Note

Cite This: J. Org. Chem. 2019, 84, 4429−4434 pubs.acs.org/joc

Asymmetric Synthesis of γ‑Hydroxy Pinacolboronates through

Copper-Catalyzed Enantioselective Hydroboration of α,β-
Unsaturated Aldehydes
Won Jun Jang,† Seung Min Song,† Yeji Park, and Jaesook Yun*
Department of Chemistry, Sungkyunkwan University, Suwon 16419, Korea
*
S Supporting Information
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ABSTRACT: We report a copper-catalyzed enantioselective

hydroboration of α,β-unsaturated aldehydes with pinacolbor-
ane. α,β-Unsaturated aldehydes were converted to the
corresponding γ-pinacolboronate alcohols in good yields and
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enantioselectivities through consecutive hydroboration of the

CO and CC bonds. This process provides simple access
to the hydroborated product of allylic alcohols, and the
resulting γ-pinacolboronate alcohols could be utilized in
various transformations.

T he hydroboration of alkenes is one of the fundamental

methods to produce organoboron compounds, which are
recognized as versatile synthetic intermediates in organic
Scheme 1. Asymmetric Hydroboration Reactions of Allylic
Alcohol Derivatives

synthesis.1 In recent decades, there have been significant

advances in the transition-metal-catalyzed hydroboration field,
allowing highly regio- and enantioselective syntheses of chiral
alkylboron compounds.2 Moreover, a range of stereospecific
transformations of carbon−boron bonds to other function-
alities have increased the synthetic utility of organoboranes,
which has further encouraged investigations on the efficient
synthesis of chiral organoboron compounds.3
Controlling regioselectivity and enantioselectivity in the
asymmetric hydroboration of terminal olefins has been an
important issue, as most transition-metal catalytic systems
produce anti-Markovnikov addition products, linear products
with no chiral center, or a mixture of products.4 While
regioselective hydroboration of internal alkenes is more
challenging than that of terminal alkenes, our group previously
disclosed that copper(I)−bisphosphine catalysts could hydro-
borate vinyl arenes and disubstituted internal alkenes with high
regio- and enantioselectivities with pinacolborane as the
hydroborating reagent.5 In particular, copper(I) chloride and
DTBM-Segphos (L*) as the chiral ligand was the most
effective catalytic combination for the asymmetric hydro-
boration of both terminal and internal alkenes, producing
secondary alkylboronates with high enantioselectivity.5b,c
Studies on the asymmetric hydroboration of internal allylic chiral copper(I)−bisphosphine complexes, we decided to
alcohols are rare, and only a few examples of hydroborations of investigate this catalytic system in the asymmetric hydro-
protected terminal allylic alcohols have been reported in Rh- boration of internal allylic alcohols. With the copper-(R)-
catalyzed directed hydroborations6 and hydroboration of an
allylic ester with a copper catalyst5b (Scheme 1, A). Based on Received: November 29, 2018
our copper-catalyzed enantioselective hydroboration with Published: March 14, 2019

© 2019 American Chemical Society 4429 DOI: 10.1021/acs.joc.8b03045

J. Org. Chem. 2019, 84, 4429−4434
The Journal of Organic Chemistry Note

Scheme 2. Copper-Catalyzed Enantioselective Hydroborationa

a
General reaction conditions: 1 (0.5 mmol), pinacolborane (1.25 mmol), CuCl (0.025 mmol), ligand L* ((R)-DTBM-Segphos) (0.0275 mmol),
NaOt-Bu (0.05 mmol) in toluene (1 mL); see the Experimental Section for details. bIsolated yield. cDetermined by chiral HPLC analysis of the
corresponding diol 3.

DTBM-Segphos catalyst, however, hydroboration reaction of and 2j) were not very stable on SiO2, and thus, the
cinnamyl alcohol failed to give the desired product with no corresponding diols were obtained after oxidation. This
conversion (Scheme 1, B). We thought this problem could be protocol was not suitable for α,β-unsaturated aldehydes with
circumvented by using α,β-unsaturated aldehydes, hoping that β-alkyl substituents either, as the reaction produced fully
1,2-hydroboration of the aldehyde carbonyl would occur faster reduced, nonborylated alcohol products.8
than 1,4-hydroboration. Herein, we describe a copper- The hydroboration protocol was suitable for large-scale
catalyzed enantioselective hydroboration of α,β-unsaturated
synthesis (Scheme 3a). A 1.0 mol % loading of copper catalyst
aldehydes with pinacolborane to produce γ-pinacolboronate
alcohols. was sufficient to perform the hydroboration reaction on a 3.0
We started our investigation by examining the hydro-
boration of cinnamaldehyde 1a with copper catalyst (Scheme Scheme 3. Gram-Scale Synthesis and Transformation of
2). The reaction proceeded smoothly to afford target product Chiral Boron Products
2a in good yield and good enantioselectivity in toluene at 60
°C.7 Then, we investigated the substrate scope of cinnamalde-
hyde derivatives. Most of the desired products were obtained
in good yields and good enantioselectivities. A naphthyl moiety
(2b) was accommodated with no problem. Substrates with an
electron-donating or electron-withdrawing substituent at the
para position afforded the desired products (2c and 2d) in
good yields and enantioselectivities. The hydroboration
reaction was amenable to enal substrates with a methyl or
halogen substituent at the ortho- or meta-position of the aryl
group (1e−1h). Heteroaryl compounds (1i and 1j) such as 2-
benzofuranyl and 2-thienyl reacted with good conversion to
the desired products, but with slightly decreased enantiose-
lectivities. However, γ-hydroxy pinacolboronate products with
ortho-substitution (2g and 2h) or heteroaryl substituent (2i
4430 DOI: 10.1021/acs.joc.8b03045
J. Org. Chem. 2019, 84, 4429−4434
The Journal of Organic Chemistry
mmol scale of 1a. Despite the reduced amounts of catalyst and
ligand, 2a was produced in 82% yield and 90% ee. Next, the
chiral boronates (2a) were stereospecifically converted to
compounds containing a new C−C bond (Scheme 3b). Suzuki
coupling9 of 2a with 4-bromotoluene stereospecifically
produced the arylated product 410 in the presence of a
palladium catalyst. Both reactions occurred in high yields and
with complete conservation of the enantiomeric excess of the
original hydroborated products.
To investigate the mechanism of the hydroboration, an
NMR study was carried out with 1.1 equiv of pinacolborane to
detect a reaction intermediate (Scheme 4). The 1,2-hydro-
Scheme 4. NMR Study of Chemoselective Hydroboration of
Cinnamaldehyde
boration of the aldehyde carbonyl occurred faster than
conjugate addition, resulting in the formation of II, which
was chemically compatible to the yield of 2a by reaction with
HBpin.
A proposed catalytic cycle for the hydroboration of enals is
shown in Scheme 5. The active catalyst L*Cu−H reacts with
Scheme 5. Proposed Catalytic Cycle
the aldehyde to form the copper alkoxide I, which
subsequently reacts with HBpin to generate II and the active
L*Cu−H catalyst. Further hydroboration of intermediate II
with the catalyst forms an alkylcopper intermediate III, which
reacts with HBpin to form the final borylated product.
In summary, we have developed a copper-catalyzed
enantioselective hydroboration of α,β-unsaturated aldehydes
with pinacolborane. The DTBM-Segphos−copper catalyst was
4431
Note
effective in this transformation, furnishing useful chiral
hydroxyboronates with high enantioselectivities via consecutive
hydroboration of CO and CC bonds. Moreover, the
protocol could be easily scaled up to gram scale, and
stereospecific transformations of the resulting hydroxyboro-
nates to various compounds demonstrate their synthetic utility.
■
EXPERIMENTAL SECTION
General Methods. All reactions were carried out under a nitrogen
atmosphere using oven-dried glassware. CuCl, NaOt-Bu, pinacolbor-
ane, and other commercial reagents were purchased from Aldrich and
were used as received. (R)-DTBM-Segphos was purchased from TCI.
Unsaturated aldehydes 1b−1j were prepared following literature
procedures.11 All liquid aldehydes were distilled from calcium hydride,
and solid aldehydes were purified by recrystallization. Deactivated
silica gel was prepared by stirring a slurry of the silica gel in a 5 mol %
NaOAc aqueous solution for 30 min. Toluene was purified using the
PureSolv solvent purification system, from Innovative Technology,
Inc. All 1H NMR spectra were obtained on Bruker at 500 systems and
reported in parts per million (ppm) downfield from tetramethylsilane.
13
C NMR spectra were reported in ppm referenced to deuteriochloro-
form (77.16 ppm). 11B NMR spetra were obtained on Bruker at 400
systems at Kyonggi University (Suwon, Korea). High-performance
liquid chromatography (HPLC) was performed using Younglin Acme
9100 series. Infrared spectra (IR) were obtained on Nicolet 205 FT-
IR and were recorded in cm−1. High-resolution mass spectra (HRMS)
were obtained by the electrospray ionization (ESI) method using an
ion trap mass analyzer at Sogang Center for Research Facilities of
Sogang University (Seoul, Korea) and reported in the form of m/z
(intensity relative to peak = 100).
General Procedure for the Copper-Catalyzed Enantioselec-
tive Hydroboration of α,β-Unsaturated Aldehydes. A mixture
of CuCl (5 mol %, 0.025 mmol), (R)-DTBM-Segphos (5.5 mol %,
0.0275 mmol), and NaOt-Bu (10 mol %, 0.05 mmol) in toluene (0.5
mL) was stirred for 5 min in a Schlenk tube under an atmosphere of
nitrogen. Pinacolborane (2.5 equiv, 1.25 mmol) was added to the
reaction mixture, and stirring was continued for another 15 min at
room temperature. Substrate 1 (1 equiv, 0.5 mmol) dissolved in
toluene (0.5 mL) was added to the reaction mixture. The reaction
mixture was stirred at 60 °C and monitored by TLC. Upon
completion of the reaction, the reaction mixture was diluted with
ethyl acetate (10 mL) and water (10 mL). The aqueous layer was
extracted with ethyl acetate, and the combined organic layers were
dried over Na2SO4 and concentrated in vacuo. The product was
purified by deactivated silica gel chromatography. Rapid silica gel
chromatography (5 min) is imperative for reproducible results
because the γ-pinacolboronate alcohol decomposes readily on silica
gel.
For determination of enantiomeric excess (ee), the γ-pinacolbor-
onate alcohol was transformed to the corresponding diol by the
following procedure: To a solution of γ-pinacolboronate alcohol (1
equiv) in THF:H2O (2 mL, 1:1 (v/v)) was added sodium perborate
(3 equiv). The reaction mixture was stirred for 6 h at room
temperature. The reaction was quenched with water and extracted
with ethyl acetate. The product was purified by silica gel
chromatography.
General Procedure for the Gram-Scale Synthesis of γ-
Hydroxy Pinacolboronates. A mixture of CuCl (1 mol %, 0.03
mmol), (R)-DTBM-Segphos (1.1 mol %, 0.033 mmol), and NaOt-Bu
(2 mol %, 0.06 mmol) in toluene (0.5 mL) was stirred for 5 min in a
Schlenk tube under an atmosphere of nitrogen. Pinacolborane (2.5
equiv, 7.5 mmol) was added to the reaction mixture, and stirring was
continued for another 15 min at room temperature. Substrate 1 (1
equiv, 3 mmol) dissolved in toluene (0.5 mL) was added to the
reaction mixture. The reaction mixture was stirred at 60 °C and
monitored by TLC. Upon completion of the reaction, the reaction
mixture was diluted with ethyl acetate (10 mL) and water (10 mL).
The aqueous layer was extracted with ethyl acetate, and the combined
organic layers were dried over Na2SO4 and concentrated in vacuo. The
DOI: 10.1021/acs.joc.8b03045
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The Journal of Organic Chemistry
product was purified by deactivated silica gel chromatography. Rapid
silica gel chromatography (5 min) is imperative for reproducible
results because the γ-pinacolboronate alcohol decomposes readily on
silica gel.
(S)-3-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
propan-1-ol (2a). Following the general procedure, 2a was obtained
in 84% yield (110.3 mg, 0.42 mmol, colorless oil). Rf = 0.4 (EtOAc/
hexane = 1/1). 1H NMR (500 MHz, CDCl3) δ 7.28−7.21 (m, 4H),
7.16−7.13 (m, 1H), 3.71−3.64 (m, 1H), 3.63−3.55 (m, 1H), 2.44 (t,
J = 7.5 Hz, 1H), 2.16−2.09 (m, 1H), 1.95−1.89 (m, 1H), 1.51 (brs,
1H), 1.21 (s, 6H), 1.19 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ
142.7, 128.41, 128.40, 125.4, 83.5, 62.5, 35.6, 24.61, 24.58. The
carbon bonded to boron was not detected due to quadrupolar
relaxation. 11B{1H} NMR (128 MHz, CDCl3) δ 33.9. IR (neat) 3437,
2977, 1458, 1382, 1324, 1144 cm−1. HRMS (ESI-Ion Trap) m/z [M
+ H]+ calcd for C15H24BO3 263.1819, found 263.1820. 90% ee was
measured by chiral HPLC on an AD-H column with the
corresponding diol obtained after oxidation (i-PrOH:hexanes =
5:95, 0.5 mL/min); tR = 29.70 min (major), tR = 27.97 min (minor).
(S)-3-(Naphthalen-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)propan-1-ol (2b). Following the general procedure, 2b was
obtained in 78% yield (121.6 mg, 0.39 mmol, colorless oil). Rf = 0.4
(EtOAc/hexane = 1/1). 1H NMR (500 MHz, CDCl3) δ 7.79−7.74
(m, 3H), 7.66 (s, 1H), 7.45−7.38 (m, 3H), 3.74−3.69 (m, 1H),
3.66−3.60 (m, 1H), 2.63 (t, J = 7.5 Hz, 1H), 2.28−2.19 (m, 1H),
2.05−1.99 (m, 1H), 1.56 (brs, 1H), 1.21 (s, 6H), 1.19 (s, 6H).
13
C{1H} NMR (125 MHz, CDCl3) δ 140.3, 133.8, 131.8, 127.9,
127.6, 127.5, 127.4, 126.3, 125.8, 125.0, 83.6, 62.5, 35.4, 24.62, 24.60.
The carbon bonded to boron was not detected due to quadrupolar
relaxation. IR (neat) 3474, 3052, 2970, 1457, 1390, 1314, 1147 cm−1.
HRMS (ESI-Ion Trap) m/z [M + H]+ calcd for C19H26BO3 313.1975,
found 313.1977. 90% ee was measured by chiral HPLC on an AS-H
column with the corresponding diol obtained after oxidation (i-
PrOH:hexanes = 10:90, 0.5 mL/min); tR = 24.60 min (major), tR =
27.20 min (minor).
(S)-3-(4-Methoxyphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)propan-1-ol (2c). Following the general procedure, 2c was
obtained in 83% yield (121.0 mg, 0.41 mmol, colorless oil). Rf = 0.4
(EtOAc/hexane = 1/1). 1H NMR (500 MHz, CDCl3) δ 7.14−7.12
(m, 2H), 6.82−6.80 (m, 2H), 3.78 (s, 3H), 3.69−3.63 (m, 1H),
3.61−3.55 (m, 1H), 2.38 (t, J = 7.5 Hz, 1H), 2.11−2.04 (m, 1H),
1.91−1.85 (m, 1H), 1.50 (brs, 1H), 1.21 (s, 6H), 1.19 (s, 6H).
13
C{1H} NMR (125 MHz, CDCl3) δ 157.5, 134.6, 129.3, 113.9, 83.5,
62.4, 55.2, 35.9, 24.63, 24.59. The carbon bonded to boron was not
detected due to quadrupolar relaxation. IR (neat) 3401, 2978, 1608,
1511, 1447, 1380, 1324, 1216, 1141 cm−1. HRMS (ESI-Ion Trap) m/
z [M + H]+ calcd for C16H26BO4 293.1924, found 293.1926. 91% ee
was measured by chiral HPLC on an AD-H column with the
corresponding diol obtained after oxidation (i-PrOH:hexanes = 5:95,
0.5 mL/min); tR = 43.42 min (major), tR = 41.52 min (minor).
(S)-3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(4-
(trifluoromethyl)phenyl)propan-1-ol (2d). Following the general
procedure, 2d was obtained in 82% yield (140.3 mg, 0.43 mmol,
colorless oil). Rf = 0.4 (EtOAc/hexane = 1/1). 1H NMR (500 MHz,
CDCl3) δ 7.52−7.50 (m, 2H), 7.34−7.32 (m, 2H), 3.70−3.65 (m,
1H), 3.60−3.55 (m, 1H), 2.53 (t, J = 7.5 Hz, 1H), 2.19−2.11 (m,
1H), 1.94−1.88 (m, 1H), 1.54 (brs, 1H), 1.20 (s, 6H), 1.19 (s, 6H).
13
C{1H} NMR (125 MHz, CDCl3) δ 147.2, 128.6, 127.7 (q, J = 30
Hz), 125.3 (q, J = 3.8 Hz), 124.5 (q, J = 270 Hz), 83.8, 62.1, 35.3,
24.60, 24.57. The carbon bonded to boron was not detected due to
quadrupolar relaxation. IR (neat) 3444, 2958, 1445, 1381, 1325, 1124,
1015 cm−1. HRMS (ESI-Ion Trap) m/z [M + H]+ calcd for
C16H23BF3O3 331.1692, found 331.1690. 91% ee was measured by
chiral HPLC on an OD-H column with the corresponding diol
obtained after oxidation (i-PrOH:hexanes = 10:90, 0.5 mL/min); tR =
13.85 min (major), tR = 6.45 min (minor).
(S)-3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(m-tolyl)-
propan-1-ol (2e). Following the general procedure, 2e was obtained
in 80% yield (110.7 mg, 0.40 mmol, colorless oil). Rf = 0.4 (EtOAc/
hexane = 1/1). 1H NMR (500 MHz, CDCl3) δ 7.16−7.14 (m, 1H),
4432
Note
7.03−7.01 (m, 2H), 6.97−6.95 (m, 1H), 3.71−3.65 (m, 1H), 3.60−
3.54 (m, 1H), 2.40 (t, J = 7.5 Hz, 1H), 2.31 (s, 3H), 2.15−2.07 (m,
1H), 1.94−1.88 (m, 1H), 1.54 (brs, 1H), 1.21 (s, 6H), 1.20 (s, 6H).
13
C{1H} NMR (125 MHz, CDCl3) δ 142.6, 137.9, 129.3, 128.3,
126.2, 125.4, 83.5, 62.5, 35.7, 24.6, 21.5. The carbon bonded to boron
was not detected due to quadrupolar relaxation. IR (neat) 3347, 2968,
1467, 1371, 1311, 1134, 1008 cm−1. HRMS (ESI-Ion Trap) m/z [M
+ H]+ calcd for C16H26BO3 277.1975, found 277.1976. 91% ee was
measured by chiral HPLC on an AD-H column with the
corresponding diol obtained after oxidation (i-PrOH:hexanes =
5:95, 0.5 mL/min); tR = 30.01 min (major), tR = 28.29 min (minor).
(S)-3-(3-Fluorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)propan-1-ol (2f). Following the general procedure, 2f was
obtained in 81% yield (113.6 mg, 0.41 mmol, colorless oil). Rf = 0.4
(EtOAc/hexane = 1/1). 1H NMR (500 MHz, CDCl3) δ 7.23−7.19
(m, 1H), 6.99−6.93 (m, 2H), 6.85−6.82 (m, 1H), 3.71−3.65 (m,
1H), 3.60−3.55 (m, 1H), 2.46 (t, J = 7.5 Hz, 1H), 2.15−2.08 (m,
1H), 1.93−1.87 (m, 1H), 1.53 (s, 1H), 1.21 (s, 6H), 1.19 (s, 6H).
13
C{1H} NMR (125 MHz, CDCl3) δ 163.0 (d, J = 244 Hz), 145.4 (d,
J = 6.3 Hz), 129.7 (d, J = 8.8 Hz), 124.1 (d, J = 2.5 Hz), 115.1 (d, J =
21.3 Hz), 112.3 (d, J = 21.3 Hz), 83.7, 62.2, 35.4, 24.59, 24.56. The
carbon bonded to boron was not detected due to quadrupolar
relaxation. IR (neat) 3460, 2965, 1455, 1383, 1321, 1118 cm−1.
HRMS (ESI-Ion Trap) m/z [M + H]+ calcd for C15H23BFO3
281.1724, found 281.1722. 88% ee was measured by chiral HPLC
on an AS-H column with the corresponding diol obtained after
oxidation (i-PrOH:hexanes = 10:90, 0.5 mL/min); tR = 16.33 min
(major), tR = 18.92 min (minor).
(S)-1-(2-Chlorophenyl)propane-1,3-diol (3g). Following the gen-
eral procedure, 3g was obtained in 74% yield (69.3 mg, 0.37 mmol,
colorless oil). The characterization data for 3g were concordant with
that previously reported in the literature.12a Rf = 0.2 (EtOAc/hexane
= 1/1). 1H NMR (500 MHz, CDCl3) δ 7.65−7.63 (m, 1H), 7.33−
7.30 (m, 2H), 7.23−7.20 (m, 1H), 5.38−3.36 (m, 1H), 3.96−3.89
(m, 2H), 3.09 (brs, 1H), 2.28 (brs, 1H), 2.08−2.04 (m, 1H), 1.97−
1.89 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 141.5, 131.4,
129.4, 128.5, 127.2, 127.1, 71.2, 61.8, 38.5. 87% ee was measured by
chiral HPLC on an OJ-H column (i-PrOH:hexanes = 5:95, 0.5 mL/
min); tR = 47.78 min (major), tR = 53.22 min (minor).
(S)-1-(o-Tolyl)propane-1,3-diol (3h). Following the general
procedure, 3h was obtained in 79% yield (61.7 mg, 0.37 mmol,
colorless oil). The characterization data for 3h were concordant with
that previously reported in the literature.12b Rf = 0.2 (EtOAc/hexane
= 1/1). 1H NMR (500 MHz, CDCl3) δ 7.54−7.53 (m, 1H), 7.25−
7.24 (m, 1H), 7.20−7.13 (m, 2H), 5.22−5.20 (m, 1H), 3.95−3.85
(m, 2H), 2.55 (brs, 1H), 2.38 (brs, 1H), 2.33 (s, 3H), 2.01−1.90 (m,
1H). 13C{1H} NMR (125 MHz, CDCl3) δ 142.3, 134.1, 130.5, 127.3,
126.4, 125.2, 71.0, 61.8, 39.2, 18.9. IR (neat) 3397, 2960, 1487, 1380,
1326, 1124 cm−1. 90% ee was measured by chiral HPLC on an AD-H
column (i-PrOH:hexanes = 5:95, 0.5 mL/min); tR = 44.90 min
(major), tR = 38.59 min (minor).
(S)-1-(Benzofuran-2-yl)propane-1,3-diol (3i). Following the gen-
eral procedure, 3i was obtained in 82% yield (78.6 mg, 0.41 mmol,
colorless oil). The characterization data for 3i were concordant with
that previously reported in the literature.12b Rf = 0.2 (EtOAc/hexane
= 1/1). 1H NMR (500 MHz, CDCl3) δ 7.55 (d, J = 7.5 Hz, 1H), 7.45
(d, J = 8.0 Hz, 1H), 7.28−7.25 (m, 1H), 7.23−7.20 (m, 1H), 6.67 (s,
1H), 5.14−5.11 (m, 1H), 3.97−3.90 (m, 2H), 3.12 (brs, 1H), 2.22−
2.18 (m, 2H), 2.16 (brs, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ
159.0, 154.8, 128.1, 124.2, 122.8, 121.1, 111.2, 102.6, 68.0, 61.0, 36.9.
87% ee was measured by chiral HPLC on an AS-H column (i-
PrOH:hexanes = 5:95, 0.5 mL/min); tR = 29.30 min (major), tR =
34.97 min (minor).
(S)-1-(Thiophen-2-yl)propane-1,3-diol (3j). Following the general
procedure, 3j was obtained in 85% yield (67.1 mg, 0.42 mmol,
colorless oil). The characterization data for 3j were concordant with
that previously reported in the literature.12c Rf = 0.2 (EtOAc/hexane
= 1/1). 1H NMR (500 MHz, CDCl3) δ 7.26−7.25 (m, 1H), 6.99−
6.97 (m, 2H), 5.24−5.21 (m, 1H), 3.94−3.86 (m, 2H), 2.97 (brs,
1H), 2.19 (brs, 1H), 2.16−2.04 (m, 2H). 13C{1H} NMR (125 MHz,
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The Journal of Organic Chemistry
CDCl3) δ 148.3, 126.7, 124.6, 123.5, 70.1, 61.2, 40.7. 88% ee was
measured by chiral HPLC on an AS-H column (i-PrOH:hexanes =
5:95, 0.5 mL/min); tR = 45.76 min (major), tR = 38.82 min (minor).
(S)-3-Phenyl-3-(p-tolyl)propan-1-ol (4). A mixture of Pd2(dba)3 (1
mol %, 0.005 mmol), RuPhos (2 mol %, 0.010 mmol), and KOH (3
equiv, 1.5 mmol) in toluene (1 mL) was stirred for 15 min under an
atmosphere of nitrogen. 2a (1 equiv, 0.5 mmol), 4-bromotoluene (1.5
equiv, 0.75 mmol), THF (1 mL), and H2O (0.2 mL) were added. The
reaction mixture was stirred for 24 h at 70 °C. Upon completion of
the reaction, the reaction mixture was quenched with water and
extracted with ethyl acetate. The combined organic layers were dried
over MgSO4 and concentrated in vacuo. The product was purified by
silica gel chromatography, and 4 was obtained in 80% yield (90.4 mg,
0.40 mmol, colorless oil). The characterization data for 3j were
concordant with that previously reported in the literature.10 Rf = 0.3
(EtOAc/hexane = 1/5). 1H NMR (500 MHz, CDCl3) δ 7.29−7.24
(m, 4H), 7.19−7.14 (m, 3H), 7.10−7.09 (m, 2H), 4.10 (t, J = 8.0 Hz,
1H), 3.63−3.60 (m, 2H), 2.33−2.29 (m, 5H), 1.21 (brs, 1H).
13
C{1H} NMR (125 MHz, CDCl3) δ 144.8, 141.5, 135.8, 129.3,
128.5, 127.8, 127.7, 126.2, 61.2, 47.0, 38.3, 21.0. [α]D20 +10.2 (c 0.52,
CHCl3); [lit.10 (93% ee): [α]D20 +4.3 (c 1.24, CHCl3)]. 90% ee was
measured by chiral HPLC on an AS-H column (i-PrOH:hexanes =
2:98, 1.0 mL/min); tR = 21.59 min (major), tR = 18.99 min (minor).
2-(Cinnamyloxy)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (II). A
mixture of CuCl (5 mol %, 0.025 mmol), (R)-DTBM-Segphos (5.5
mol %, 0.0275 mmol), and NaOt-Bu (10 mol %, 0.05 mmol) in
benzene-d (0.5 mL) was stirred for 5 min in a Schlenk tube under an
atmosphere of nitrogen. Pinacolborane (1.1 equiv, 0.55 mmol) was
added to the reaction mixture, and stirring was continued for another
15 min at room temperature. Substrate 1 dissolved in benzene-d (0.5
mL) was added to the reaction mixture. The reaction mixture was
stirred at 60 °C for 1 h. Aliquot was taken by removing a small
amount of the reaction solution and passing it through a filter, eluting
with benzene-d. The characterization data for II were concordant with
that previously reported in the literature.13 1H NMR (500 MHz,
C6D6) δ 7.18−7.16 (m, 2H), 7.09−7.06 (m, 2H), 7.03−7.01 (m, 1H),
6.61 (d, J = 16.0 Hz, 1H), 6.17 (dt, J = 16.0, 5.5 Hz, 1H), 4.54 (dd, J
= 5.5, 1.5 Hz, 2H), 1.06 (s, 12H). 13C{1H} NMR (125 MHz, C6D6) δ
137.0, 130.6, 128.4, 127.3, 127.2, 126.5, 82.3, 65.2, 24.4.
■
ASSOCIATED CONTENT
* Supporting Information
S Cobalt-Catalyzed Alkene Hydroboration with Pinacolborane. Angew.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.8b03045.
HPLC and NMR spectra of products (PDF)
■
AUTHOR INFORMATION
Corresponding Author
*E-mail: jaesook@skku.edu.
ORCID
Won Jun Jang: 0000-0002-0673-7607
Seung Min Song: 0000-0002-7921-3353
Jaesook Yun: 0000-0003-4380-7878
Author Contributions
†
W.J.J. and S.M.S. contributed equally.
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
This research was supported by a National Research
Foundation of Korea grant (NRF-2016R1A2B4011719),
funded by the Korean government (MEST).
4433
Note
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4434 DOI: 10.1021/acs.joc.8b03045

J. Org. Chem. 2019, 84, 4429−4434