Copper-catalyzed boration of activated alkynes. Chiral boranes via a one-pot copper-catalyzed boration and reduction protocol

Article abstract of DOI:10.1016/j.tet.2011.07.061

Phosphine-copper(I) complexes efficiently catalyzed the mono-boration of electron-deficient alkynes in the presence of MeOH and also catalyzed conjugate reductions of alkenylboronates bearing an electron-withdrawing group. The mono-addition of bis(pinacolato)diboron to alkynes catalyzed by a copper-Xantphos complex produced vinylboronates with high regio and stereoselectivity and asymmetric reduction of the vinylboronates by a chiral copper-bisphosphine catalyst allowed the synthesis of valuable chiral boranes with high enantioselectivity. One-pot boration/asymmetric reduction of α,β-unsaturated alkynoates could be conducted with a single copper-phosphine catalyst.

Full text of DOI:10.1016/j.tet.2011.07.061

Tetrahedron 68 (2012) 3444e3449
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper-catalyzed boration of activated alkynes. Chiral boranes via a one-pot
copper-catalyzed boration and reduction protocol
Ho-Young Jung, Xinhui Feng, Hyohyun Kim, Jaesook Yun *
Department of Chemistry and Institute of Basic Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 June 2011
Received in revised form 7 July 2011
Accepted 21 July 2011
Available online 26 July 2011
Phosphineecopper(I) complexes efficiently catalyzed the mono-boration of electron-deficient alkynes in
the presence of MeOH and also catalyzed conjugate reductions of alkenylboronates bearing an electron-
withdrawing group. The mono-addition of bis(pinacolato)diboron to alkynes catalyzed by a cop-
pereXantphos complex produced vinylboronates with high regio and stereoselectivity and asymmetric
reduction of the vinylboronates by a chiral copperebisphosphine catalyst allowed the synthesis of
valuable chiral boranes with high enantioselectivity. One-pot boration/asymmetric reduction of
unsaturated alkynoates could be conducted with a single copperephosphine catalyst.
a,b-
Keywords:
Boration
Conjugate reduction
Copper
Ó 2011 Elsevier Ltd. All rights reserved.
Asymmetric synthesis
Vinylboronates
1
. Introduction
Vinylboronates are versatile intermediates in organic synthesis,5
and simple vinylboronates can be easily accessed by either con-
6
Transition-metal catalyzed boration reactions of unsaturated
ventional or metal-catalyzed hydroboration reactions of alkynes.
7
CeC bonds can provide a variety of organoboron compounds with
high levels of regio- and stereocontrol. In recent years, the tran-
However, the preparation of electron-deficient vinylboronates by
1
the hydroboration approach is not trivial; only b-boryl acrylates are
sition metal-catalyzed addition of diboron reagents, such as bis(-
pinacolato)diboron (1) and bis(catecholato)diboron to electron-
deficient CeC multiple bonds has received substantial amounts of
attention as an efficient means to prepare functionalized organo-
available by hydroboration of propiolic acid esters with alkylbor-
anes, thus further conversion using pinacolborane is necessary to
8
obtain stable boronates, and a regioselectivity issue arises with
9
alkynoates possessing
a
b
-substituent. Therefore, the de-
2
boron compounds (Scheme 1).
velopment of a general and efficient method for these highly
functionalized compounds is required. We were intrigued by the
possibility of utilizing the catalytic mono-boronate addition to
a
,
b
b
-
-
acetylenic (C^C) substrates to obtain, formally ‘hydroborated’,
10
boryl-a,b-ethylenic products (Scheme 2).
Scheme 1.
b-Boration of a,b-unsaturated (C]C) carbonyl compounds.
Previously, we reported a new copper-catalytic system for the
b-
boration of various -unsaurated (C]C) carbonyl compounds
a,b
3
that included methanol as a reaction promoter. The accelerant role
of methanol could be explained by protonolysis of an organocopper
intermediate (A) to provide a fast catalytic cycle (Scheme 2). As
4
a result of this reaction modification, the substrate scope was
greatly extended from enones to less electrophilic ethylenic esters
and nitriles.
Scheme 2. Proposed catalytic cycle for the copper-catalyzed boration of b-substituted
*
Corresponding author. E-mail address: jaesook@skku.edu (J. Yun).
unsaturated carbonyl compounds in the presence of MeOH.
0
040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.07.061

H.-Y. Jung et al. / Tetrahedron 68 (2012) 3444e3449
3445
In addition to the mono-boration of alkynes, further application
of the resulting alkenylboronates (3) to the synthesis of chiral alkyl
organoboron compounds (4) is delineated in Scheme 3. For the
preparation of chiral boranes, the asymmetric b-boration of a,b-
unsaturated carbonyl compounds has become a useful tool and
several catalytic systems for asymmetric boration including
proceeded in good conversion at room temperature to give exclu-
sively the syn addition product, (Z)-3a. The Xantphos ligand per-
formed better than the DPEphos ligand, since the latter ligand gave
incomplete conversion with concurrent production of w2% of the
0
0
diboration product (3a ). The formation of 3a was even greater
14
with another bidentate phosphine, dppf, under otherwise iden-
tical conditions. Using more than 1.2 equiv of B pin increased the
copper-catalyzed
b
-borations introduced by our group have been
2
2
developed.4
a,11
Alternatively, the same types of chiral alkyl orga-
formation of the diboration product even with the Xantphos ligand.
noboronates could be prepared by asymmetric reduction of alke-
With an optimal reaction protocol using 1.1 equiv of 1, 2 equiv of
nylboronates 3.
MeOH, and Xantphos ligand, various
a,b-alkynyl substrates were
examined in the copper-catalyzed -boration reaction (Table 1).
b
Primary alkyl (2b, 2c, 2e) and secondary alkyl (2d) substituted
acetylenic esters were smoothly converted within 24 h exclusively
to the corresponding (Z)-vinylboronates. Alkyne substrates with
benzoxazole (2f) or phenyl (2h) substitution as the electron-
withdrawing group were also suitable substrates for the reaction,
yielding addition products with high regio- and stereoselectivity.
However, the reaction of ethyl propiolate 2g furnished the syn
addition product in 65% yield due to incomplete conversion. While
Table 1
Synthesis of vinylboronates via copper-catalyzed mono-boration of alkynes
Scheme 3. Synthetic approaches to chiral alkyl boronates.
3 mol % CuCl
R
EWG
6 mol % NaOt-Bu
EWG
+
1
Bpin
3
mol % Xantphos, MeOH (2 equiv)
Copper hydride (CuH) catalysis has proven very efficient for
R
H
THF, rt, 24 h
conjugate reductions12 of a variety of
a
,b
-unsaturated substrates.
13
2
(
Z)-3
However, the asymmetric conjugate reduction of -boryl-
b
a
,
b
-un-
Entry Substrate (2)
Product (3)
Yielda (%)
saturated carbonyl compounds (3) has not previously been repor-
ted. Since phosphineecopper complexes catalyze both boration
and reduction reactions, we initially investigated the conjugate
reduction of 3 and then the one-pot reaction to produce the chiral
boron compounds 4 from the corresponding alkynes using a single
copper-complex as catalyst. In this paper, we present details of our
recent studies on these topics.
O
n-C H
O
6
13
1
(Z)-3b 93
OEt 2b
Bpin
OEt
n-C
H
H
6
13
Cy
O
O
O
2
88
OEt 2c
Z)-3c
(
Bpin
OEt
OEt
OEt
CyH C
2
2
. Results and discussion
2
H
H
.1. Copper-catalyzed mono
b-boration of alkynoates;
O
Cy
synthesis of electron-deficient alkenylboronates
3
(Z)-3d 99
OEt 2d
Bpin
Cy
To check the feasibility of the proposed mono-boron addition
approach, we chose ethyl 2-butynoate (2a) as a model substrate and
THPO
Bpin
O
O
4b
77
DPEphos and Xantphos as ligands on the basis of their efficiency in
(
Z)-3e
3
OEt 2e
the
b
-boration of ethyl crotonate. By employing a catalytic amount
THPO
H
2 2
of copper salt and ligand in the presence of 1.1 equiv of B pin in THF,
various reaction conditions were examined (Scheme 4). The reaction
without the methanol additive showed no appreciable conversion at
room temperature. A moderate conversion (64%) and yield were
N
CH
3
N
5
H C
2f
82
3
Bpin
O
(Z)-3f
O
ꢀ
obtained with an increased reaction temperature(70 C).
H
Fortunately, addition of methanol greatly enhanced the reaction
rate, and the reactions with either DPEphos or Xantphos ligand
O
H
O
6c
(E)-3g 65
OEt
2g
Bpin
OEt
H
H
H
H
Ph
7d
Ph
99
71
2h
(E)-3h
Bpin
H
O
(
Z)-3i + (E)-3i
34 : 66)
8
OEt 2i
(
t-Bu
a
Isolated yield.
b
c
(
Z)-3e:protodeboronated product¼87:13 by GC and NMR analysis.
0% Conversion.
With DPEphos ligand instead of Xantphos ligand.
9
d
Scheme 4. Optimization.

3446
H.-Y. Jung et al. / Tetrahedron 68 (2012) 3444e3449
the examples shown in Table 1 are highly stereoselective, the tert-
butyl substituted ester 2b produced a mixture of (E)- and (Z)-iso-
mers presumably as a result of equilibration of the coppereenolate
intermediates15 during the catalytic cycle.
Suitable levels of regioselective mono-boration could not be
obtained for aryl-substituted alkynoates and alkynones under our
reaction conditions, which employed a limited amount of bis(pi-
nacolato)diboron (Fig. 1). Regioselectivity was problematic with
aryl-substituted alkynoates and alkynones, and double boration
was significant with active alkynones; thus reactions of these
substrates furnished mixtures of organoboron products along with
unreacted starting material.
Asymmetric hydrosilylations of vinylboronate (Z)-3a were con-
ducted with an in situ generated catalyst by combining 3 mol %
CuCl, 6 mol % NaOt-Bu, and 3 mol % ligand in THF, followed by the
addition of polymethylhydrosiloxane (PMHS) and t-BuOH. Five
representative chiral ligands were screened for their effectiveness,
and the results are described in Scheme 5.
The enantiomeric excess and absolute stereochemistry of the
product (4a) from each reaction were determined byconverting it to
19
the corresponding b-hydroxy ester by oxidation. The conjugate
reductions with (R,R)-QuinoxP or (S,S)-Me-Duphos as the ligand
were not highly enantioselective for the model substrate, producing
the product with only 27% ee and 14% ee, respectively. However, the
Josiphos, DTBM-segphos, and p-Tolbinap ligands were very effective
in forming the chiral boron product 4a with excellent enantiose-
lelctivities (>95% ee) in good yield. Next, we carried out the re-
duction of benzoxazole-substituted vinylboronate, (Z)-3f under the
same catalytic conditions in THF using PMHS as the hydrosilane
source. The reduction furnished the product 4f in 96% ee. In com-
Fig. 1. Some of the unsuitable alkyne substrates for the copper-catalyzed b-boration
with MeOH.
parison, the reaction using 5 mol % Cu(OAc)
2 2
$H O in the presence of
2
0
PhSiH as the stoichiometric reducing agent in toluene gave
3
a similar enantioselectivity, 98% ee (Scheme 6).
2
.2. Copper-catalyzed conjugate reduction of
alkenylboronates
Chiral boron compounds are valuable building blocks in organic
synthesis. CꢁB bonds can be converted into a CꢁN or CꢁO functio-
5
a,5d,16
nality
with retention of configuration and their role in asym-
17
metric CꢁC bond forming reactions has seen a recent significant
increase.
As described in Scheme 3, an alternative strategy for asymmetric
b-boration is the conversion of b-borylated-a,b-unsaturated (C]C)
carbonyl compounds to chiral boranes using a chiral CuH catalyst.
While several asymmetric hydrogenations of vinylboronates using
18
either Rh or Ir catalysts have been reported in the literature,
analogous CuH-catalyzed enantioselective reductions have not yet
been reported. Starting materials in this investigation should be
geometrically pure since the reduction of (E)- and (Z)-isomers
Scheme 6. CuH reductions of 3f.
13
would result in the formation of opposite enantiomers.
2.3. One-pot sequential
alkynoates
b-boration/reduction reactions of
The success of this reduction approach to prepare chiral boranes
increased the likelihood of one-pot sequential -boration and re-
b
duction reactions with a single copper-catalytic species. Since the
copper-catalyzed boration produces geometrically pure vinyl-
boronates, no chromatographic purification would be necessary for
the subsequent CuH reduction.
Nonetheless, chiral bisphosphine ligands have not been pre-
viously employed for the mono-boration of alkynoates, and thus,
we next investigate the proper mono-boration conditions with
the active bisphosphine ligands. Fortunately, with a limited
2 2
amount of MeOH (1 equiv) and B pin (1 equiv) in the presence of
the Josiphos ligand, the reaction of ethyl 2-butynoate (2a) was
complete in 7 h, and only a small amount of the diboration
0
product (3a ) was detected by GC analysis. The following addition
of 1.5 equiv of PMHS and t-BuOH to the reaction mixture fur-
nished the desired reduction product in 80% overall yield with
9
3% enantioselectivity (Scheme 7). In an attempt to improve the
selectivity of the boration and to simplify the addition sequence,
we employed 4 equiv of t-BuOH instead of MeOH; however, only
a low conversion of the starting material was observed. Neither
the Me-Duphos nor DTBM-segphos ligands gave a good conver-
sion in the second reduction step under these one-pot sequential
reaction conditions.
More examples were examined using the chiral Josiphos ligand
as the optimal ligand (Scheme 8). After the boration of alkynoates
(2) was complete (12e24 h), subsequent addition of PMHS and
Scheme 5. Results using representative chiral bisphosphine ligands with CuH.

H.-Y. Jung et al. / Tetrahedron 68 (2012) 3444e3449
3447
3. Conclusions
In summary, we have shown that phosphineecopper(I) com-
plexes efficiently catalyze the mono-boration of electron-deficient
alkynes in the presence of MeOH to afford vinylboronates. A
coppereXantphos complex leads to the successful mono-addition
of bis(pinacolato)diboron to active alkynes, such as
a,b-un-
saturated alkynoates with high regio- and stereoselectivity under
mild reaction conditions. Copper-hydride catalyzed asymmetric
reduction of the resulting vinylboronates has been carried out
employing a chiral copperebisphosphine catalyst, and the one-
pot boration/asymmetric reduction of
a,b-unsaturated alky-
noates has been investigated with a single copperephosphine
catalyst. These reactions furnished valuable chiral boranes with
high enantioselectivity.
4
4
. Experimental section
Scheme 7. One-pot boration/reduction of 2a.
.1. General information
THF was distilled from sodium benzophenone ketyl under ni-
t-BuOH led to the formation of the desired chiral
b-borylated esters
trogen. CuCl, NaOt-Bu, bis(pinacolato)diboron, and other commer-
cial substrates were purchased from Aldrich and used as received.
All reactions were carried out under nitrogen atmosphere, in an
oven-dried Schlenk tube and run two or more times. Flash chro-
4
. The reaction of primary alkyl-substituted alkynoates (2b, 2c,
and 2j) furnished the products in 24 h with good overall isolated
yield and enantioselectivity. The secondary isopropyl substituted
substrate 2k gave a moderate enantioselectivity, reflecting the
matography was performed on silica gel from Fuji Silysia Chemical
smaller steric difference between the b-substituents of the alke-
1
(
70e230 mesh). All H NMR spectra were obtained on Varian
nylboron intermediates. However, the benzoxazole substituted
alkyne 2f did not proceed in good enantioselectivity in opposition
to our expectation. It turned out that the first boration step with
the Josiphos ligand gave a mixture of (Z) and (E)-isomers (56:43)
in contrast to the Xantphos ligand, which afforded only the (Z)-
isomer in a geometrically pure form (entry 5, Table 1). Accord-
ingly, this one-pot sequence is less appropriate for the benzox-
azole alkyne than the separate procedures using two different
copper catalystic systems with chromatographic separation of the
intermediate vinylboronates.
Mercury 300 systems and reported in parts per million (ppm)
13
downfield from tetramethylsilane. C NMR spectra are reported in
ppm referenced to deuteriochloroform (77.16 ppm). Infrared
spectra (IR) were obtained on Nicolet FT-IR instrument and recor-
ꢁ
1
ded in cm . HPLC and GC analysis were performed on a Younglin
Acme 9000 series and Younglin Acme 6000 Series. High resolution
mass spectra (HRMS) were obtained at Korea Basic Science Institute
21
(
Daegu, Korea) and reported in the form of m/z (intensity relative to
base peak¼100). Optical rotations were measured with a Per-
kineElmer 343 plus Polarimeter.
4.2. General procedure for the mono
b-boration of
alkynoates
CuCl (1.5 mg, 0.015 mmol), NaOt-Bu (2.9 mg, 0.03 mmol), and
Xantphos ligand (8.7 mg, 0.015 mmol) were placed in an oven-
dried Schlenk tube under nitrogen and THF (0.45 mL) were
added. The reaction mixture was stirred for 30 min at room tem-
perature and then bis(pinacolato)diboron (127 mg, 0.5 mmol) in
THF (0.3 mL) was added. The reaction mixture was stirred for
10 min and
a,
b-acetylenic ester 2 (0.5 mmol) was added, followed
by MeOH (40
mL, 1 mmol). The reaction tube was washed with
further THF (0.2 mL), sealed, and stirred until no starting material
was detected by TLC. The reaction mixture was filtered through
a pad of Celite and concentrated. The product was purified by silica
gel chromatography.
4
2
4
.2.1. (Z)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-
1
3
-enoate (3a). Yield (85%); H NMR (300 MHz, CDCl ) d 6.45 (1H, s),
13
.18 (2H, q, J¼6.9 Hz), 2.17 (3H, s), 1.30e1.20 (15H, m); C NMR
(75.4 MHz, CDCl
3
)
d
166.0, 147.0 (CeB), 130.5, 84.0, 60.0, 24.7, 16.2,
þ
14.2; EIMS m/z (rel intensity) 241 (M , 100), 195 (33), 111 (18).
4
2
4
.2.2. (Z)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oct-
1
3
-enoate (3b). Yield (93%); H NMR (300 MHz, CDCl ) d 6.40 (1H, s),
.17 (2H, q, J¼7.1 Hz), 2.66 (2H, t, J¼7.2 Hz), 1.34e1.27 (23H, m), 0.87
13
(3H, t, J¼6.6 Hz); C NMR (75.4 MHz, CDCl
3
) d 165.9, 162.0 (CeB),
Scheme 8.
129.8, 84.0, 59.6, 31.8, 30.0, 29.6, 29.5, 24.7, 14.3, 14.1; EIMS m/z (rel

3448
H.-Y. Jung et al. / Tetrahedron 68 (2012) 3444e3449
þ
intensity) 311 (M , 32), 265 (14), 210 (100), 181 (56), 167 (33), 83
13).
anhydrous THF (0.5 mL) was stirred for 10 min in a Schlenk tube
under an atmosphere of nitrogen. PMHS (72 L, 1.2 mmol) was
(
m
added to the reaction mixture and stirring was continued for
10 min at room temperature for catalyst activation. Alkenylbor-
onate (0.5 mmol) was added, followed by t-BuOH (153 mL,
4
2
.2.3. (Z)-Ethyl 4-cyclohexyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
1
-yl)but-2-enoate (3c). Yield (88%); H NMR (300 MHz, CDCl
3
)
d
6.44
(
1H, s), 4.16 (2H, q, J¼7.2 Hz), 2.58 (2H, d, J¼7.0 Hz), 1.72e1.40 (6H,
1.6 mmol). The reaction tube was washed with further THF
(0.4 mL), sealed, and stirred for 24 h. The reaction mixture was
quenched with aqueous ammonium chloride (1 mL) for 10 min.
The aqueous layer was extracted with diethyl ether (3ꢂ5 mL) and
13
m), 1.30e1.18 (5H, m), 1.27 (12H, s), 0.98 (3H, t, J¼7.2 Hz); C NMR
(
3
3
75.4 MHz, CDCl
3.4, 26.6, 26.5, 24.7, 14.3; HRMS (EI ) m/z calculated for C18
3
)
d
166.0, 151.7 (CeB), 130.4, 84.0, 59.8, 38.9, 37.2,
þ
4
H31BO :
22.2315, found: 322.2318.
4
the combined organic layers were dried over MgSO , and
concentrated in vacuo. The product was purified by silica gel
4
.2.4. (Z)-Ethyl 3-cyclohexyl-3-(4,4,5,5-tetramethyl-1,3,2-
chromatography.
1
dioxaborolan-2-yl)acrylate (3d). Yield (99%); H NMR (300 MHz,
CDCl
3
)
d
6.24 (1H, s), 4.16 (2H, q, J¼7.2 Hz), 1.74e1.65 (5H, m),
4.4. General procedure for the one-pot boration/reduction of
a,b-acetylenic esters
13
1.55e1.48 (6H, m), 1.30e1.25 (15H, m); C NMR (75.4 MHz, CDCl
3
)
d
166.1,158.0 (CeB),127.9, 83.9, 59.8, 40.0, 31.5, 26.4, 26.1, 24.8,14.4;
þ
EIMS m/z (rel intensity) 309 (M , 12), 208 (100), 180 (32), 112 (13).
CuCl (1.5 mg, 0.015 mmol), NaOt-Bu (2.9 mg, 0.03 mmol), and
R,S)-Josiphos ligand (9.6 mg, 0.015 mmol) were placed in an
(
4
.2.5. (Z)-Ethyl 4-(tetrahydro-2H-pyran-2-yloxy)-3-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)but-2-enoate (3e). Colorless oil,
7% yield; 1H NMR (300 MHz, CDCl
6.29 (1H, s), 4.81 (1H, dd,
J¼12.3, 2.1 Hz), 4.71e4.61 (2H, m), 4.17 (2H, q, J¼7.2 Hz), 3.96e3.88
1H, m), 3.57e3.47 (1H, m), 1.90e1.47 (6H, m), 1.42e1.24 (15H, m);
irradiation of the vinylic proton at 6.29 ppm resulted in no en-
oven-dried Schlenk tube and THF (0.45 mL) were added under
nitrogen. The reaction mixture was stirred for 30 min at room
temperature and then, bis(pinacolato)diboron (127 mg,
0.5 mmol) and THF (0.3 mL) were added. The reaction mixture
was stirred for 10 min and an alkyne (2) (0.5 mmol) was added,
7
3
) d
(
followed by MeOH (20
washed with THF (0.2 mmol), sealed, and stirred until no starting
material was detected by TLC or GC. PMHS (45 L, 0.75 mmol)
and t-BuOH (71.6 L, 0.75 mmol) were added to the reaction
mL, 0.5 mmol). The reaction tube was
1
3
3
hancement of the allylic proton signal; C NMR (75.4 MHz, CDCl )
d
165.6, 150.0 (CeB), 128.5, 98.2, 84.0, 65.7, 61.4, 60.1, 30.4, 25.5, 24.7,
m
þ
19.0, 14.2; HRMS (EI ) m/z calculated for C17
6
H29BO : 340.2057,
m
found: 340.2057.
mixture and stirring was continued. After completion, the re-
action mixture was quenched with aqueous ammonium chloride
(1 mL) and stirred for 10 min. The aqueous layer was extracted
with diethyl ether (3ꢂ5 mL) and the combined organic layers
4.2.6. (Z)-2-(2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)prop-1-
ꢁ
1
enyl)benzo[d]oxazol (3f). Yellow solid, 82% yield;
n
max cm 2977,
1
200, 1080; 1H NMR (300 MHz, CDCl
3
)
d
7.80e7.72 (1H, m),
4
were dried over MgSO , and concentrated in vacuo. The product
7
.55e7.48 (1H, m), 7.34e7.30 (2H, m), 7.14 (1H, d, J¼1.6 Hz), 2.42
was purified by silica gel chromatography.
13
(
1
3H, d, J¼1.6 Hz), 1.31 (12H, s); C NMR (75.4 MHz, CDCl
3
) d 162.4,
50.0, 142.0, 126.2, 125.3, 124.4, 120.3, 110.6, 84.2, 24.9, 17.3; HRMS
4.4.1. (R)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)buta-
þ
ꢁ1
(
EI ) m/z calculated for C16
H20BNO
3
: 285.1536, found: 285.1533.
noate (4a). Colorless oil, 80% yield;
n
max cm 2979, 1730, 1200,
1
1
140; H NMR (300 MHz, CDCl
3
)
d
4.12 (2H, q, J¼7.2 Hz), 2.40 (2H, t,
4.2.7. (E)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acry-
J¼7.8 Hz), 1.41e1.34 (1H, m), 1.27e1.22 (15H, m), 1.00 (3H, d,
1
13
late (3g). Yield (65%); H NMR (300 MHz, CDCl
3
)
d
6.78 (1H, d,
J¼7.5 Hz); C NMR (75.4 MHz)
d 173.9, 83.4, 60.4, 38.0, 25.1, 25.0,
J¼18.3 Hz), 6.62 (1H, d, J¼18.3 Hz), 4.21 (2H, q, J¼7.2 Hz), 1.35e1.24
15.5, 14.7, 13.8 (CeB); Enantiomeric excess and absolute configu-
(
15H, m); 13C NMR (75.4 MHz, CDCl
3
)
d
166.0, 138.8, 134.1 (CeB),
ration were determined with the corresponding acetate derivative
þ
8
4.1, 60.6, 24.8, 14.2; EIMS m/z (rel intensity) 227 (M , 100), 211
of the
b-hydroxy compound obtained by oxidation. 95% ee was
(
42), 182 (11), 127 (6), 111 (31).
determined by GC analysis on a Beta-Dex column; (S)-isomer
2
0
t
R
¼30.3 min, (R)-isomer t
R
¼30.9 min. ½
a
ꢃ
þ2.29 (c 0.1, CHCl
3
)
D
2
2
25
D
4
.2.8. (E)-4,4,5,5-Tetramethyl-2-styryl-1,3,2-dioxaborolane
[lit.
½
a
ꢃ
þ2.9 (c 1.0, CHCl
3
), 98% ee (R)].
1
3
(3h). Yield (99%); H NMR (300 MHz, CDCl ) d 7.51e7.30 (6H, m),
13
6
CDCl
.17 (1H, d, J¼18.3 Hz), 1.38e1.25 (12H, m); C NMR (75.4 MHz,
4.4.2. (R)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)octa-
1
3
)
d
149.6, 137.4, 129.0, 128.6, 127.1, 116.2 (CeB), 83.3, 24.8;
noate (4b). Colorless oil, 82% yield; H NMR (300 MHz, CDCl
3
)
þ
EIMS m/z (rel intensity) 230 (M , 47), 215 (21), 144 (100), 131 (23),
7
d
4.14e4.06 (2H, m), 2.44e2.35 (2H, m), 1.46e1.22 (24H, m), 0.86
13
7 (6).
(3H, t, J¼7.0 Hz); C NMR (75.4 MHz)
0.6, 28.5, 24.9, 24.8, 22.7, 14.4, 14.2; Enantiomeric excess and ab-
solute configuration were determined with the corresponding
hydroxy compound. 90% ee was determined by HPLC analysis on an
OD-H column; (hexane/i-PrOH¼95:5, ¼210 nm, 0.5 mL/min), (R)-
d 174.2, 83.2, 60.3, 35.9, 32.1,
3
4
.2.9. (E)-Ethyl 4,4-dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-
b-
dioxaborolan-2-yl)pent-2-enoate (3i). Yield (71%) ((E) and (Z)-iso-
mer). The major (E)-isomer was characterized as the following; H
1
l
2
0
NMR (300 MHz, CDCl
.21e1.29 (24H, m); NOE measurement: irradiation of the vinylic
proton at 6.23 ppm resulted in a 3.4% enhancement of the tert-butyl
3
)
d
6.23 (1H, s), 4.17 (2H, q, J¼7.2 Hz),
isomer t
CHCl ). [lit.
R
¼9.00 min, (S)-isomer t
R
¼9.67 min. ½
a
ꢃ
ꢁ22.0 (c 0.1,
D
2
3
24
D
1
3
½
a
ꢃ
ꢁ21 (c 0.99, CHCl
3
) (R)].
13
proton signal at 1.24 ppm; C NMR (75.4 MHz, CDCl
(
3
)
d
168.9,152.0
4.4.3. Ethyl 4-cyclohexyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
þ
1
CeB), 128.1, 83.7, 60.4, 36.1, 29.6, 25.0, 14.1; HRMS (EI ) m/z cal-
2-yl)butanoate (4c). Colorless oil, 92% yield; H NMR (300 MHz,
culated for C15
H
27BO
4
: 288.2002, found: 288.2004.
CDCl
3
)
d
4.11 (2H, q, J¼7.2 Hz), 2.4 (2H, d, J¼7.8 Hz), 1.79e1.58 (3H,
13
m), 1.46 (1H, m), 1.28e1.18 (22H, m), 0.84 (3H, t, J¼7.2 Hz); C NMR
4
.3. General procedure for the copper-catalyzed conjugate
(75.4 MHz CDCl
3
)
d
174.1, 83.2, 60.3, 38.2, 37.2, 36.4, 33.3, 26.5, 25.8,
þ
reduction of alkenylboronates
24.8, 24.0 14.4; HRMS (ESI ) calculated for C18
H33BO
4
: 324.2472,
found: 324.2475; Enantiomeric excess (85%) was determined by
HPLC analysis on an OD-H column with the corresponding -hy-
droxy compound; (hexane/i-PrOH¼95:5, ¼210 nm, 0.5 mL/min),
A mixture of CuCl (1.2 mg, 0.012 mmol), NaOt-Bu (2.5 mg,
.024 mmol), and (R,S)-Josiphos ligand (7.7 mg, 0.012 mmol) in
b
0
l

H.-Y. Jung et al. / Tetrahedron 68 (2012) 3444e3449
3449
2
0
major isomer t
R
¼8.8 min, minor isomer t
R
¼9.7 min. ½
a
ꢃ
ꢁ12.7 (c
B. C.; Das, S. Tetrahedron Lett. 2002, 43, 2323e2325; (h) Ni: Hirano, K.; Yor-
imitsu, H.; Oshima, K. Org. Lett. 2007, 9, 5031e5033; (i) NHC: Lee, K.; Zhugralin,
A. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 7253e7255.
D
0
.54 CHCl
3
).
3
. Mun, S.; Lee, J.-E.; Yun, J. Org. Lett. 2006, 8, 4887e4889.
4
2
1
.4.4. (R)-Ethyl 5-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
4. For experimental evidence and related DFT calculations, see: (a) Sim, H.-S.;
Feng, X.; Yun, J. Chem.dEur. J. 2009, 15, 1939e1943; (b) Dang, L.; Lin, Z.; Marder,
T. B. Organometallics 2008, 27, 4443e4454.
ꢁ1
-yl)pentanoate (4j). Colorless oil, 85% yield;
7.29e7.14 (5H, m), 4.11 (2H, q,
J¼7.2 Hz), 2.65 (2H, dd, J¼7.2, 1.8 Hz), 2.46 (2H, dd, J¼4.8, 3.6 Hz),
.83e1.76 (1H, m), 1.70e1.60 (1H, m), 1.47e1.38 (1H, m), 1.29e1.19
15H, m); 13C NMR (75.4 MHz, CDCl
173.9, 142.6, 128.5, 128.4,
25.8, 83.3, 60.3, 35.8, 35.2, 32.7, 25.0, 24.8, 19.9 (CeB), 14.4; HRMS
nmax cm 2976, 1726,
143; 1H NMR (300 MHz, CDCl
) d
3
5
. (a) Shade, R. E.; Hyde, A. M.; Olsen, J.-C.; Merlic, C. A. J. Am. Chem. Soc. 2010, 132,
1202e1203; (b) Wang, Q.; Finn, M. G. Org. Lett. 2000, 2, 4063e4065; (c) Jeon, S.-
J.; Chen, Y. K.; Walsh, P. J. Org. Lett. 2005, 7, 1729e1732; (d) Hupe, E.; Marek, I.;
Knochel, P. Org. Lett. 2002, 4, 2861e2863; (e) Schl u€ ter, A. D. J. Polym. Sci., Part A:
1
(
1
3
) d
Polym. Chem. 2001, 39, 1533e1556; (f) Stefani, H. A.; Cella, R.; Vieira, A. S. Tet-
rahedron 2007, 63, 3623e3658.
6. (a) Ohmura, T.; Yamamoto, Y.; Miyaura, N. J. Am. Chem. Soc. 2000, 122,
þ
(
ESI ) calculated for C19
tiomeric excess (90%) was determined by HPLC analysis on an OD-H
column with the corresponding -hydroxy compound; (hexane/i-
PrOH¼95:5, ¼254 nm, 0.5 mL/min), (S)-isomer t ¼18.0 min, (R)-
isomer t
¼20.7 min. ½
CHCl ), 98% ee (S)].
4
H29BO : 332.2159, found: 332.2162; Enan-
4990e4991; (b) Tucker, C. E.; Davidson, J.; Knochel, P. J. Org. Chem. 1992, 57,
3482e3485; (c) Pereira, S.; Srebnik, M. Organometallics 1995, 14, 3127e3128;
b
(d) Pereira, S.; Srebnik, M. Tetrahedron Lett. 1996, 37, 3283e3286; (e) Wang, Y.
D.; Kimball, G.; Prashad, A. S.; Wang, Y. Tetrahedron Lett. 2005, 46, 8777e8780;
(f) Gridnev, I. D.; Miyaura, N.; Suzuki, A. Organometallics 1993, 12, 589e592.
l
R
½
2
0
24
24
D
R
a
ꢃ
D
ꢁ0.9 (c 0.8, CHCl
3
) [lit.
a
ꢃ
þ1.3 (c 1.0,
7
. A palladium-catalyzed cross coupling of diboron with vinyl triflates provides
another route to electron-deficient vinylboronates, see: (a) Ishiyama, T.; Takagi,
J.; Kamon, A.; Miyaura, N. J. Organomet. Chem. 2003, 687, 284e290; (b) Takagi,
J.; Takahashi, K.; Ishiyama, T.; Miyaura, N. J. Am. Chem. Soc. 2002, 124,
3
4
.4.5. Ethyl 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
8001e8006.
1
yl)pentanoate (4k). Colorless oil, 76% yield; H NMR (300 MHz,
CDCl
4.08 (2H, m), 2.45 (1H, dd, J¼10.7, 5.7 Hz), 2.34 (1H, dd,
8. (a) Negishi, E.-i.; Yoshida, T. J. Am. Chem. Soc. 1973, 95, 6837e6838; (b) Marti-
nez-Fresneda, P.; Vaultier, M. Tetrahedron Lett. 1989, 30, 2929e2932.
3
) d
9. Plamondon, J.; Snow, J. T.; Zweifel, G. Organomet. Chem. Synth. 1971, 1, 249e252.
J¼10.8, 5.7 Hz), 1.80e1.69 (1H, m), 1.30e1.16 (16H, m), 0.91 (6H, q,
10. Lee, J.-E.; Kwon, J.; Yun, J. Chem. Commun. 2009, 5996e5998.
4
2
.0 Hz); 13C NMR (75.4 MHz CDCl
7.1, 24.9, 24.7, 22.9, 21.7 (CeB), 14.3; HRMS (ESI ) calculated for
3
)
d
174.4, 83.1, 60.2, 33.9, 29.2,
11. For asymmetric catalysis, (a) Cu: Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed. 2008, 47,
þ
145e147; (b) Chea, H.; Sim, H.-S.; Yun, J. Adv. Synth. Catal. 2009, 351, 855e858; (c)
Feng, X.; Yun, J. Chem. Commun. 2009, 6577e6579; (d) Feng, X.; Yun, J. Chem.
dEur. J. 2010,16,13609e13612; (e) Lillo, V.; Prieto, A.; Bonet, A.; Díaz-Requejo, M.
M.; Ramírez, J.; P eꢀ rez, P. J.; Fern aꢀ ndez, E. Organometallics 2009, 28, 659e662; (f)
Chen, I.-H.; Yin, L.; Itano, W.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2009, 131,
11664e11665; (g) O’Brien, J. M.; Lee, K.; Hoveyda, A. H. J. Am. Chem. Soc. 2010,132,
14 4
C H27BO : 270.2002, found: 270,1997; Enantiomeric excess (56%)
was determined by GC Beta-Dex column and optical rotation was
measured with the corresponding acetate derivative; minor isomer
2
0
t
R
¼45.5 min, major isomer t
R
¼46.9 min. ½
a
ꢃ
ꢁ12.7 (c 0.54 CHCl
3
).
D
10630e10633; (h) Rh: Shiomi, T.; Adachi, T.; Toribatake, K.; Zhou, L.; Nishiyama,
H. Chem. Commun. 2009, 5987e5989; (i) Ni: Lillo, V.; Geier, M. J.; Westcott, S. A.;
4
.4.6. 2-(2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)
Fern aꢀ ndez, E. Org. Biomol. Chem. 2009, 7, 4674e4676; (j) Phosphine: Bonet, A.;
1
ꢀ
ꢀ
Gulyas, H.; Fernandez, E. Angew. Chem., Int. Ed. 2010, 49, 5130e5134.
benzo[d]oxazole (4f). Yellow oil, 86% yield; H NMR (300 MHz,
CDCl 7.69e7.57 (1H, m), 7.50e7.36 (1H, m), 7.32e7.18 (2H, m),
.06 (1H, dd, J¼15.8, 7.5 Hz), 2.91 (1H, dd, J¼15.8, 7.5 Hz), 1.72e1.63
1
2. (a) Appella, D. H.; Moritani, Y.; Shintani, R.; Ferreira, E. M.; Buchwald, S. L. J. Am.
Chem. Soc. 1999, 121, 9473e9474; (b) Lipshutz, B. H.; Noson, K.; Chrisman, W. J.
Am. Chem. Soc. 2001, 123, 12917e12918; (c) Czekelius, C.; Carreira, E. M. Angew.
Chem., Int. Ed. 2003, 42, 4793e4795; (d) Lee, D.; Kim, D.; Yun, J. Angew. Chem.,
Int. Ed. 2006, 45, 2785e2787; (e) Yoo, K.; Kim, H.; Yun, J. Chem.dEur. J. 2009, 15,
3
) d
3
13
(
(
1H, m), 1.23 (6H, s), 1.21 (6H, s), 1.09 (3H, d, J¼7.5 Hz); C NMR
75.4 MHz, CDCl
3
)
d
167.4, 150.8, 141.4, 124.2, 119.4, 110.2, 83.4, 31.7,
1
1134e11138; (f) Llamas, T.; Array ꢀa s, R. G.; Carretero, J. C. Angew. Chem., Int. Ed.
007, 46, 1e5; (g) Desrosiers, J.-N.; Charette, A. B. Angew. Chem., Int. Ed. 2007,
46, 5955e5957; (h) Deutsch, C.; Krause, N.; Lipshutz, B. H. Chem. Rev. 2008, 108,
916e2927.
3. With an alkynoester, double reduction was reported to form the saturated ester
derivative with CuH, see: Lipshutz, B. H. Synlett 2009, 509e524.
þ
2
4.7, 24.6, 15.3; HRMS (ESI ) calculated for C16
H22BNO
3
: 287.1693,
2
found: 287.1694; Enantiomeric excess (9%) was determined by
HPLC analysis on an OD-H column with the corresponding -hy-
droxy compound; (hexane/i-PrOH¼99:1, ¼254 nm, 0.5 mL/min),
minor isomer t ¼26.7 min.
¼24.9 min, major isomer t
2
b
1
l
0
14. Dppf¼1,1-bis(diphenylphosphino)ferrocene. The ratio of 3a and 3a was 77:23
R
R
in 90% conversion.
1
5. (a) Corey, E. J.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1969, 91, 1851e1852; (b)
Acknowledgements
For anti-addition examples in copper-mediate additions when t-Bu is involved:
Gil, J. M.; Oh, D. Y. J. Org. Chem. 1999, 64, 2950e2953; (c) Kim, H. R.; Yun, J.
Chem. Commun. 2011, 2943e2945.
We thank the National Research Foundation for financial sup-
port (R01-2008-000-20332-0, NRF-20090085824 and NRF-
16. (a) Matteson, D. S. Chem. Rev. 1989, 89, 1535e1551; (b) Crudden, C. M.; Edwards,
D. Eur. J. Org. Chem. 2003, 4695e4712.
2
0110009533). We are grateful to Solvias for a generous gift of (R,S)-
17. (a) Imao, D.; Glasspoole, B. W.; Laberge, V. S.; Crudden, C. M. J. Am. Chem. Soc.
2009, 131, 5024e5025; (b) Ros, A.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2009,
Josiphos.
48, 6289e6292; (c) Ohmura, T.; Awano, T.; Suginome, M. J. Am. Chem. Soc. 2010,
1
32, 13191e13193; (d) Sandrock, D. L.; Jean-G eꢀ rard, L.; Chen, C.; Dreher, S. D.;
Molander, G. A. J. Am. Chem. Soc. 2010, 132, 17108e17110.
8. (a) Ueda, M.; Saitoh, A.; Miyaura, N. J. Organomet. Chem. 2002, 642, 145e147; (b)
Moran, W. J.; Morken, J. P. Org. Lett. 2006, 8, 2413e2415; (c) Paptchikhine, A.;
Cheruku, P.; Engman, M.; Andersson, P. G. Chem. Commun. 2009, 5996e5998;
References and notes
1
1
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(
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(
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ꢁ
23. Nagai, K.; Doi, T.; Sekiguchi, T.; Namatame, L.; Sunazuka, T.; Tomoda, H.; Omura,
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