions with the more sterically hindered
1-naphthyltriIluoroborate were also high-yielding. In Iact, the
eIIective reaction with 2-chloropyrazine represented another
example wherein triIluoroborates display improved reactivity over
analogous boronic acids.
Batey and Quach showed that tetrabutylammonium
triIluoroborates, which are more soluble in organic solvents than
the potassium salts, can also be used in cross-coupling reactions
using ligand-added conditions (eq 10).
13

3.3. Heteroaryltrifluoroborates
The Suzuki-type reactions were expanded to the use oI hetero-
aryltriIluoroborates and a number oI diverse heteroaryl bromides
as coupling partners (eq 11).
12
Activated heteroaryl halides
such as 3-bromopyridine require a shorter reaction time than
2-bromopyridine. These heteroaryl halides also reacted under
ligandless conditions. Unactivated thiophenes and thiazoles
required longer reaction times and the use oI PdCl
2
(dppI)·CH
2
Cl
2
.
In some cases, this led to homocoupling oI the triIluoroborate.
It is oI interest that reaction oI the unprotected 7-bromoindole
gave 77° oI the expected biaryl. It is believed in this case that
the basic, ligand-added conditions inhibited complexation oI the
indole nitrogen to the palladium.
12
The cross-coupling oI tetrabutylammonium thien-3-
yltriIluoroborate with 4-bromoacetophenone has also been
accomplished in 91° yield.
13
3.4. Alkenyltrifluoroborates
AlkenyltriIluoroborates are exceptional partners in the Suzuki
cross-coupling reaction, providing advantages over other
organoboron counterparts. Although alkenyldialkylboranes are
eIIicient substrates in this reaction,
19
their high molecular weight
and the requirement to remove the two 'dummy¨ groups on the
boron make them less atom-economical. Lower molecular weight
alkenylboronic acids, such as vinyl and propenylboronic acids,
20

readily polymerize and cannot be easily isolated.
Initial studies with Iunctionalized aryl electrophiles demonstrated
that the coupling reaction using PdCl
2
(dppI)·CH
2
Cl
2
could be
accomplished using both halides and triIlates (eq 12).
21,22
The
reactions were run in i-PrOHH
2
O using t-BuNH
2
as the inexpensive
base. It is important to mention that the conditions developed Ior
the coupling oI alkyltriIluoroborates |PdCl
2
(dppI)·CH
2
Cl
2
, Cs
2
CO
3
,
THFH
2
O| were also eIIicient. A variety oI Iunctional groups
(e.g., nitro, cyano, aldehyde, ketone, ether) were tolerated in these
reactions. The reactions were eIIicient with variously substituted
alkenyltriIluoroborates, Irom the parent vinyltriIluoroborate to
trisubstituted analogs (eq 13).
22
The double-bond geometry oI the
triIluoroborate was retained with complete stereospeciIicity in these
reactions. Batey and Quach have reported that tetrabutylammonium
eq 5
eq 6
eq 7
eq 8
5cheme 2. L!!ecI o! SIeric Hihdrahce
ih ArylIri!luoroboraIe Couplihg ReacIiohs.
52
O
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.

3
8
,

N
O
.

2

º

2
0
0
5
octen-1-yltriIluoroborate reacts readily with 4-bromoacetophenone
to give the coupling product in 87° yield.
13
The cross-coupling reaction oI alkenyltriIluoroborates has been
extended to heteroaryl bromides (eq 14)
22
and, as mentioned above,
cross-coupling reactions using potassium vinyltriIluoroborate are
particularly important (eq 15).
22
In contrast to its boronic acid
and boronate ester counterparts, potassium vinyltriIluoroborate
can be prepared in large quantities and stored indeIinitely.
20

Cross-coupling oI alkenyltriIluoroborates with alkenyl halides
results in the preparation oI coniugated dienes which are important
synthetic units. Coniugated dienes are present in many biologically
active compounds, and serve as starting materials in the highly
useIul DielsAlder reaction. Although many other methods oI
synthesis oI coniugated dienes are available, these have many
limitations. The Kumada
23
and Negishi
24
coupling reactions
sometimes provide low chemoselectivities and yields, and oIten
create operational diIIiculties as well. For example, both are air-
sensitive and the starting materials are usually prepared in situ.
The tin reagents utilized in the Stille coupling are toxic, and the
tin-containing byproducts Iormed in the coupling are diIIicult to
remove. Some oI the limitations oI alkenylboronic acid derivatives
have been mentioned above. Additionally, the added requirement
oI having to use excess amounts oI toxic thallium bases to achieve
eIIiciency in cross-coupling reactions oI alkenylboronic acids
and alkenylboronate esters with alkenyl halides Iurther limits the
useIulness oI these organoboron reagents.
25
The Suzuki-type reactions oI alkenyltriIluoroborates with
alkenyl halides were perIormed using optimized conditions
|Pd(OAc)
2
, 2 PPh
3
, Cs
2
CO
3
, THFH
2
O| (eq 16).
26
The system
was sensitive to air and thus inert atmosphere conditions were
required. Initial studies revealed that the process is completely
stereospeciIic. Thus, the reaction oI (E)- and (Z)-4-phenyl-1-
buten-1-yltriIluoroborate with (E)- and (Z)-1-bromo-5-chloro-
1-pentene resulted in the synthesis oI the Iour possible isomers
in a stereodeIined manner (~99°). Interestingly, the reaction
was not susceptible to steric hindrance within the halide partner.
Highly substituted alkenyl bromides aIIorded the dienes in
high yields. Additionally, many Iunctional groups (e.g., Iormyl
and cyano) were tolerated.
26
In particular, the reaction with 2-
bromo-3-methyl-2-cyclopenten-1-one was oI interest, because
A-bromoenones were previously Iound to be unreactive under
other coupling conditions.
27
The triIluoroborate counterpart was similarly versatile with
regard to steric and Iunctional-group tolerance (eq 17).
26
A
special case is the reaction oI the triIluoroborate bearing a methyl
ester with 3-bromo-3-buten-1-ol. Under the reaction conditions
developed, hydrolysis oI the ester and/or transesteriIication might
be expected, but neither was observed. This has been attributed to
the use oI a heterogeneous base.
28

The synthesis oI diene Iunctionalities incorporated within
many natural products oIten involves the use oI various silyl
protecting groups along the way. ThereIore, the compatibility oI
the silyl protecting group with organotriIluoroborates, an obvious
source oI Iluoride, was also evaluated (eq 18).
26
Somewhat
surprisingly, dienes were obtained in high yields with the silyl
ether groups surviving the reaction conditions intact.
26
3.5. Alkynyltrifluoroborates
The reaction oI potassium alkynyltriIluoroborates with aryl
halides and triIlates complements the usual Sonogashira coupling
reaction.
29
Other organoboron compounds have been used in
similar coupling reactions, but many limitations are associated
with their use.
3032
Genêt was the Iirst to attempt the cross-coupling
eq 11
eq 9
eq 10
eq 12
53
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.

3
8
,

N
O
.

2

º

2
0
0
5
oI potassium alkynyltriIluoroborates with arenediazonium salts.
7

However, the maior reaction pathway in this case was simple
reduction oI the diazonium salts.
Subsequently, a successIul protocol Ior the Suzuki cross-
coupling oI potassium alkynyltriIluoroborates with the more
accessible aryl halides and triIlates was developed. Thus, the cross-
coupling reaction oI potassium 1-hexyn-1-yltriIluoroborate, using
PdCl
2
(dppI)·CH
2
Cl
2
as the catalyst, with various aryl bromides
proceeded in good yields (eq 19).
33
Surprisingly, alcohols and
carboxylic acids were tolerated in the reaction, even though, in
principle, protodeboronation oI the alkynyltriIluoroborate with
these Iunctional groups is a distinct possibility.
2,12,34
Heteroaryl
bromides were also eIIective coupling partners.
The reaction was expanded to the use oI aryl triIlates.
33
Moderate-
to-excellent yields were obtained with both electron-deIicient and
electron-rich triIlates. In addition, a number oI diversely substituted
alkynyltriIluoroborates were also evaluated (eq 20).
33
SatisIactory-to-
excellent yields were observed, even in the presence oI silyl ethers,
which are normally quite labile in the presence oI Iluoride ions.
3.6. Synthetic Application
The Iirst application oI organotriIluoroborates in natural product
synthesis was demonstrated in the Iormal total synthesis oI
oximidine II.
35
Oximidines are natural products with a diverse
biological activity.
36
The challenge in these targets was the
construction oI the highly strained macrolide. The key step in this
synthesis was the macrocyclization oI an alkenyltriIluoroborate to
accomplish the Iormation oI the 12-membered ring (Scheme 3).
35

The reaction was perIormed under previously developed Suzuki-
type reaction conditions as discussed above. This approach
aIIorded several advantages over traditional macrolactonization
reactions that had been attempted previously, and its success was
due to the ease oI access oI the triIluoroborate Iunctionality via the
Snieckus hydroboration
37
and the inherent stability oI the resulting
boron derivative.
4. Oxidation Reactions
Organoboron compounds are generally incompatible with
oxidants, which readily cleave the labile carbonboron bond.
38

OrganotriIluoroborates can be utilized to overcome this limitation.
The Iirst indication oI this unexpected stability was the oxidation oI
thioether 1 to sulIone 2 using m-CPBA (eq 21).
39
Both the oxidative
strength oI the peracid and the acidity oI the resulting carboxylic
acid byproduct were well tolerated in this process.
4.1. £poxidation
Organot ri Il uoroborat es have been epoxi di zed usi ng
dimethyldioxirane (eq 22).
39
The scope oI the reaction was
demonstrated by the use oI a variety oI alkenes bearing the
triIluoroborate unit. The remarkable stability oI the product as
compared with the highly reactive oxiranyl anions was attributed
to two Iactors: (i) A-elimination was inhibited by the covalent
nature oI the carbonboron bond, and (ii) the strength oI the boron
Iluorine bond prevents hydrolysis oI the boron species and provides
resistance also to oxidation and A-transIer reactions.
2a,2c,40,41
EpoxytriIluoroborates are promising substrates in Suzuki-
type reactions. The reaction conditions Ior the coupling can be
manipulated to achieve preservation oI the oxirane ring or its
opening (Scheme 4).
39
4.2. Ozonolysis
Ozonolysis oI organotriIluoroborates has also been a part oI
ongoing studies oI the oxidation oI these substrates. These studies
eq 14
eq 13
eq 16
eq 15
eq 17
54
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L
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O
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C
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V
O
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.

3
8
,

N
O
.

2

º

2
0
0
5
eq 19
eq 18
eq 20
eq 21
5cheme 3. Formal 1oIal SyhIhesis o! Oximidihe II.
eq 22
5cheme 5. 1he CompaIibiliIy o! 1ri!luoroboraIes
wiIh Ozoholysis CohdiIiohs.
5cheme 4. ReacIioh CohdiIiohs !or Ihe ReIehIioh
ahd Opehihg o! Ihe Oxirahe Rihg ih Ihe Suzuki-1ype
Cross-Couplihg ReacIioh.
55
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.

3
8
,

N
O
.

2

º

2
0
0
5
have shown that potassium triIluoroborates are stable to strong
oxidative conditions. For example, the oxidation oI the alkene
Iunctionality in unsaturated alkyl- or aryltriIluoroborates has
been accomplished by bubbling ozone through an acetonewater
or acetonedichloromethane solution. The resulting ozonides
were reduced using either dimethyl sulIide or zinc in acetic acid
to provide the expected carbonyl groups, while preserving the
triIluoroborate unit.
42
Ozonolysis oI the carboncarbon double
bonds in unsaturated tetrabutylammonium triIluoroborates takes
place iust as readily and produces the corresponding aldehydes
and ketones in excellent yields (Scheme 5).
42
5. ConcIusions
OrganotriIluoroborates are a unique class oI organoboron
compounds that have emerged as promising synthetic
reagents. Their easy access and inherent stability has led to the
accomplishment oI diverse and challenging SuzukiMiyaura-type
reactions. Their remarkable behavior toward oxidative conditions
has resulted in the development oI unprecedented epoxidation and
ozonolysis reactions. ThereIore, organotriIluoroborates are able
to overcome many limitations associated with the use oI boronic
acids or boronate esters, thereby expanding the role oI organoboron
compounds in selective organic synthesis.
6. Re!erences and Notes
(1) For recent reviews oI the SuzukiMiyaura cross-coupling, see: (a)
Miyaura, N.: Suzuki, A. Chem. Rev. 1995, 95, 2457. (b) Suzuki,
A. J. Organomet. Chem. 1999, 576, 147. (c) Suzuki, A. In Metal-
Catalvzea Cross-Coupling Reactions: Diederich, F., Stang, P. J.,
Eds.: Wiley-VCH: Weinheim, 1998: pp 4997.
(2) Darses, S.: Genêt, J.-P. Eur. J. Org. Chem. 2003, 4313.
(3) (a) Vedeis, E.: Chapman, R. W.: Fields, S. C.: Lin, S.: SchrimpI,
M. R. J. Org. Chem. 1995, 60, 3020. (b) Vedeis, E.: Fields, S. C.:
Hayashi, R.: Hitchcock, S. R.: Powell, D. R.: SchrimpI, M. R. J.
Am. Chem. Soc. 1999, 121, 2460.
(4) Matteson, D. S. Tetrahearon 1989, 45, 1859.
(5) Brown, H. C.: Bhat, N. G.: Somayaii, V. Organometallics 1983, 2,
1311.
(6) (a) Burgess, K.: Ohlmeyer, M. J. Chem. Rev. 1991, 91, 1179. (b)
Pereira, S.: Srebnik, M. J. Am. Chem. Soc. 1996, 118, 909. (c) Kabalka,
G. W.: Narayana, C.: Reddy, N. K. Svnth. Commun. 1994, 24, 1019.
(d) Männig, D.: Nöth, H. Angew. Chem.. Int. Ea. Engl. 1985, 24, 878.
(e) Garrett, C. E.: Fu, G. C. J. Org. Chem. 1996, 61, 3224.
(7) (a) Darses, S.: Genêt, J.-P.: Brayer, J.-L.: Demoute, J.-P. Tetrahearon
Lett. 1997, 38, 4393. (b) Darses, S.: Michaud, G.: Genêt, J.-P. Eur.
J. Org. Chem. 1999, 1875.
(8) Chen, Z.-C.: Xia, M. Svnth. Commun. 1999, 29, 2457.
(9) (a) Batey, R. A.: Thadani, A. N.: Smil, D. V.: Lough, A. J. Svnthesis
2000, 990. (b) Batey, R. A.: Thadani, A. N.: Smil, D. V. Org.
Lett. 1999, 1, 1683. (c) Batey, R. A.: Thadani, A. N.: Smil, D. V.
Tetrahearon Lett. 1999, 40, 4289.
(10) Molander, G. A.: Ito, T. Org. Lett. 2001, 3, 393.
(11) Molander, G. A.: Yun, C.-S.: Ribagorda, M.: Biolatto, B. J. Org.
Chem. 2003, 68, 5534.
(12) Molander, G. A.: Biolatto, B. J. Org. Chem. 2003, 68, 4302.
(13) Batey, R. A.: Quach, T. D. Tetrahearon Lett. 2001, 42, 9099.
(14) Oh-e, T.: Miyaura, N.: Suzuki, A. Svnlett 1990, 221.
(15) (a) Scott, W. J.: Stille, J. K. J. Am. Chem. Soc. 1986, 108, 3033. (b)
Echavarren, A. M.: Stille, J. K. J. Am. Chem. Soc. 1987, 109, 5478.
(16) Molander, G. A.: Biolatto, B. Org. Lett. 2002, 4, 1867.
(17) Yin, J.: Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 12051.
(18) Thiemann, T.: Umeno, K.: Ohira, D.: Inohae, E.: Sawada, T.:
Mataka, S. New J. Chem. 1999, 1067.
(19) (a) Miyaura, N. Top. Curr. Chem. 2002, 219, 32. (b) Miyaura, N.:
Satoh, M.: Suzuki, A. Tetrahearon Lett. 1986, 27, 3745. (c) Suzuki,
A.: Brown, H. C. Suzuki Coupling: Organic Syntheses via Boranes,
Volume 3: Aldrich Chemical Company: Milwaukee, 2003: p 37.
(20) Matteson, D. S. J. Am. Chem. Soc. 1960, 82, 4228.
(21) Molander, G. A.: Rivero, M. R. Org. Lett. 2002, 4, 107.
(22) Molander, G. A.: Bernardi, C. R. J. Org. Chem. 2002, 67, 8424.
(23) Huo, S.: Negishi, E. In Hanabook of Organopallaaium Chemistrv
for Organic Svnthesis: Negishi, E., de Meiiere, A., Eds.: Wiley-
Interscience: New York, 2002: Vol. 1, pp 335409.
(24) (a) Negishi, E.: Ay, M.: Gulevich, Y. V.: Noda, Y. Tetrahearon Lett.
1993, 34, 1437. (b) Zhu, L.: Wehmeyer, R. M.: Rieke, R. D. J. Org.
Chem. 1991, 56, 1445. (c) DuIIault, J.-M.: Einhorn, J.: Alexakis, A.
Tetrahearon Lett. 1991, 32, 3701. (d) Lipshutz, B. H.: Lindsley, C.
J. Am. Chem. Soc. 1997, 119, 4555.
(25) (a) Armstrong, R. W.: Beau, J.-M.: Cheon, S. H.: Christ, W. J.:
Fuiioka, H.: Ham, W.-H.: Hawkins, L. D.: Jin, H.: Kang, S. H.:
Kishi, Y.: Martinelli, M. J.: McWhorter, W. W., Jr.: Mizuno, M.:
Nakata, M.: Stutz, A. E.: Talamas, F. X.: Taniguchi, M.: Tino, J.
A.: Ueda, K.: Uenishi, J.: White, J. B.: Yonaga, M. J. Am. Chem.
Soc. 1989, 111, 7525. (b) Kobayashi, S.: Mori, K.: Wakabayashi, T.:
Yasuda, S.: Hanada, K. J. Org. Chem. 2001, 66, 5580. (c) Scheidt, K.
A.: Bannister, T. D.: Tasaka, A.: Wendt, M. D.: Savall, B. M.: Fegley,
G. J.: Roush, W. R. J. Am. Chem. Soc. 2002, 124, 6981. (d) Pazos,
Y.: Iglesias, B.: de Lera, A. R. J. Org. Chem. 2001, 66, 8483. (e)
Mergott, D. J.: Frank, S. A.: Roush, W. R. Org. Lett. 2002, 4, 3157.
(26) Molander, G. A: Felix, L. A. J. Org. Chem. 2005, in press.
(27) (a) Negishi, E.: Owczarczyk, Z. R.: Swanson, D. R. Tetrahearon
Lett. 1991, 32, 4453. (b) Lee, J.: Snyder, J. K. J. Org. Chem.
1990, 55, 4995. (c) Malleron, J. L.: Bacqué, E.: Desmazeau, P.:
M`Houmadi, C.: Paris, J. M.: Peyronel, J. F. Svnth. Commun. 1995,
25, 2355.
(28) The reaction using t-BuNH
2
as the base gave only 33° oI the
product owing to hydrolysis oI the ester group.
(29) (a) Campbell, I. In Organocopper Reagents. A Practical Approach:
Taylor, R. J. K., Ed.: OxIord University Press: OxIord, 1994: p 217.
(b) Sonogashira, K. In Comprehensive Organic Svnthesis: Trost, B.
M., Ed.: Pergamon: OxIord, 1991: Vol. 3, p 521. (c) Farina, V. In
Transition Metal Organometallics in Organic Svnthesis: Hegedus,
L. S., Ed.: Comprehensive Organometallic Chemistry II Series:
Pergamon: OxIord 1995: Vol. 12, p 222. (d) Miyaura, N. In Cross-
Coupling Reactions. A Practical Guiae: Miyaura, N., Ed.: Springer-
Verlag: New York, 2002.
(30) Soderquist, J. A.: Matos, K.: Rane, A.: Ramos, J. Tetrahearon Lett.
1995, 36, 2401.
(31) Fürstner, A.: Seidel, G. Tetrahearon 1995, 51, 11165.
(32) Castanet, A.-S.: Colobert, F.: Schlama, T. Org. Lett. 2000, 2, 3559.
(33) Molander, G. A.: Katona, B. W.: Machrouhi, F. J. Org. Chem. 2002,
67, 8416.
(34) (a) Suzuki, A. Pure Appl. Chem. 1994, 66, 213. (b) Suzuki, A. Pure
Appl. Chem. 1991, 63, 419. (c) Suzuki, A. Acc. Chem. Res. 1982,
15, 178.
(35) Molander, G. A.: Dehmel, F. J. Am. Chem. Soc. 2004, 126, 10313.
(36) Yet, L. Chem. Rev. 2003, 103, 4283.
(37) Kalinin, A. V.: Scherer, S.: Snieckus, V. Angew. Chem.. Int. Ea.
2003, 42, 3399.
(38) (a) Johnson, J. R.: Van Campen, M. G., Jr. J. Am. Chem. Soc. 1938, 60,
121. (b) Matteson, D. S.: Moody, R. J. J. Org. Chem. 1980, 45, 1091.
(39) Molander, G. A.: Ribagorda, M. J. Am. Chem. Soc. 2003, 125,
11148.
(40) (a) Cragg, G. M. Organoboranes in Organic Svnthesis: Marcel
Dekker: New York, 1973. (b) Brown, H. C. Organic Svntheses
via Boranes: Wiley-Interscience: New York, 1975. (Reprinted as
56
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Organic Svntheses via Boranes. Jolume 1 by Aldrich Chemical
Company, Inc.: Cat. No. Z40,094-7.)
(41) (a) Brown, H. C.: Zaidlewicz, M. Organic Svntheses via Boranes
Jolume 2: Aldrich Chemical Company: Milwaukee, 2001. (b) Roush,
W. R. In Comprehensive Organic Svnthesis: Trost, B. M., Fleming,
I., Heathcock, C. H., Eds.: Pergamon: OxIord, 1991: pp 153. (c)
Matteson, D. S. Stereoairectea Svnthesis with Organoboranes:
Springer-Verlag: Berlin, 1995. (d) Yamamoto, Y.: Asao, N. Chem.
Rev. 1993, 93, 2207. (e) Ollivier, C.: Renaud, P. Chem. Rev. 2001,
101, 3415. (I) Fagnou, K.: Lautens, M. Chem. Rev. 2003, 103, 169.
(42) Molander, G. A.: Cooper, D. G. University oI Pennsylvania,
Philadelphia, PA. Unpublished work, 2005.
About the Authors
Gary Molander was born in Cedar Rapids, Iowa. He received
his B.S. degree at Iowa State University in 1975, working with
ProIessor Richard C. Larock. He entered the graduate chemistry
program at Purdue University in 1975, obtaining his Ph.D. degree
in 1979 under the direction oI ProIessor Herbert C. Brown. In
1980, he ioined ProIessor Barry Trost`s group at the University
oI Wisconsin, Madison, as a National Institutes oI Health
postdoctoral Iellow and, in 1981, he accepted an appointment at
the University oI Colorado, Boulder, as an assistant proIessor oI
chemistry. He was promoted to associate proIessor in 1988 and
proIessor oI chemistry in 1990. In 1999, he ioined the Iaculty at
the University oI Pennsylvania and, in 2001, was appointed Allan
Day ProIessor oI Chemistry.
ProIessor Molander`s research interests center on the
development oI new methods Ior organic synthesis and natural
product synthesis. A maior Iocus oI his research has been the
application oI organolanthanide reagents and catalysts to selective
organic synthesis. To date, more than 170 research papers have
emanated Irom his research program. He has received several
honors Ior his work, including an AlIred P. Sloan Foundation
Fellowship (1987), the American Cyanamid Academic Award
(1989), the Arthur C. Cope Scholar Award Irom the American
Chemical Society (ACS) in 1998, a Japanese Society Ior the
Promotion oI Science Fellowship (2002), and the Philadelphia
Section Award oI the ACS (2003). He has been a Visiting
ProIessor at the Université de Paris-Sud, Orsay, France (1989,
1997): Philipps Universität, Marburg, Germany (1989): Ecole
Supérieure de Physique et de Chimie Industrielles de Paris (1993):
Universidade Federal da Paraiba, Brazil (1998): Universidade
Federal de Pernambuco, Brazil (1998): Universidad Nacional del
Litoral, Santa Fe, Argentina (1998): Institute oI Organometallic
Chemistry, Russian Academy oI Sciences, Nizhny Novgorod,
Russia (1998): the Institut de Recherche en Chimie Organique
Fine, Rouen, France (1999), and the Universidade Federal de
Santa Maria, Brazil (2001).
He has served on the NIH Medicinal Chemistry Study Section
and the ACS Division oI Organic Chemistry Executive Committee.
In 2001, he was the Executive Director Ior the 37th National
Organic Symposium, and currently serves as the Secretary
Treasurer oI the Organic Division oI the ACS. He has been on
the editorial advisory boards oI Organometallics, Tetrahearon,
Tetrahearon Letters, and Current Topics in Meaicinal Chemistrv,
and is currently an associate editor oI Organic Letters.
Ruth Figueroa obtained her B.S. degree in industrial
chemistry Irom the University oI Puerto Rico. She received her
Ph.D. degree in organic chemistry at The Ohio State University
under the supervision oI Dr. David J. Hart. Her studies were
directed toward the synthesis oI the tetrahydropyran rings oI the
natural product lasonolide A. She ioined ProIessor Molander`s
research group in October 2004 as a postdoctoral research
associate, and is currently engaged in ongoing studies related to
the oxidation oI organotriIluoroborates.
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New Tr¡Nuoroborate Salts for Suzuk¡ Coupl¡ng
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Potassium vinyItri!Iuoroborate, 95%
65,522-8 ! g S24.00
5 g 80.00
Potassium 5-methyI-2-thiophenetri!Iuoroborate
65,494-9 ! g S27.00
5 g 90.00
Potassium 4-tert-butyIphenyItri!Iuoroborate, 95%
65,472-8 ! g S!4.50
!0 g 8!.00
Potassium 2-methoxyphenyItri!Iuoroborate
65,493-0 ! g S27.00
5 g 90.00
Potassium 2-naphthaIenetri!Iuoroborate
65,701-8 ! g S27.00
5 g 90.00
Potassium 2,4-di!IuorophenyItri!Iuoroborate
65,699-2 ! g S27.00
5 g 90.00
Trilluoroborales are air-slable allernalives lo boronic acids in palladium-calalyzed SuzukiMiyaura cross-coupling reaclions.
!,2

They are more robusl, easier lo handle, and less prone lo prolodeboronalion.
!
They display a remarkably unilorm behavior.
2

(!) Molander, C. A., 8iolallo, 8. I. Orq. Chem. 2003, 63, 4302. (2) Molander, C. A. el al. I. Orq. Chem. 2003, 68, 5534.
lor addilional inlormalion, please conlacl cdavis!@sial.com.
For compeIiIive quoIes oh larger quahIiIies, cohIacI safcglobal.com.
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3-(ßoc-aminomethyI)piperidine, 95%
65,389-6 ! g S!8.00
C
!!
H
22
N
2
O
2
!0 g 99.50
3-(ßoc-amino)pyridine, 97%
65,550-3 ! g S23.00
C
!0
H
!4
N
2
O
2
!0 g !25.00
MethyI 3-(4-morphoIino)benzoate, 97%
65,470-1 ! g S28.00
C
!2
H
!5
NO
3
5 g 96.00
MethyI 4-(cyanomethyI)benzoate, 96%
65,559-7 5 g S!5.50
C
!0
H
9
NO
2
25 g 55.00
2,3,5,6-TetramethyIbenzoic acid
56,501-6 5 g S4!.60
C
!!
H
!4
O
2
Dibenzo!uran-4-carboxyIic acid, 97%
56,283-1 ! g S3!.50
C
!3
H
8
O
3
2,3,5,6-TetramethyIbenzaIdehyde
56,500-8 5 g S9!.00
C
!!
H
!4
O
4-(4-fIuorophenyI)benzonitriIe, 97%
64,992-9 ! g S39.00
C
!3
H
8
lN 5 g !!2.00
N-MethyI-4-tri!IuoromethyIaniIine, 97%
63,105-1 ! g S27.00
C
8
H
8
l
3
N 5 g 95.40
3,6-Dibromo-2-!IuorobenzaIdehyde
65,239-3 ! g S36.00
C
7
H
3
8r
2
lO 5 g !20.00
4-ßromophenethyI bromide, 96%
65,198-2 ! g S20.00
C
8
H
8
8r
2
!0 g !!0.00
2,4-DichIorophenethyI bromide, 96%
65,382-9 ! g S25.65
C
8
H
7
8rCl
2
5 g 85.50
2-ChIorophenethyI bromide, 97%
65,501-5 ! g S2!.00
C
8
H
8
8rCl 5 g 68.90
2-MethoxyphenethyI bromide, 97%
65,503-1 ! g S25.50
C
9
H
!!
8rO 5 g 85.00
3-MethoxyphenethyI bromide, 97%
65,533-3 ! g S24.!5
C
9
H
!!
8rO 5 g 80.50
4-MethoxyphenethyI bromide, 97%
65,515-5 ! g S!9.50
C
9
H
!!
8rO 5 g 65.00
4-HydroxyphenethyI bromide, 96%
65,202-4 ! g S!7.50
C
8
H
9
8rO !0 g 96.50
3,4-DimethoxyphenethyI bromide, 97%
65,367-5 ! g S25.00
C
!0
H
!3
8rO
2
5 g 87.50
Organic Reagents and 8uilding 8locks
L E A D E R 5 H l P l N L l F E 5 C l E N C E , H l G H I E C H N O L O G Y A N D 5 E R V l C E
ALDRICH º 8OX 355 º MILWAUKLL º WISCONSIN º USA
2-(5-MethyIthien-2-yI)-4,4,5,5-tetramethyI-
1,3,2-dioxaboroIane, 95%
65,507-4 ! g S!!.00
C
!!
H
!7
8O
2
S !0 g 60.00
5-MethyI-2-thiopheneboronic acid
51,219-2 ! g S30.80
C
5
H
7
8O
2
S 5 g !24.00
2-fIuoro-3-!ormyIphenyIboronic acid
64,578-8 ! g S3!.50
C
7
H
6
8lO
3
5 g !02.00
3-ßenzyIoxy-2,6-di!IuorophenyIboronic acid
63,570-7 ! g S4!.00
C
!3
H
!!
8l
2
O
3
5 g !42.00
6-ßromo-2,3-di!IuorophenyIboronic acid
63,577-4 ! g S24.90
C
6
H
4
88rl
2
O
2
5 g 99.40
3-ßromo-5-!Iuoro-2-methoxyphenyIboronic acid
64,517-6 ! g S77.70
C
7
H
7
88rlO
3
5 g 259.50
4,5-Di!Iuoro-2-methoxyphenyIboronic acid
64,518-4 ! g S77.70
C
7
H
7
8l
2
O
3
5 g 259.50
5-ChIoro-2-propoxyphenyIboronic acid
64,519-2 ! g S3!.50
C
9
H
!2
8ClO
3
5 g !02.00
2-fIuoro-5-isopropoxyphenyIboronic acid
64,520-6 ! g S3!.50
C
9
H
!2
8lO
3
5 g !02.00
5-ßutoxy-2-!IuorophenyIboronic acid
64,523-0 ! g S3!.50
C
!0
H
!4
8lO
3
5 g !02.00
2-ßromo-4,5-di!IuorophenyIboronic acid
64,528-1 ! g S37.80
C
6
H
4
88rl
2
O
2
5 g !26.00
3-ßromo-5-methyIphenyIboronic acid
64,531-1 ! g S59.!0
C
7
H
8
88rO
2
5 g !97.00
3-formyI-5-methyIphenyIboronic acid
64,533-8 ! g S98.!0
C
8
H
9
8O
3
3-ßromo-5-!IuorophenyIboronic acid
64,534-6 ! g S!8.70
C
6
H
5
88rlO
2
!0 g !04.00
2-ßromo-3-ethoxy-6-!IuorophenyIboronic acid
64,571-0 ! g S56.20
C
8
H
9
88rlO
3
5 g !87.00
2-ßromo-6-!Iuoro-3-propoxyphenyIboronic acid
64,572-9 ! g S56.20
C
9
H
!!
88rlO
3
5 g !87.00
3-IsobutoxyphenyIboronic acid
64,573-7 ! g S3!.50
C
!0
H
!5
8O
3
5 g !02.00
2-IsobutoxyphenyIboronic acid
64,574-5 ! g S3!.50
C
!0
H
!5
8O
3
5 g !02.00
3,5-Di!ormyI-2-!IuorophenyIboronic acid
64,579-6 ! g S!34.00
C
8
H
6
8lO
4
5 g 446.00
4,5-Di!Iuoro-2-ethoxyphenyIboronic acid
65,094-3 ! g S75.00
C
8
H
9
8l
2
O
3
5 g 250.00
2,6-Di!Iuoro-3-ethoxyphenyIboronic acid
65,095-1 2 g S39.80
C
8
H
9
8l
2
O
3
!0 g !32.80
2-Isopropoxy-6-methoxyphenyIboronic acid
65,097-8 2 g S40.25
C
!0
H
!5
8O
4
!0 g !34.00
2,4-DibutoxyphenyIboronic acid
65,099-4 ! g S75.00
C
!4
H
23
8O
4
5 g 249.00
3,6-Dibromo-2-!IuorophenyIboronic acid
65,108-7 2 g S2!.50
C
6
H
4
88r
2
lO
2
!0 g 72.00
5-ßromo-3-ethoxyphenyIboronic acid
65,119-2 ! g S88.00
C
8
H
!0
88rO
3
5 g 294.00
3-(4'-HeptyIoxyphenoxymethyI)phenyI-
boronic acid
65,121-4 ! g S75.00
C
20
H
27
8O
4
5 g 249.00
2-Isobutoxy-5-methyIphenyIboronic acid
65,123-0 2 g S45.75
C
!!
H
!7
8O
3
!0 g !52.00
3-AcetyI-2-!IuorophenyIboronic acid
65,124-9 2 g S39.80
C
8
H
8
8lO
3
!0 g !32.80
8oronic Acids and £sters
1o view more hew producIs, visiI sigma-aIdrich.comlnevprod.
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Lithium dimethyIaminoborohydride soIution, 1 M in THf
65,823-5 25 mL S30.00
C
2
H
9
8LiN Li8H
3
NMe
2
!00 mL 64.00
lW 64.85
Lithium morphoIinoborohydride soIution, 1 M in THf
65,830-8 25 mL S26.00
C
4
H
!!
8LiNO Li8H
3
NP
2
(NP
2
= 4-morpholino) !00 mL 58.00
lW !06.89
Lithium pyrroIidinoborohydride soIution, 1 M in THf
65,824-3 25 mL S26.00
C
4
H
!!
8LiN Li8H
3
NP
2
(NP
2
= !-pyrrolidino) !00 mL 58.00
lW 90.89
S
igma-Aldrich is pleased lo oller a number ol lilhium
aminoborohydrides (LA8), which are readily applied
lo a range ol reduclions and aminalions.
!
LA8s are highly
reaclive yel air-slable reagenls, and liberale hydrogen
only slowly in prolic solvenls above pH 4. Developed in
lhe laboralory ol Prolessor 8aklhan Singaram al lhe
Universily ol Calilornia, Sanla Cruz, lhese new reagenls
are an allraclive and saler allernalive lo LiAlH
4
due lo
lheir seleclivily, ease ol handling, and simple workup
procedures.
!
(!) lor a broader coverage ol lhese lopics, please see lhe review
lhal slarls on lhe lacing page. Pasumansky, L., Singaram, 8.,
Coralski, C. T. A|dr|ch|m|ca Ac|a 2005, J3, 6!.
L¡th¡um Am¡noborohydr¡de lLAB) Reagents
Powerful, Air-Stable, and Selective Reducing Agents
for additionaI in!ormation about these LAßs or others that viII be avaiIabIe soon,
pIease contact our TechnicaI 5ervices department at 800-231-8327 (U5A) or at aIdrich©siaI.com.
lor inquiries aboul larger quanlilies, please conlacl us al sa!cgIobaI.com or 800-244-!!73 (USA).
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6!
V
O
L
.

3
8
,

N
O
.

2

º

2
0
0
5
Recent Advances in the Chemistry
of Lithium Aminoborohydrides
1
OutIine
1. Introduction
2. Reduction oI N-Alkyllactams and Amides
3. Reduction oI Primary Alkyl SulIonates to Hydrocarbons
4. Conversion oI Primary Alkyl MethanesulIonates to Amines
5. Tandem AminationReduction Reactions
6. Synthesis oI 2-(Dialkylamino)pyridines
7. Theoretical Calculations on LABs
8. Conclusions
9. Acknowledgements
10. ReIerences and Notes
1. Introduction
Lithium aminoborohydrides (LABs) are a new class oI powerIul,
selective, and air-stable reducing agents. LABs can be prepared
as solids or 12 M THF solutions, or can be generated in situ Ior
immediate use.
1
Since LABs can be synthesized Irom any primary
or secondary amine, the steric and electronic environments oI
these reagents can be easily controlled. Solid LAB reagents can
be used in dry air as easily as sodium borohydride, and they
maintain their chemical reactivity Ior at least 6 months when
stored at 25 °C under nitrogen or dry air. THF solutions oI LABs
retain their chemical reactivity Ior at least 9 months when stored
at 25 °C under nitrogen. LABs are capable oI reducing a variety
oI Iunctional groups (Scheme 1),
1d
and their use as reducing
agents has been the subiect oI several reviews.
2
The present
survey covers relevant research that has been published in the
past Iive years.
2. Reduction o! N-AIkyIIactams and Amides
N-Alkyllactams are reduced with 1.5 equivalents oI LiBH
3
NMe
2

in THF at 65 °C in 2 hours, aIIording the corresponding cyclic
amines in good-to-excellent yields (eq 1).
3
The method is general
Ior both Iive- and six-membered N-alkyllactams. LAB reagents
can perIorm a reagent-controlled reduction oI amides to give
either the corresponding alkanols or aminoalkanes. It is believed
that, in sterically less demanding LABs, the boron moiety
complexes the N-atom oI the amide, making it a better leaving
Lubov Pasumanskv ana Bakthan Singaram*
Department of Chemistrv ana Biochemistrv
Universitv of California. Santa Cruz
1156 High Street
Santa Cruz. CA 95064. USA
Email. singaram(chemistrv.ucsc.eau
Christian T. Goralski
CTG Consulting. LLC
Mialana. MI 48642. USA
Ms. Lubov Pasumansky Dr. Bakthan Singaram
Dr. Christian T. Goralski
62
V
O
L
.

3
8
,

N
O
.

2

º

2
0
0
5
P
e
c
e
n
l

A
d
v
a
n
c
e
s

i
n

l
h
e

C
h
e
m
i
s
l
r
y

o
l

L
i
l
h
i
u
m

A
m
i
n
o
b
o
r
o
h
y
d
r
i
d
e
s
group. This leads to an aldehyde, which is reduced Iurther to the
primary alcohol. In the case oI sterically more demanding LABs,
an imine is Iormed as an intermediate, which is then reduced to
the aminoalkane. For example, 1-pyrrolidinooctanamide can be
reduced either to 1-octanol (71°) with LiBH
3
(1-pyrrolidino) or 1-
pyrrolidinooctane (95°) with the sterically bulky LiBH
3
N(i-Pr)
2
.
1c

Based on these observations, it was thought that lactams might
behave similarly and lead to the corresponding cyclic amines
or ring-opened amino alcohols. UnIortunately, only 1-phenyl-
2-pyrrolidinone gave any ring-opened product with either
LiBH
3
NMe
2
or LiBH
3
N(i-Pr)
2
(eq 2).
3
3. Reduction o! Primary AIkyI 5uI!onates to
Hydrocarbons
Primary alkyl sulIonates undergo Iacile reduction to the
corresponding hydrocarbons with sterically hindered LABs
(eq 3).
4
UnIortunately, a sterically hindered LAB reagent will
not reduce secondary alkyl sulIonates, which are recovered
unchanged even aIter prolonged exposure at reIlux temperature.
For example, cyclohexyl methanesulIonate was completely
recovered aIter treatment with 2.5 equivalents oI LiBH
3
N(i-Pr)
2

in THF at 65 °C Ior 5 days.
4
4. Conversion o! Primary AIkyI MethanesuI!onates
to Amines
In contrast to the result shown in equation 3, when primary alkyl
methanesulIonates were treated with sterically unhindered LAB
reagents at 0 °C or 25 °C, no reduction products were Iormed.
Instead, the corresponding tertiary amines were observed by
GC analysis. Unexpectedly, under the reaction conditions,
LABs behave exclusively as amine-transIer agents. For example,
when treated with a variety oI LAB reagents, 3-phenylpropyl
methanesulIonate provides tertiary amines in excellent yields
aIter an acidic methanolic workup (eq 4).
4
The reduction oI alkyl methanesulIonates with unhindered
LAB reagents is possible, however, in the presence oI Et
3
B. Under
these reaction conditions, LiBHEt
3
is generated in situ. Using 1.5
equiv oI LiBH
3
NMe
2
and 20 mol ° oI Et
3
B, the reduction oI both
primary and secondary alkyl mesylates is accomplished in very
high yields (eq 5).
4

5. Tandem Amination-Reduction Reactions
The reaction oI LABs with benzonitriles containing ring halogens
has provided some very interesting results. Treatment oI 2-
chlorobenzonitrile with LiBH
3
NMe
2
in reIluxing THF aIIorded
a 90° isolated yield oI a 70:30 mixture oI 2-(dimethylamino)-
benzylamine (the product oI nucleophilic aromatic substitution
oI the chlorine by the dimethylamino groupanother example
oI nitrogen transIerIollowed by reduction oI the cyano
group) and 2-chlorobenzylamine (Scheme 2).
5,6
Reaction oI 2-
chlorobenzonitrile with lithium pyrrolidinoborohydride under
similar conditions gave analogous results: a 70:30 mixture oI 2-
(pyrrolidino)benzylamine and 2-chlorobenzylamine. Treatment
oI 2-chlorobenzonitrile with pyrrolidine under similar conditions
gave only recovered starting material.
The tandem aminationreduction was Iurther studied with other
halogenated benzonitriles. Reaction oI 2-bromobenzonitrile with
lithium dimethylaminoborohydride gave 2-bromobenzylamine as
the maior product and the tandem aminationreduction product as
the minor product (Scheme 3).
6
This is not surprising in light oI
the known order oI reactivity oI aryl halides in S
N
Ar substitution
reactions, with the bromo being the least reactive and the Iluoro
the most reactive.
eq 1
eq 2
eq 3
eq 4
eq 5
5cheme 1. Summary o! Ihe ReducIioh ReacIiohs o! LA8s.
63
V
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.

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,

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.

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2
0
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5
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b
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|
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Treatment oI 2- and 4-Iluorobenzonitriles with lithium
pyrrolidinoborohydride in THF at reIlux aIIorded 84°
and 89° yields, respectively, oI the corresponding
pyrrolidinobenzylaminesthe tandem aminationreduction
products (Scheme 4).
6
The reaction oI 2-Iluorobenzonitrile with
various lithium N,N-dialkylaminoborohydrides is Iairly general
and gives the corresponding 2-(N,N-dialkylamino)benzylamines in
very good yields (eq 6).
6
Thus, a wide variety oI amines, Irom the
very nucleophilic, such as pyrrolidine, to the less nucleophilic, such
as morpholine, undergo N-substitution with 2-Iluorobenzonitriles
via LAB reagents.
5a,6

6. 5ynthesis o! 2-(DiaIkyIamino)pyridines
Aminopyridines are attractive synthetic targets, since many
are biologically active molecules. For example, several
aminopyridine-based pharmaceuticals are used to treat a range oI
disorders.
7ae
In addition, and because oI their chelating properties,
aminopyridines are commonly used as ligands in inorganic and
organometallic chemistry.
7I,g
Aminopyridines substituted with
optically active groups could also serve as chiral auxiliaries or
chiral ligands in asymmetric reactions.
We have extended the amination capabilities oI LABs to 2-
Iluoropyridine. The direct amination oI 2-Iluoropyridine with
LABs was Iirst attempted to determine iI an amination reaction
analogous to that oI 2-Iluorobenzonitrile was indeed possible.
The same reaction conditions that had been optimized Ior the
amination oI 2-Iluorobenzonitrile were employed. Upon addition
oI 2-Iluoropyridine to a THF solution oI LiBH
3
NMe
2
, the colorless
solution turned deep red in color. Meisenheimer complexes, the
anionic intermediates Iormed during an S
N
Ar reaction, are known
to Iorm highly colored solutions. In Iact, a similar deep-red color
change in the S
N
Ar reactions oI LABs with 2-halobenzonitriles
had been observed. GratiIyingly, 2-(dimethylamino)pyridine was
isolated in 59° yield. AIter these initial Iindings, attempts were
made to optimize the reaction conditions. We discovered that
elevated reaction temperatures were unnecessary and only 1.1 equiv
oI LAB reagent was required Ior the desired transIormation.
When 2-Iluoropyridine was reacted at room temperature with
1.1 equiv oI lithium homopiperidinoborohydride in THF Ior
1 h, 2-(homopiperidino)pyridine was isolated in 97° yield
aIter employing the modiIied workup procedure. The products
oI the reaction oI various LAB reagents with 2-Iluoropyridine
are shown in equation 7.
8
The optically active LAB reagent
prepared Irom (S)-(¹)-2-methylpiperidine gave the lowest yield
(60°), presumably as a result oI increased steric requirements.
2-Chloropyridine reacted similarly with LiBH
3
NMe
2
(THF, 65 °C,
1 h) and led to 2-dimethylaminopyridine in 87° yield.
8

It is important to note that when 2-Iluoropyridine is heated
with a Iree amine such as homopiperidine at reIlux temperature,
the substrate remains intact even aIter an extended period oI time.
Other amines, speciIically, sterically hindered lithium amides such
as LDA, do not promote the amination oI 2-halopyridines: instead,
these reagents lead to ortho lithiation.
9
Our investigations oI the possible mechanism oI the reaction oI
2-Iluoropyridine with LABs led us to hypothesize that the pyridine
could be activated by coordination to boron during the reaction.
10

To test this hypothesis, we treated 2-Iluoropyridine with BH
3
·SMe
2

to Iorm a 2-Iluoropyridineborane complex. We then reacted the
complex with LiNPr
2
(Iormed Irom dipropylamine and n-BuLi) at
0 °C: 2-dipropylaminopyridine was isolated Irom this reaction in
50° yield (Scheme 5).
10

This unexpected result led us to investigate the importance oI
pre-activating 2-Iluoropyridine with BH
3
. When 2-Iluoropyridine
5cheme 2. 1ahdem AmihaIioh-ReducIioh
o! 2-ChlorobehzohiIrile.
5cheme 3. 1ahdem AmihaIioh-ReducIioh
o! 2- ahd 4-8romobehzohiIriles.
5cheme 4. 1ahdem AmihaIioh-ReducIioh
o! 2- ahd 4-FluorobehzohiIriles.
eq 6
64
V
O
L
.

3
8
,

N
O
.

2

º

2
0
0
5
P
e
c
e
n
l

A
d
v
a
n
c
e
s

i
n

l
h
e

C
h
e
m
i
s
l
r
y

o
l

L
i
l
h
i
u
m

A
m
i
n
o
b
o
r
o
h
y
d
r
i
d
e
s
was reacted with lithium pyrrolidide, in the absence oI BMS, we
were pleasantly surprised to Iind that 2-pyrrolidinopyridine was
obtained in 80° yield. To determine the scope oI this new amination
method, a series oI primary and secondary lithium amides were
reacted with 2-Iluoropyridine, which led to the corresponding 2-
aminopyridines in 1085° yields (eq 8).
10
Interestingly, treatment
oI 2-chloro- and 2-bromopyridines with lithium amides under the
same conditions led to the opening oI the pyridine ring (eq 9).
10
Clearly, the amination oI 2-halopyridines with LABs
operates under a diIIerent mechanism than the amination oI 2-
halopyridines with non-sterically hindered lithium amides. The
reaction oI 2-Iluoropyridine with both LABs and lithium amides
provides the same amination product. On the other hand, the
reaction oI 2-chloro- and 2-bromopyridines with LABs generates
an aminopyridine, while the use oI a lithium amide causes the
opening oI the pyridine ring.
7. TheoreticaI CaIcuIations on LAßs
Theoretical calculations oI the equilibrium geometries and
energies oI LABs, carried out by Pratt and co-workers, indicate that
LiBH
3
NMe
2
exists largely as a hydrogen-bridged dimer in both the
gas phase and as the bis(dimethyl ether) microsolvate (Figure 1).
11

More recently, this group utilized Density Functional Theory
(DFT) calculations to determine the eIIects oI ethereal solvents
on the aggregation state oI LiBH
3
NMe
2
. The calculations suggest
that the dimer might coexist with the monomer in tetrahydroIuran.
More hindered lithium dialkylaminoborohydrides exist primarily
as monomers in ethereal solutions.
12
The kinetics (pseudo-Iirst
order in 1-chlorodecane) oI the amination oI 1-chlorodecane with
LiBH
3
NMe
2
(THF, 25 °C) showed no detectable change in reaction
rate with time, suggesting that LiBH
3
NMe
2
exists primarily as a
monomer in THF, although the possibility oI monomerdimer
equilibration cannot be ruled out.
8. ConcIusions
Lithium aminoborohydrides are a new class oI powerIul yet
selective reducing agents that reproduce, in air, virtually all oI
the transIormations Ior which LiAlH
4
is now used. The reactivity
oI LABs is comparable to that oI both LiAlH
4
and Vitride
®
. LABs
are air-stable, nonpyrophoric, thermally stable, and liberate
hydrogen only slowly in protic solvents above pH 4. LABs,
whether solid or as THF solutions, retain their chemical activity
Ior at least 6 months when stored under nitrogen at 25 °C. LABs
can be synthesized Irom any primary or secondary amine, thus
allowing precise control oI the steric and electronic environments
oI these reagents.
The spectrum oI reactions oI lithium aminoborohydrides is
not limited to their reducing properties, since, in several cases
(e.g., reaction with halopyridines), LABs can also transIer their
amine moiety. Both hydride and amine can be transIerred in
tandem aminationreduction reactions oI halobenzonitriles.
In undergraduate teaching laboratories, transIormations that
would seldom be attempted because oI the need to use LiAlH
4
or
boranesuch as the reduction oI tertiary amides or estersmay
become routine experiments with the use oI LABs. For example,
Ior the past Iour years, students at the University oI CaliIornia,
Santa Cruz, who have taken the introductory organic chemistry
laboratory class, have employed 1 M THF solutions oI LABs
to reduce aliphatic, aromatic, and A,B-unsaturated esters to the
corresponding aliphatic, aromatic, and allylic alcohols, in air, in
7098° isolated yields without incident or diIIiculty. In academic
research laboratories, the short reaction time, ease oI generation
and handling, and simple workup procedure oI reductions with
eq 7
5cheme 5. AcIivaIioh o! 2-Fluoropyridihe wiIh H
3
8ºSMe
2
.
eq 8
eq 9
Figure 1. Hydrogeh-8ridged LA8 Dimer
(Cas Phase) ahd Mohomer (ih 1HF).
65
V
O
L
.

3
8
,

N
O
.

2

º

2
0
0
5
|
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b
o
v

|
a
:
u
m
a
n
:
|
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.

b
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n

5
|
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m
.

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d

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|
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|
|
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1
.

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a
|
:
|
|
LABs make these new reagents attractive alternatives to LiAlH
4

or LiAlHEt
3
(Super-Hydride
®
) reductions.
9. AcknovIedgements
ProIessor H.C. Brown had a long association with UC Santa Cruz.
In the nineties, he oIten visited UCSC, and the students, both in
our research group and undergraduates at UCSC, enioyed a great
deal his visits and their interaction with him. ProIessor Brown
gave his last public lecture (on General Asymmetric Syntheses
via Organoboranes) here at UCSC in May oI 2003 at the Bunnett
Lectures. It would be diIIicult to imagine modern organic
chemistry without the numerous and signiIicant contributions
Irom Brown`s laboratories, as attested to by a look at any current
organic chemistry iournal or textbook. Some oI us were very
Iortunate to have experienced a long association with ProIessor
Brown, and will dearly miss him. His legacy will be carried on
by his many Iormer students and organoborane chemists.
10. Re!erences and Notes
(f) Dedicated to ProIessor Herbert C. Brown, who passed away on
December 19, 2004.
(1) (a) Fisher, G. B.: Harrison, J.: Fuller, J. C.: Goralski, C. T.:
Singaram, B. Tetrahearon Lett. 1992, 33, 4533. (b) Fuller, J. C.:
Stangeland, E. L.: Goralski, C. T.: Singaram, B. Tetrahearon Lett.
1993, 34, 257. (c) Fisher, G. B.: Fuller, J. C.: Harrison, J.: Goralski,
C. T.: Singaram, B. Tetrahearon Lett. 1993, 34, 1091. (d) Fisher,
G. B.: Fuller, J. C.: Harrison, J.: Alvarez, S. G.: Burkhardt, E. R.:
Goralski, C. T.: Singaram, B. J. Org. Chem. 1994, 59, 6378. (e)
Singaram, B.: Fisher, G. B.: Fuller, J. C.: Harrison, J.: Goralski,
C. T. U.S. Patent 5,466,798, November 14, 1995.
(2) (a) Godioian, G.: Fisher, G. B.: Goralski, C. T.: Singaram,
B. In Reauctions in Organic Svnthesis: Abdel-Magid, A.
F., Ed.: ACS Symposium Series 641: American Chemical
Society: Washington, DC, 1996: pp 153166. (b) Goralski, C.
T.: Singaram, B.: Collins, C. J.: Cuzens, J. R.: Lanz, M. In
Organoboranes for Svntheses: Ramachandran, P. V., Brown,
H. C., Eds.: ACS Symposium Series 783: American Chemical
Society: Washington, DC, 2001: pp 1832.
(3) Flaniken, J. M.: Collins, C. J.: Lanz, M.: Singaram, B. Org. Lett.
1999, 1, 799.
(4) Thomas, S.: Huynh, T.: Enriquez-Rios, V.: Singaram, B. Org.
Lett. 2001, 3, 3915.
(5) (a) Thomas, S.: Collins, C. J.: Goralski, C. T.: Singaram, B. Chem.
Innov. 2000, 30 (August), 31. (b) The isolation oI 2-aminonitriles
at low temperatures was consistent with the nitrogen transIer
taking place beIore reduction oI the cyano group.
(6) Thomas, S.: Collins, C. J.: Cuzens, J. R.: Spiciarich, D.: Goralski,
C. T.: Singaram, B. J. Org. Chem. 2001, 66, 1999.
(7) (a) Schtive, S. R.: Petrie, M. D.: McDermott, M. P.: Tierney, D.
H.: Maso, D. H.: Goodman, A. D. Neurologv 1997, 48, 817. (b)
Sllin, L. C. Mea. Biol. 1981, 59, 11. (c) Davidson, M.: Zemishlany,
J. H.: Mohs, R. C. Biol. Psvchiatrv 1988, 23, 485. (d) Segal, J.
L.: Warner, A. L.: Brunnemann, S. R.: Bunten, S. C. Am. J.
Therapeutics 2002, 9, 29. (e) Cacchi, S.: Carangio, A.: Fabrizi, G.:
Moro, L.: Pace, M. Svnlett 1997, 1400. (I) Kempte, R.: Brenner,
S.: Arndt, P. Organometallics 1996, 15, 1071. (g) Fuhrmann, H.:
Brenner, S.: Arndt, P.: Kempe, R. Inorg. Chem. 1996, 35, 6742.
(8) Thomas, S.: Roberts, S.: Pasumansky, L.: Gamsey, S.: Singaram,
B. Org. Lett. 2003, 5, 3867.
(9) (a) Choppin, S.: Gros, P.: Fort, Y. Eur. J. Org. Chem. 2001, 603.
(b) Radinov, R.: Haimova, M.: Simova, E. Svnthesis 1986, 886.
(10) Pasumansky, L.: Hernandez, A. R.: Gamsey, S.: Goralski, C. T.:
Singaram, B. Tetrahearon Lett. 2004, 45, 6417.
D
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Lab No¦es, A|dr|ch|m|ca Ac|a). fo| subr|¦¦|ug ,ou| |dea, ,ou w||| |ece|.e a
coro||reu¦a|, /|d||c| oe||od|c ¦ab|e oos¦e| |Ca¦. No. Z54,320-9). l¦ we
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oe||od|c ¦ab|e rouse oad
|Ca¦. No. Z54,323-3). l¦ |s
!e¦ou
®
·coa¦ed, 8.5 × 11 |u.,
w|¦| a ¦u||·co|o| oe||od|c ¦ab|e
ou ¦|e ¦|ou¦. we |ese|.e ¦|e
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(11) Mogali, S.: Darville, K.: Pratt, L. M. J. Org. Chem. 2001, 66, 2368.
(12) Pratt, L. M.: Mogali, S.: Glinton, K. J. Org. Chem. 2003, 68, 6484.
Super-Hydride is a registered trademark oI Sigma-Aldrich Biotechnology,
L.P. Vitride is a registered trademark oI RutherIord Chemicals, LLC.
About the Authors
Lubov Pasumansky was born in St. Petersburg, Russia. She
received her Bachelor oI Science degree in chemistry Irom the
University oI CaliIornia, Santa Cruz, in 2001. She is currently
studying Ior her Ph.D. degree at the University oI CaliIornia,
Santa Cruz, under the supervision oI ProIessor B. Singaram. Her
doctoral research Iocuses on developing synthetic methodologies
that utilize lithium aminoborohydrides and lithium amides.
Bakthan Singaram was born in 1950 in Madanapali, India.
He received his Bachelor oI Science degree in chemistry in 1969
Irom the University oI Madras, India. He completed his master`s
(1971) and doctoral studies (1977) at the University oI Madras,
working with ProIessor James Verghese. He did his postdoctoral
research Iirst at Purdue University with ProIessor H. C. Brown and
later at the University College oI Swansea, Wales, with Andrew
Pelter. He returned to Purdue University in 1982 as assistant
research scientist to H. C. Brown. In 1987, he became associate
research scientist and, in 1989, ioined the Iaculty at the University
oI CaliIornia, Santa Cruz, as an assistant proIessor oI chemistry.
He was promoted to associate proIessor in 1995 and then Iull
proIessor in 1999. He is a recipient oI the Excellence in Teaching
Award Irom the University oI CaliIornia, Santa Cruz (1995). His
research interests include organoborane chemistry, asymmetric
catalysis, glucose detection with boronic acid receptors, and
materials chemistry.
Christian T. Goralski was born in 1942 in Cleveland,
Ohio. He received his Bachelor oI Science degree in chemistry
Irom Case Institute oI Technology in 1964. He then moved to
Purdue University and received his Ph.D. degree in organic
chemistry in 1969 under the direction oI ProIessor William E.
Truce. He ioined the Dow Chemical Company in November oI
1968. During the Iall oI 1985 and the spring oI 1986, he spent 6
months as an industrial postdoctoral scholar in the laboratory oI
ProIessor Herbert C. Brown at Purdue University investigating
the asymmetric hydroboration oI enamines. He retired Irom the
Dow Chemical Company in July 2004 aIter 30 years oI working
in the area oI organic process research Ior the manuIacture oI
pharmaceuticals. He is a member oI the editorial advisory board
oI Organic Process Research ana Development, and, in 2002,
received a Distinguished Alumnus Award Irom the School oI
Science at Purdue University.
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CH£MlCAL S¥NTH£SlS TlTL£S
Organic 5yntheses via ßoranes, VoIume 1
|. C. brown. A|dr|ch Chem|ca|. 1997. 23Joo.
|ardcover. This is a reprinl ol H. C. 8rown's
!975 lille conlaining a delailed discussion ol
organoboranes in organic synlhesis.
Z40,094-7 S29.95
Organic 5yntheses via ßoranes, VoIume 2
Recent DeveIopments
|. Za|d|ew|cz and |. C. brown. A|dr|ch Chem|ca|.
2001. J74oo. |ardcover. This book provides an
accounl ol recenl developmenls in organoborane
chemislry. Topics include hydroboralion wilh
borane and borane derivalives, organoborane
conversions lo lunclional groups, and carbon
carbon-bond lormalion via organoboranes.
Z40,095-5 S39.95
Organic 5yntheses via ßoranes, VoIume 3
5uzuki CoupIing
A. 5uzu|| and |. C. brown. A|dr|ch Chem|ca|.
200J. J14oo. |ardcover. ln lhis volume, various
aspecls ol lhe Suzuki coupling reaclion are
discussed such as preparalion ol organoboranes
lor Suzuki coupling and coupling wilh alkyl-,
alkenyl-, alkynyl-, and arylboranes.
Z51,430-6 S70.70
Dead Ends and Detours. Direct Ways to
5uccess!uI TotaI 5ynthesis
|. 5|erra. |. de |a 1orre. r. C. N|co|aou (|orewordì.
W||ev. 200¯. 290oo. 5o||cover. ln almosl all
publicalions, lhe valuable inlormalion provided
is almosl always based on successlul organic
reaclions. 8ul, il would be uselul lo have access
lo lhose synlheses lhal do nol work, since lhey
also provide imporlanl resulls ol greal imporlance
lor lurlher synlhesis. This book lills jusl such a
gap. Using major lolal synlheses, lhe aulhors
explain a variely ol problems and recommend
ways oul ol such dilemmas. Problems al lhe slarl
and end ol a synlhesis, dillicull and unexpecled
reaclivilies ol lunclional groups, problems due lo
sleric properlies and much more.
Z70,336-2 S79.95
CataIysts !or fine ChemicaI 5ynthesis,
VoIume 1, HydroIysis, Oxidation and Reduction
5. |ober|: and C. |o|qnan|. |d:.. W||ev. 2002.
224oo. |ardcover. ln lhis volume, lhe review
seclion conlains a reporl on lhe inlegralion ol
biolranslormalions inlo lhe calalysl porllolio.
The procedure seclion conlains a wide variely
ol synlhelic prolocols, such as epoxidalions
ol unsaluraled kelones and eslers, asymmelric
reduclions ol carbonoxygen double bonds,
asymmelric hydrogenalions ol carboncarbon
double bonds and olher lypes ol reaclion. The
lealured calalysls include a wide range ol dillerenl
malerials such as poly-D-leucine, D-lruclose-
based dioxiranes, oxaborolidine borane, some
imporlanl lilanium and rulhenium complexes
as well as baker's yeasl. lor each reaclion, lhere
is one or several delailed prolocols on how lo
prepare and employ lhe various calalysls.
Z54,160-5 S!49.95
Transition MetaIs !or Organic 5ynthesis.
ßuiIding ßIocks and fine ChemicaIs, 5econd
Edition, 2-VoIume 5et
|. be||er and C. bo|m. |d:.. W||ev. 2004.
1JJ4oo. |ardcover. Over 70 inlernalionally
renowned aulhors cover lhe vasl range ol
possible applicalions lor lransilion melals in
induslry as well as academia. This lwo-volume
work presenls lhe currenl slale ol research and
applicalions in lhis economically and scienlilically
imporlanl area ol organic synlhesis as well as in
lhe produclion ol line chemicals. Over !,000
illuslralions and lhe balanced presenlalion allow
readers lasl access lo lhe lhorough compilalion
ol applicalions.
Z70,345-1 S5!5.00
Reductions by the AIumino- and ßorohydrides
in Organic 5ynthesis, 5econd Edition
I. 5evden-|enne. |. C. brown (|orewordì. W||ev.
1997. 224oo. |ardcover. This updaled second
edilion is a guide lo lhe seleclion ol reducing
reagenls in organic synlhesis. ll is lhe only
relerence locusing exclusively on aluminohydrides
and borohydrides and lheir derivalives.
Z40,496-9 S94.95
5ide Reactions in Organic 5ynthesis.
A Guide to 5uccess!uI 5ynthesis Design
|. Z. |örwa|d. W||ev-vC|. 200¯. J39oo. 5o||cover.
Mosl synlheses in lhe chemical research laboralory
lail, and usually require several allempls belore
proceeding salislaclorily. Many lailures may,
however, be avoided by underslanding lhe slruclure
reaclivily relalionship ol organic compounds. This
lexlbook highlighls lhe compeling processes and
limilalions ol lhe mosl imporlanl reaclions used in
organic synlhesis. 8y allowing chemisls lo quickly
recognize polenlial problems, lhis book will help
improve lheir elliciency and success rale.
Z70,335-4 S!!0.00
DRUG DlSCOv£R¥ TlTL£
Contemporary Drug 5ynthesis
I.-I. ||. |. 5. Iohn:on. |. |. 5||:|ov|c. and b.
|. |o|h. W||ev. 2004. 221oo. |ardcover. This
book examines how leading researchers and
manulaclurers have inlegraled chemislry, biology,
pharmacokinelics, and a hosl ol olher disciplines
in lhe crealion and developmenl ol leading drugs.
This limely volume locuses on lhe processes lhal
resulled in high-prolile drugs. ll provides an in-
deplh inlroduclion lo each drug, lollowed by a
delailed accounl ol ils synlhesis, and organizes
lhe drugs inlo lourleen lherapeulic areas lor
clarily and ease ol use.
Z70,353-2 S89.95
SP£ClAL TOPlCS TlTL£
Candid 5cience. Conversations vith famous
Chemists
|. |arq|||a|. |moer|a| Co||eqe |re::. 2000. ¯16oo.
5o||cover. Thirly-six lamous chemisls, including
Linus Pauling and Herberl C. 8rown, lell aboul
lheir lives in science, lhe beginnings ol lheir
careers, lheir aspiralions, and lheir hardships
and lriumphs. NMP speclroscopy, compulalional
chemislry, lhe drama ol buckminslerlullerene, lhe
slory ol lhe Pill, lhe polilics ol almospheric chemislry
and resonance lheory, and lhe beginnings ol
molecular mechanics and modern slereochemislry
are examples ol lhe lopics discussed.
Z55,383-2 S34.00
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