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Synthetic Communications: An
International Journal for Rapid
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Formation of Specific Enolates

and Enamines from 3-
Heteracyclohexanones
a a b
Jerry A. Hirsch & Xiao Lan Wang
a
Department of Chemistry , Seton Hall University ,
South Orange, New Jersey, 07079
b
Visiting Scholar from Nankai University , Tianjin,
People's Republic of China , 1979-1981
Published online: 01 Apr 2009.

To cite this article: Jerry A. Hirsch & Xiao Lan Wang (1982) Formation of Specific
Enolates and Enamines from 3-Heteracyclohexanones, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 12:5,
333-337

To link to this article: http://dx.doi.org/10.1080/00397918209408006

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 SYNTHETIC COIIMUNICATIONS, 12(5), 333-337 (1982)

FORMATION OF SPECIFIC ENOLATES AND

ENAMINES FROM 3-HETERACYCLOHEXANONES
Downloaded by [Universitaets und Landesbibliothek] at 16:24 31 October 2013

*
Jerry A. Hirsch and Xiao Lan Wang'
Department of Chemistry, Seton Hall University
South Orange, New Jersey 07079

Regioselective formation of enolates (kinetic and thermody-

namic control) and of enamines have been studied using 3-oxacyclo-
hexanone (1)and
3-thiacyclohexanone (g),both prepared by methods
previously utilized. 1
Enamine formation from 1 using rnorpholine and from 2. u s i n g
2
pyrrol idine or morpholine produced that regioisomer w i t h the
double bond toward the heteroatom i n greater than 80%yield. In
conjunction w i t h 1i t e r a t u r e examples 3 of analogous nitrogen sys-
tems, the pattern clearly i s enamine regioselectivity ( o r possibly
regiospecifici ty) toward the heteroatom, presumably from herero-
atom stabilization o f the double-bond 4 i n a thermodynamic sense. 5
Under conditions of base-catalyzed thermodynamic control , 6 y 7
thiaketone 2 produced only t h a t s i l y l enol ether corresponding t o
*
To whom correspondence should b e addressed.
+V i s i t i n g
Scholar from Nankai University, T i a n j i n , People's
Republic of China, 1979-1981.

333
 334 HIRSCH AND WANG

double bond formation toward t h e heteroatom, para1l e l i n g t h e p r e f -

erences i n t h e n i t r o g e n cases.6 However, oxaketone 1 formed the

opposite regioisomer r e g i o s e l e c t i v e l y (89:11), i n agreement w i t h

t h e o n l y isomer found on acid-catalyzed formation o f enol acetates

under thermodynamic c o n t r o l .a Under conditions o f thermodynamic

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c o n t r o l , enol i z a t i o n toward t h e heteroatom i s t h e r e f o r e p r e f e r r e d

#
6
i n t h e s u l f u r and n i t r o g e n systems, b u t n o t i n t h e oxygen system.
I n t e r p r e t a t i o n i s hampered by evidence
7 t h a t enolate anion and

enol e t h e r e q u i l i b r a t i o n s are both f e a s i b l e under these conditions,

plus t h e aminoketones may i n v o l v e amnonium ketone o r a m n i u m

6
enolate species as w e l l .

Under c o n d i t i o n s o f k i n e t i c c o n t r o l ,6’7 thiaketone 2is con-

v e r t e d almost completely t o t h e same regioisomer as under thermo-

dynamic c o n t r o l , b u t approximately 2.5% of t h e o t h e r isomer

i s produced. Oxaketone 1a l s o favors t h e same s i l y l enol e t h e r

regioisomer as under thermodynamic c o n t r o l b y 75-88% (compared t o

8
Dickinson’s 76% f o r t h e enol acetates . Apparently under condi-

t i o n s of k i n e t i c c o n t r o l , t h e hydrogen alpha t o t h e heteroatpm i s

more a c i d i c than t h e hydrogen gamma t o t h e heteroatom i n t h e s u l -

fur system and i n t h e corresponding urethanes,6 b u t l e s s a c i d i c

6
i n t h e oxygen and N-alkyl systems. The enolate anion r e s u l t i n g

from a b s t r a c t i o n of t h e alpha hydrogen must be k i n e t i c a l l y desta-

b i l i z e d by heteroatom lone p a i r - enolate anion repulsions, 6,lO

b u t t h i s i n t e r a c t i o n dominates” heteroatom p o l a r e f f e c t s o n l y

when t h e heteroatom lone p a i r i s 2p ( o r a h y b r i d d e r i v e d there-

from) and i s e x t e n s i v e l y l o c a l i z e d on t h e heteroatom.

 3-HETEMCYCLOHEXANONES 335

The synthetic imp1 ications of our r e s u l t s coupled with Garst's 6

are s i g n i f i ca n t . Regioselectivity may be a function of the hetero-
atom present w i t h further control possible by proper choice of
heteroatom substitution, and reagents. Enamines enolates gener-
ated under kinetic control, and enolates generated under thermody-
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namic control each have a role t o play i n this respect.

Experimental Section
Enamines. Standard procedure^^'^ were ut ilized. The pyrrol idine
enamine of 3-thiacyclohexanone was formed in 83.6% yield, b.p.
2
88-90" (0.08 mm) ( l i t . 2 100" (0.lOmm)); spectra as reported.
The morpholine enamine of this ketone was formed in 81%y i e l d ,
b.p. 110" (0.8 mn); pmr (CDC13) 6 5.02 ( s , lH), 3.77 ( m y 4H),

2.80 (m, 6H), 2.2 (m, 4H). The morpholine enarnine of 3-oxacyclo-
hexanone e x h i b i t e d b.p. 72" (0.1 mm); pmr (CDC13) 6 6.03 ( s , lH),
3.72 (m, 6H), 2.65 (m, 4H), 1.73-2.10 (my 4H).
Silyl en01 ethers. Kinetic control. Using the method o f Garst, 6
3-thiacyclohexanone was converted t o the s i l y l enol ethers. Pre-
parative t l c on s i l i c a gel (25:3 methylene chloride n-hexane)
permitted separation of the major isomer (see below and t h e k n o r
isomer: it- (neat) 3020 and 1660 cm-', pmr (CDC13) 6 4.12 (broad,
lH), 2.67 (s, 2H), 2.17-2.57 (my 4H), 0.13 ( s , 9h). Glc (10%
Carbowax 20M and 20% SE-30 columns) and pmr integration showed
2.9%, 2.2%, 2.8%, 2.8%, 2.3%, 2.5%, and 2.0% o f the minor isomer
i n t h e crude enol e the r mixture.
6
When 3-oxacyclohexanone was subjected t o the Garst procedure
followed by f l a sh chromatography using benzene, the two isomers
were obtained as pure materials:
 336 HIRSCH AND WANG

major isomer: i r ( n e a t ) 3040 and 1665 cm"; pmr (CDC13)

6 4.95 (broad t, lH), 3.82-4.05 ( m y 2H), 3.58-3.82
( t , 2H), 1.92-2.35 ( m , 2 H ) , 0.22 ( s , 9H).
minor isomer: i r ( n e a t ) 3020 and 1620 cm"; pmr (CDC13)
6 6.28 ( s , lH), 3.45-3.98 ( m y 2H), 1.75-2.28 (m, 4H),
Downloaded by [Universitaets und Landesbibliothek] at 16:24 31 October 2013

0.18 ( s , 9H).
The crude enol e t h e r mixture was not separable by g l c , b u t pmr
integration showed 75%, 83%, and 88%of the major isomer.
Thermodynamic control. Using a modification of t h e method of
House,7 3-thiacyclohexanone was converted t o enol ether i n 2 h r
a t 65-70'. Analyses indicated only one s i l y l enol e t h e r . Frac-
tional d i s t i l l a t i o n produced pure material , b.p. 62-64" (1.2 mn),
i r ( n e a t ) 3040 and 1620 cm"; pmr (CDC13) 6 5.22 ( s , l H ) , 2.53-
2.83 (my 2H), 2.12 (my 4H), 0.23 (s, 9H).
Treatment of 3-oxacyclohexanone by the same procedure gave
89% o f one isomer corresponding t o the mamor isomer from the k i -
n e t i c control runs and l l %of t h e minor s i l y l enol ether.
References
J . A. Hirsch and A A. Jarmas, J . Org. Chem., 43, 4106 (1978);
George Zweifel and Joseph Plamndon, J. Org. Chem. , 35, 898
(1970).
J. E. Young and L. J . Heitz, J . Org. Chem., 38, 1562 (1973).
S. Danishefsky and R. Cavanaugh, J. Org. Chem., 33, 2959 (1968);
J. Masamune, H. Hayashi, M. Takasugi, and S . Fukuoka, ibid.,
37, 2343 (1972); P. Krogsgaard-Larsen and H. Hjeds, Acta Chem.
c

Scand., f
E
iJ
, 884 (1976).
 3-HETERACYCLOHEXANONES 337

J . Hine and N. W. Flachskam, J. Am. Chem. SOC., 95, 1179 (1973);

'
J . Hine and S.-M. Linden, J. Org. Chem., 46, 1635 (1981); J.

Hine, S.-M. Linden, A. Wang, and V. Thiagarajan, i b i d . , 45,

2821 (1980); J . Hine, " S t r u c t u r a l E f f e c t s on E q u i l i b r i a i n

Organic Chemistry," Wiley, N. Y., 1975.

Downloaded by [Universitaets und Landesbibliothek] at 16:24 31 October 2013

S. J. Martinez and J. A. Joule, Tetrahedron, 34, 3027 (1978);

P. Beeken and F. W. Fowler, J . Org. Chem., 45, 1336 (1980).

M. E. Garst, J. N. B o n f i g l i o , D. A. Grudoski, and J. Marks, J.

Org. Chem., 45, 2307 (1980), Tetrahedron Lett., 2671 (1978).

H. 0. House, L. J . Czubz; M. Gall, and H. D. Olmstead, J. Org.

Chem. , 3,2324 (1969).

C. M. Dickinson, Diss. Abstr. E,6164 (1976); D i s s e r t a t i o n ,

Emory U n i v e r s i t y , 1975, P a r t Two.

J. Hine and P. D. Dalsin, J . Am. Chem. SOC., 94, 6998 (1972).

loF. G. Bordwell e t a l , J. Org. Chem., 42, 326 (1977), 41, 1883,

1885 (1976); N. D. E p i o t i s , R. L. Yates, F. Bernardi, and S.

Wolfe, J. Am. Chem. SOC., 98, 5435 (1976); J.-M. Lehn and G.

Wipff, ibid., 98, 7498 (1976); A. S t r e i t w i e s e r and J. E. W i l -

liams, i b i d . , 97, 191 (1975).