Asymmetric β-boration of α,β-unsaturated carbonyl compounds with chiral Rh[bis(oxazolinyl)phenyl] catalysts

Article abstract of DOI:10.1016/j.tet.2013.02.086

Chiral rhodium[bis(oxazolinyl)phenyl] complexes exhibited high catalytic activity for the β-boration of α,β-unsaturated esters, ketones, and amides with bis(pinacolato)diboron in the presence of sodium tert-butoxide to attain high enantioselectivity of up to 97%. The substrate scope and catalytic mechanism were discussed.

Full text of DOI:10.1016/j.tet.2013.02.086

Tetrahedron 69 (2013) 3551e3560
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Asymmetric b-boration of a,b-unsaturated carbonyl compounds
with chiral Rh[bis(oxazolinyl)phenyl] catalysts
*
Kenji Toribatake, Li Zhou, Ayae Tsuruta, Hisao Nishiyama
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral rhodium[bis(oxazolinyl)phenyl] complexes exhibited high catalytic activity for the b-boration of
Received 6 December 2012
Received in revised form 20 February 2013
Accepted 23 February 2013
Available online 28 February 2013
a,b-unsaturated esters, ketones, and amides with bis(pinacolato)diboron in the presence of sodium tert-
butoxide to attain high enantioselectivity of up to 97%. The substrate scope and catalytic mechanism
were discussed.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric
Rhodium
Bis(oxazoline)
Boration
Conjugate addition
1. Introduction
In 2008, Yun et al. reported the asymmetric b-boration of a,b-un-
saturated nitriles and esters using a copper-chiral ferrocenylphosphine
catalyst and bis(pinacolato)diboron (B2pin2) to obtain 94% ee and 91%
ee with cinnamonitriles and cinnamates, respectively.8a Yun et al. then
Organoboronic acid derivatives have been examined as important
precursors for organic transformation.1 Especially, diborons can cat-
alytically add to alkenes and alkynes via metaleboryl intermediates
to provide a variety of useful functionalized compounds.2 In 1993,
Suzuki and Miyaura disclosed that addition of diborons to alkenes
and alkynes can efficiently be promoted by Pt catalysts.3 In the case of
extended the asymmetric boration to a,b-unsaturated ketones, am-
ides, and cyclic carbonyl compounds as substrates including synthesis
of functionalized chiral tertiary carbon skeletons.8bee In 2009, Perez
ꢀ
ꢀ
and Fernandez demonstrated that chiral Cu(N-hetereocarbene, NHC)
a
,
b
-unsaturated carbonyl compounds, the conjugate boration can
also be catalyzed by Pt,4 Rh,5 Cu,6 Ni,7a,b and Pd7b catalysts to produce
the corresponding -boryl carbonyl derivatives (Scheme 1).
catalysts showed activity for the boration of a,b-unsaturated esters and
ꢀ
aldehydes, and Fernandez and Guiry et al. reported the activity of
copper catalysts with axially chiral PeN ligands.9a,b Hoveyda et al. also
developed CueNHC catalyst for conjugate boration to attain con-
struction of boron-substituted quaternary carbons in high enantiose-
b
lectivity.10 Mazet et al. also attained copper catalyzed
b
-boration of
disubstituted cyclic enones with excellent ees.11 Kanai and Shibasaki
demonstrated enantioselective conjugate boration toward -di-
b,b-
b,b
substituted enones with chiral secondary diamineecopper catalyst to
attain 99% ee.12 The copper catalyzed conjugate boration was applied
to substrates of a,b
-unsaturated sulfones.13
In 2009, Hoveyda et al. developed excellent non-asymmetric
metal-free chiral NHC catalysis for conjugate boration of cyclic and
acyclic enones.14 Then they also attained asymmetric version of the
metal-free catalysis.15 In 2010, Gulyas and Fernandez succeeded
metal-free catalytic boration with chiral phosphines as organo-
ꢀ
ꢀ
Scheme 1. Asymmetric catalytic b-boration of a,b-unsaturated carbonyl compounds.
catalysts to attain 90% ee,16 and Bo, Gulyas, and Fernandez found
activation of the boration with Brønsted bases and alcohols.17 Thus,
attention has been focused on metal-free organocatalysts for the
conjugate boration.
ꢀ
ꢀ
* Corresponding author. Tel./fax: þ81 52 789 3335; e-mail address: hnishi@ap-
chem.nagoya-u.ac.jp (H. Nishiyama).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.086

3552
K. Toribatake et al. / Tetrahedron 69 (2013) 3551e3560
ꢀ
ꢀ
In 2011, Whiting, Gulyas, and Fernandez reported copper-
catalyzed boration of -unsaturated imines leading to synthesis
of
-aminoalcohols.18 In 2011, Santos et al. reported sp2esp3 diboron
methanol, the reaction with Rh(Phebox) directly produces rhodium
enolate species giving -boryl compounds after hydrolysis. Thus,
Rh(Phebox) catalysts include important aspect from the view points
a,b
b
g
reagent applied to copper catalyzed conjugate boration.19 In 2012,
Zhao, Marder, and Lin reported DFT studies on platinumediimine
complex catalyzing conjugate boration.20 Thus catalytic conjugate
boration has been extensively studied as potent methods of growing
interest for organic synthesis. It is also of importance that the cor-
responding borated compounds can readily be converted into opti-
cally active secondary alcohols by oxidation.
of organic reaction. We here wish to report the efficient asymmetric
b
-boration of a,b-unsaturated compounds with our rhodium cata-
lysts and to show scope and limitations.22
2. Results and discussion
2.1. Asymmetric boration of cinnamates
We have so far demonstrated highly enantioselective conjugate
reductions using rhodium[bis(oxazolinyl)phenyl] catalysts, Rh(Phe-
box) in the presence of hydrosilanes.21 Previously, we have pre-
We examined the boration of ethyl (E)-cinnamate 2a (0.5 mmol)
with bis(pinacolato)diboron (B2pin2) (1.2 equiv) and Rh(Phebox) 1
(1.0 mol %) in a toluene solution (Table 1). The boration at 60 ꢀC
liminarily reported an asymmetric
b-boration of a,b-unsaturated
carbonyl compounds promoted by Rh(Phebox).22 The reaction is the
first example of chiral rhodium-catalyzed boration with high enan-
tioselectivity. Comparing to the boration with copper or nickel cat-
alysts,7,8 which are accelerated by addition of protic solvent, such as
with the catalyst 1a formed
b-borated dihydrocinnamate 3a in
a low yield (entry 1). The boration at 80 ꢀC gave 3a in 64% with 94%
ee (entry 2). Furthermore, addition of NaOt-Bu (5 mol %) acceler-
ated the boration to improve the yield up to 92% with 93% ee even
Table 1
Asymmetric b
-boration of cinnamates with chiral Rh(Phebox) catalystsa
Entry
2
Cat.
Additive
Temp (ꢀC)
Time (h)
Yield of 3 (%)
ee of 4 (%)
1
2
3
4
5
6
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2c
2c
2d
2d
2e
2e
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1c
1d
1a
1b
1a
1b
1a
1b
1a
1b
d
60
80
60
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
12
12
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3c
3c
3d
3d
3e
3e
Trace
64
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
4c
4c
4d
4d
4e
4e
d
d
94
93
NaOt-Bu
NaOt-Bu
KOt-Bu
NaOMe
K2CO3
2.0
0.5
0.5
1.0
2.5
1.5
0.5
0.5
0.5
0.5
1.0
1.0
0.5
0.5
0.5
0.5
0.5
0.5
92
92 (84)b
85
93 (95)b
95
90
83
82
86
86
70
58
80
87
74
78
73
82
89
83
93
94
95
97
91
58
73
92
95
92
92
88
83
91
90
7c
8c
9
Cs2CO3
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
10d
11
12
13
14
15
16
17
18
19
20
a
The ester 2 (0.50 mmol), cat. 1 (0.005 mmol, 1.0 mol %), diboron (0.60 mmol), additive (0.025 mmol), toluene (1.0 mL).
Ref. 22.
Additive (0.05 mmol).
b
c
d
The ester (1.0 mmol), cat. 1 (0.001 mmol, 0.10 mol %), NaOt-Bu (0.005 mmol), diboron (1.2 mmol), toluene (5.0 mL).

K. Toribatake et al. / Tetrahedron 69 (2013) 3551e3560
3553
at 60 ꢀC, and the reaction at 80 ꢀC also gave 93% ee (entries 3 and 4).
The enantioselectivity was measured after oxidative conversion of
the product to the corresponding b-hydroxy dihydrocinnamate 4a.
Table 2
Asymmetric
b
-boration of
a
,b
-unsaturated esters with chiral Rh(Phebox) catalystsa
__________________________________________________________
Other bases as activating agents, such as KOt-Bu, NaOMe, K2CO3,
and Cs2CO3 were examined at 80 ꢀC to show almost similar results
in yields and ees (entries 5e8). Thus, the reaction was not strongly
affected by bases. Secondary butyl catalyst 1b resulted in 97% ee
(entry 9). It is noteworthy that the catalyst charge of 0.1 mol % could
promote the reaction in 86% and the ee of 91% (entry 10). Benzyl
catalyst 1c and phenyl catalyst 1d afforded the middle range of ees
(entries 11 and 12). The reaction of methyl ester 2b resulted
92e95% ees with the catalysts 1a and 1b, respectively (entries 13
and 14). The ees of 4b were almost the same as those with the ethyl
ester 4a. Isopropyl and benzyl esters (2c and 2e) gave high ees
around 90%, respectively (entries 15, 16, 19, and 20). Bulky tert-
butyl ester 2d decreased ees to 83e88 % (entries 17 and 18).
We examined sequential method of the boration and oxidation
Substrate
Product
in order to obtain the optically active b-hydroxy dihydrocinnamate
4a. After the catalytic boration, the solvent was removed under
reduced pressure. Then, water, THF and sodium peroxoborate were
added into the mixture, which was stirred at room temperature to
give 4a in good total yields and ee up to 95% (Scheme 2).
Scheme 2. Sequential procedure to optically active b-hydroxy dihydrocinnamates.
2.2. Substrate scope and limitations
Other substrates of a,b-unsaturated esters were next examined
with the catalyst 1a and 1b under the conditions similar to those of
entries 4 and 9 in Table 1 (Table 2). Substituted ethyl cinnamates
2fel were subjected to the boration giving higher ees in the range
of 92 up to 97% with 1b. The substrate with an electron-
withdrawing group 2h (p-CF3) decreased the yield to 75%.23 1-
and 2-Naphthyl acrylates 2m and 2n were also borated in 69% and
62% yields, respectively, with good to excellent ees. (Z)-Cinnamate
Z-2a was also readily borated to give adduct with the same absolute
configuration S in 93% ee. It was thought that quick isomerization
from Z-ester to E-ester occurred. On the basis of 1H NMR experi-
ment, the isomerization was confirmed in 50% within ca. 1 min at
80 ꢀC; Z-2a (0.25 mmol), toluene-d8 (0.5 mL), 1b (1 mol %), B2pin2
(0.3 mmol), NaOt-Bu (5 mol %), in an NMR tube; without NaOt-Bu,
the isomerization took place in ca. 30% for 5 min at 80 ꢀC. Alkyl
substituted acrylate 2o was smoothly borated to give the adduct 3o
in 90% yield and 86e90% ee. It is interesting in that the Z-isomer of
2o gave the reverse absolute configuration in 62% ee. The isomer-
ization of Z to E of 2o may be slow. Benzyl crotonate 2p was also
converted to the boryl ester 3p in 82e84% ee.
The catalytic boration of several a,b-unsaturated ketones was
examined (Table 3). Comparing to the boration of the esters, the
unsaturated ketones 5aef were borated in moderate yields
(64e89%) at 80 ꢀC for 2 h with 1 mol % of the catalyst. The enan-
tioselectivity were up to 85%. The reaction of phenyl propenyl ke-
tone 5f resulted in a low ee, 12%.
continued on next page

3554
K. Toribatake et al. / Tetrahedron 69 (2013) 3551e3560
Table 2 (continued)
Table 4
Asymmetric b-boration of a,b
-unsaturated amides with chiral Rh(Phebox) catalystsa
__________________________________________________________
Substrate Product
__________________________________________________________
a
The ester 2 (0.50 mmol), cat. 1 (0.005 mmol, 1.0 mol%), diboron (0.60
mmol), NaOt-Bu (0.025 mmol), toluene (1.0 mL). 80 °C, 0.5 h. Ees were
determined by HPLC with chiral column of the corresponding β-hydroxy
esters after oxidation of the borated product with NaBO3•(H2O)4 in THF-H2O.
For 2g, 3.0 mol% of 1b was used.
Table 3
Asymmetric
b-boration of a,b-unsaturated ketones with chiral Rh(Phebox)
catalystsa
__________________________________________________________
Substrate Product
__________________________________________________________
a
The amide 7 (0.50 mmol), cat. 1 (0.005 mmol, 1.0 mol%), diboron (0.60
mmol), NaOt-Bu (0.025 mmol), toluene (1.0 mL). 80 °C, 0.5 h. Ees were
determined by HPLC with chiral column of the corresponding -hydroxy
β
amides after oxidation of the borated product with NaBO3• (H2O)4 in THF–
H2O.
boration of N-substituted or N,N-disubstituted amides, only Yun et al.
reported one example for 7awith copper/chiral phosphine catalyst to
give 97% ee.8c As for the N-methoxy amide substrates, Hoveyda et al.
reported ees up to 90% with NHC organocatalyst.15
In order to expand scope of substrates, we examined several
functionalized compounds. However, the following a cyclic lactone,
b,b-disubstituted acrylate, cyclic enone, and N-methoxy cinnamate
did not react under the standard condition to be recovered.
__________________________________________________________
a
The ketone 5 (0.50 mmol), cat. 1 (0.005 mmol, 1.0 mol%), diboron
(0.60 mmol), NaOt-Bu (0.025 mmol), toluene (1.0 mL). 80 °C, 2.0 h. Ees
β
were determined by HPLC with chiral column of the corresponding
-
2.3. Hypothetical catalytic cycle and stereoselection
hydroxy ketones after oxidation of the borated product with NaBO3•(H2O)4 in
THF- H2O.
In order to investigate the boration mechanism, a reaction of
Rh(Phebox-ip) 1a and B2pin2 (1.2 equiv) in a NMR tube in a toluene-
d8 solution was carried at 80 ꢀC, in the presence and the absence of
NaOt-Bu, respectively. However, the corresponding boryl Rh(Phe-
Next, the catalytic boration of N,N-disubstituted a,b-unsaturated
amides 7 were examined (Table 4). The boration of the cinnamoyl
amides 7aec took place smoothly at 80 ꢀC to give the borated prod-
ucts 8aec in good yields with high ees up to 97%. Crotonoyl amide 7d
was also resulted in a good ee of 93%, which was better than that of
the corresponding ester 2p. In terms of the catalytic asymmetric
box-ip) species was not clearly confirmed. We think that the
s-
metathesis of BeB bond and RheOAc bond occurs at the initial
stage to form RheB bond. The addition of tert-butoxide anion can
accelerate the exchange reaction. Although the evidence is still

K. Toribatake et al. / Tetrahedron 69 (2013) 3551e3560
3555
lacked, we propose a possible catalytic cycle (Scheme 3). The
Rheboryl species (i) coordinates unsaturated carbonyl forming (ii),
steric repulsion between the substituent on the oxazoline skele-
ton and substrate.
followed by boryl-insertion forming a Rheenolate (iii), then the
s-
metathesis to regenerate the active Rheboryl species (i) producing
3. Conclusions
the b-boryl-boryl-O-enolate (iv).
We have found that Rh(Phebox) complexes exhibit catalytic
Rh = (Phebox)Rh(OAc)
B = Bpin
activity for asymmetric boration of a,b-unsaturated esters, ketones,
and amides to attain high enantioselectivities up to 97%. As one-pot
procedure, the boration mixture was subjected into oxidation with
OAc
Rh
B–B
t-BuO-
– B-OAc or B-Ot-Bu
peroxoborate to produce the corresponding optically active b-hy-
droxy dihydrocinnamates in high yields and high enantiose-
lectivity. Steric course of the boration providing the corresponding
absolute configuration was also proposed.
B
B
Rh
B
O
O
4. Experimental section
4.1. General information
iv
B–B
i
1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on
a Varian Mercury 300 spectrometer. 1H and 13C chemical shifts
B
Rh
B
Rh
were reported in
d units, in parts per million relative to the singlet
O
O
at 7.26 ppm and the triplet at 77.0 for CDCl3, respectively. Infrared
spectra were recorded on a JASCO FR/IR-230 spectrometer. Optical
rotation was measured on a JASCO P-1020NS polarimeter. HRMS
(FAB) was measured on double-focusing magnetic sector mass
spectrometer, JEOL JMS-700 at Chemical Instrumentation Facility of
Nagoya University. Rh(Phebox-R) complexes 1 were prepared by
our method.21 B2pin2 was purchased from Allychem Co. Ltd. (China)
and was purified by crystallization from pentane according to the
reported procedure.24
iii
ii
Scheme 3. Plausible catalytic cycle.
We also propose hypothetical transition-state structures
(Fig. 1). Considering the absolute configuration of the borylated
product E, the boryl group should attack the si-face of the cinna-
mate substrate. The structure A with si-face attack is most likely to
form the major enantiomer E rather than re-face attack on the
structure B. In the case of equatorial boryl structures C and D,
although C can produce the major isomer E, both C and D cause
4.2. Typical procedure for asymmetric boration of (E)-ethyl
cinnamate 2a and oxidation (Table 1, entry 9)
Rh(Phebox-sb) 1b (2.8 mg, 0.0050 mmol), bis(pinacolato)-
diboron (140 mg, 0.55 mmol), and NaOt-Bu (2.4 mg, 0.025 mmol)
were placed in a flask with a stirring bar. Under an argon atmosphere,
(E)-ethyl cinnamate 2a (88.1 mg, 0.50 mmol) and toluene (1.0 mL)
were added. The mixture was stirred at 80 ꢀC for 0.5 h. At room
temperature, the mixture was directly charged to a silica-gel column
with an eluant of hexane/ethyl acetate to give the borylated product
3a in 86% yield (131 mg, 0.43 mmol). A part of the product (ca.
0.2 mmol) was subjected to the oxidation with sodium peroxoborate
(5 equiv) in THF (1 mL) and H2O (1 mL) at room temperature for ca.
3 h to give the corresponding alcohol 4a. The enantioselectivity was
determined by chiral chromatography to give 97% ee.
For the one-pot reaction, bis(pinacolato)diboron (152 mg,
0.60 mmol) was used, and after the boration the solvent was re-
moved under the reduced pressure. To the residue, water (1.0 mL),
THF (1.0 mL), and NaBO3$(H2O)4 (384 mg, 2.5 mmol) were added.
The mixture was stirred at room temperature for 1 h, and was
extracted with ethyl acetate. The crude product was purified by
silica-gel column chromatography to give the corresponding alco-
hol 4a in 71% yield (69.2 mg, 0.357 mmol) with 95% ee.
4.2.1. (S)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-
phenylpropanoate 3a. Colorless oil. IR (film):
n 2978, 1731, 1371,
1323, 1141, 847, 701 cmꢁ1; 1H NMR: dH 1.18 (s, 6H),1.23 (s, 6H),1.23 (t,
J 7.2 Hz, 3H), 2.62e2.77 (m, 2H), 2.89 (dd, J 15.3, 9.6 Hz, 1H), 4.11 (m,
2H), 7.11e7.31 (m, 5H) ppm; 13C NMR: dC 14.4, 24.6, 24.7, 28.2 (CB,
broad), 37.4, 60.4, 83.5, 125.4, 128.0, 128.2, 141.1, 173.0; HRMS (FAB):
[Mꢂþ] m/z, found: 304.1840; calcd (C17H25O4B): 304.1849; ½a 2D7
þ20.7
ꢃ
(c 1.07, CHCl3), corresponding to 93% ee of 4a from (Z)-cinnamate.
4.2.2. (S)-Ethyl 3-hydroxy-3-phenylpropanoate 4a. Colorless oil. IR
Fig. 1. Proposed transition-state model for asymmetric boration.
(film): n
3471 (broad), 2982, 1730, 1195, 1037, 760 cmꢁ1; 1H NMR: dH

3556
K. Toribatake et al. / Tetrahedron 69 (2013) 3551e3560
1.27 (t, J 7.2 Hz, 3H), 2.88 (m, 2H), 3.30 (d, J 3.3 Hz, 1H), 4.19 (q, J
7.2 Hz, 2H), 5.14 (m, 1H), 7.22e7.42 (m, 5H) ppm; 13C NMR: dC 14.3,
43.4, 60.9, 70.3, 125.5, 127.6, 128.3, 142.2, 172.1. Chromatography:
DAICEL CHIRALCEL OD-H, hexane/2-propanol (90:10, 0.5 mL/min),
retention time: 15.2 min (major), 18.3 min (minor), 97% ee (S);
HRMS (FAB): [MþHþ] m/z, found: 195.1029; calcd (C11H15O3):
70.5, 81.7, 125.7, 127.6, 128.4, 142.5, 171.7. Chromatography: DAICEL
CHIRALPAK AS-H, hexane/2-propanol (99:1, 0.5 mL/min), retention
time: 20.3 min (minor), 21.1 min (major), 88% ee. HRMS (FAB):
[MþHþ] m/z, found: 223.1337; calcd (C13H19O3): 223.1334; ½a 2D4
ꢃ
ꢁ37.7 (c 1.2, CHCl3), 85% ee in Scheme 3, determined by chiral LC;
lit.,28
½
a 2D3
ꢃ
ꢁ10.5 (c 2.4, CHCl3) for S, 42% ee.
195.1021; ½a 2D6
ꢁ46.5 (c 1.04, CHCl3), 97% ee determined by chiral
ꢃ
LC; from (Z)-cinnamate: ½a D25
ꢃ
ꢁ43.6 (c 1.0, CHCl3), 93% ee de-
a 2D8
ꢁ45.8 (c 0.25, CHCl3), 90% ee (S);
4.2.9. (S)-Benzyl 3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
termined by chiral LC; lit.,8a
½
ꢃ
2-yl)propanoate 3e. Colorless oil. IR (film):
1734 cmꢁ1; 1H NMR: dH
n
lit.,25
[a
]
D ꢁ52 (c 1, CHCl3).
1.15 (s, 6H),1.20 (s, 6H), 2.70e3.03 (m, 3H), 5.05 (d, J 12.3 Hz,1H), 5.13
(d, J 12.3 Hz, 1H), 7.10e7.40 (m, 10H) ppm; 13C NMR: dC 25.0, 25.1,
25.7, 37.8, 66.5, 83.9, 125.9, 128.2, 128.3, 128.4, 128.6, 128.7, 136.2,
142.3, 173.2; C[B] was not detected; HRMS (FAB): [MþHþ] m/z,
4.2.3. (S)-Methyl 3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)propanoate 3b. Colorless oil. IR (film):
n 2978, 1737, 1371, 1323,
1141, 846, 701 cmꢁ1; 1H NMR: dH 1.18 (s, 6H), 1.23 (s, 6H), 2.63e2.80
(m, 2H), 2.90 (m, 1H), 3.66 (s, 3H), 7.13e7.30 (m, 5H) ppm; 13C NMR:
dC 24.6, 24.7, 25.2, 37.2, 51.6, 83.5, 125.5, 127.9, 128.3, 141.0, 173.4; C[B]
was not detected; HRMS (FAB): [Mꢂþ] m/z, found: 290.1701; calcd
found: 367.2072; calcd (C22H27O4B): 367.2081. ½a D26
þ19.7 (c 1.01,
ꢃ
CHCl3), corresponding to 91% ee.
4.2.10. (S)-Benzyl 3-hydroxy-3-phenylpropanoate 4e. Colorless oil.
IR (film):
3464, 1732, 1158 cmꢁ1; 1H NMR: dH 2.70e2.90 (m, 2H),
(C16H23O4B): 290.1689; ½a D16
ꢃ
þ18.2 (c 1.25, CHCl3), 95% ee of the
n
corresponding alcohol.
3.19 (s, 1H), 5.18 (m, 2H), 7.20e7.50 (m, 10H) ppm; 13C NMR: dC 43.4,
66.7, 70.3, 125.5, 127.6, 128.2, 128.4, 131.1, 135.2, 142.1, 154.9, 171.8.
Chromatography: DAICEL CHIRALCEL OD-H, hexane/2-propanol
(90:10, 0.5 mL/min), retention time: 21.6 min (major), 26.5 min
(minor), 91% ee; HRMS (FAB): [MþHþ] m/z, found: 279.0991; calcd
4.2.4. (S)-Methyl 3-hydroxy-3-phenylpropanoate 4b. Colorless oil. IR
(film):
3456, 1730,1438,1200, 762, 701 cmꢁ1; 1H NMR: dH 2.67e2.81
n
(m, 2H), 3.21 (br, 1H), 3.73 (s, 3H), 5.15 (m, 1H), 7.26e7.40 (m, 5H)
ppm; 13C NMR: dC 43.2, 52.0, 70.3, 125.5, 127.7, 128.4, 142.2, 172.4.
Chromatography: DAICEL CHIRALCEL OD-H, hexane/2-propanol
(90:10, 0.5 mL/min), retention time: 23.0 min (major), 36.4 min
(minor), 95% ee (S); HRMS (FAB): [MþNaþ] m/z, found: 203.0681;
(C16H16O3Na): 279.0997; ½a D26
ꢃ
ꢁ34.82 (c 1.12, CHCl3), 91% ee; lit.,29
½
a 2D5
ꢃ
þ28.6 (c 1.8, CH2Cl2) for R, 99% ee.
4.2.11. (S)-Ethyl 3-(4-methoxyphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-
calcd (C10H12O3Na): 203.0684; ½a D16
ꢃ
ꢁ52.9 (c 1.00, CHCl3), 95% ee
dioxaborolan-2-yl)propanoate 3f. Colorless oil. IR (film): n 2981,
determined by chiral LC; lit.,26
[
a
]
rt ꢁ51.3 (c 1.3, CHCl3), 93% ee for S.
1731,1369,1249,1033, 840 cmꢁ1; 1H NMR: dH 1.18 (s, 6H),1.23 (s, 6H),
1.23 (t, J 7.2 Hz, 3H), 2,58e2.73 (m, 2H), 2.80e2.90 (m, 1H), 3.77 (s,
3H), 4.10 (m, 2H), 6.81 (m, 2H), 7.14 (m, 2H) ppm; 13C NMR: dC 14.5,
24.7, 24.8, 37.8, 55.2, 60.4, 83.4, 113.7, 128.9, 133.1, 157.3, 173.1; C[B]
was not observed; HRMS (FAB): [Mꢂþ] m/z, found: 334.1943; calcd
D
4.2.5. (S)-Isopropyl 3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxabo-
rolan-2-yl)propanoate 3c. Colorless oil. IR (film): 2979, 1725, 1371,
n
1139, 970, 768, 706 cmꢁ1; 1H NMR: dH 1.18 (s, 6H), 1.19 (d, J 6.3 Hz, 6H),
1.28 (s, 6H), 2.62 (dd, J 5.7, 15.3 Hz, 1H), 2.73 (dd, J 5.7, 9.6 Hz, 1H), 2.85
(dd, J 9.6, 15.3 Hz, 1H), 4.98 (m, 1H), 7.15e7.30 (m, 5H) ppm; 13C NMR:
dC 22.2, 24.8, 24.9, 67.8, 83.6, 125.5, 128.2, 128.4, 141.3, 172.8; C[B] was
not detected; HRMS (FAB): [MþHþ] m/z, found: 319.2085; calcd
(C18H27O5B): 334.1955; ½a D26
þ31.5 (c 1.0, CHCl3), 94% ee of the cor-
ꢃ
responding alcohol. (S)-Ethyl 3-hydroxy-3-(4-methoxyphenyl)prop-
anoate: colorless oil. IR (film):
n
3475 (broad), 2980, 1728, 1610, 1511,
1248, 1173, 1032, 838 cmꢁ1
;
1H NMR: dH 1.26 (t, J 7.2 Hz, 3H),
(C18H28O4B): 319.2084; ½a D24
ꢃ
þ18.2 (c 1.04, CHCl3), 92% ee of the
2.60e2.80 (m, 2H), 3.80 (s, 3H), 4.17 (q, J 7.2 Hz, 2H), 5.08 (m,1H), 6.87
(m, 2H), 7.28 (m, 2H); 13C NMR: dC 14.3, 42.4, 55.3, 60.8, 69.9, 113.7,
126.7, 134.5, 158.8, 172.0. Chromatography: DAICEL CHIRALPAK AS-H,
hexane/2-propanol (95:5, 1.0 mL/min), retention time: 14.7 min
(minor), 18.4 min (major), 94% ee; HRMS (FAB): [MþNaþ] m/z, found:
corresponding alcohol.
4.2.6. (S)-Isopropyl 3-hydroxy-3-phenylpropanoate 4c. Colorless oil.
IR (film):
3060 (broad), 1729, 1107 cmꢁ1 1H NMR: dH 1.24 (d, J
n
;
6.0 Hz, 3H), 1.25 (d, J 6.3 Hz, 3H), 2.62-2.80 (m, 2H), 3.40 (br, 1H),
5.06 (m, 1H, CH(CH3)2), 5.12 (m, 1H, CHOH), 7.23e7.43 (m, 5H) ppm;
13C NMR: dC 22.3, 44.0, 68.8, 70.1, 125.9, 127.9, 128.7, 142.6, 172.0.
Chromatography: DAICEL CHIRALPAK AS-H, hexane/2-propanol
(97:3, 0.5 mL/min), retention time: 23.1 min (minor), 24.8 min
(major), 92% ee; absolute configuration was tentatively assigned to
S, as analogy of the ethyl ester; HRMS (FAB): [MþHþ] m/z, found:
247.0944; calcd (C12H16O4Na): 247.0946; ½a D26
ꢁ28.6 (c 1.0, CHCl3),
ꢃ
94% ee by chiral LC; lit.,30
[a]
D þ34 (c 2.0, CHCl3), 86% ee for R.
4.2.12. (S)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-
(p-tolyl)propanoate 3g. Colorless oil. IR (film):
1732 cmꢁ1 1H
n
;
NMR: dH 1.18e1.28 (m, 15H), 2.30 (s, 3H), 2.61e2.72 (m, 2H),
2.82e2.90 (m, 1H), 4.08e4.13 (m, 2H), 7.06 (d, J 8.4 Hz, 2H), 7.11 (d, J
7.8 Hz, 2H) ppm; 13C NMR: dC 14.5, 21.2, 24.7, 24.8, 25.2, 37.6, 60.4,
83.4, 127.9, 129.0, 134.8, 138.0, 173.1; HRMS (FAB): [Mꢂþ] m/z, found:
209.1179; calcd (C12H17O3): 209.1178; ½a D24
ꢃ
ꢁ39.6 (c 0.94, CHCl3),
þ39.4 (c 1.1, CHCl3) for R.
93% ee determined by chiral LC; lit.,27
½ ꢃ
a 2D0
318.2008; calcd (C18H27O4B): 318.2066; ½a D30
þ24.6 (c 1.20, CHCl3),
ꢃ
4.2.7. (S)-tert-Butyl 3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxabo-
rolan-2-yl)propanoate 3d. Colorless oil. IR (film): 2977, 1728, 1369,
96% ee of the corresponding alcohol. (S)-Ethyl 3-hydroxy-3-(p-tolyl)
n
propanoate: colorless oil. IR (film): n
3466, 1728 cmꢁ1; 1H NMR: dH
1140, 846, 701 cmꢁ1; 1H NMR: dH 1.17 (s, 6H), 1.23 (s, 6H), 1.41 (s, 9H),
2.60 (dd, J 5.5, 15.0 Hz, 1H), 2.68 (dd, J 5.5, 9.9 Hz, 1H), 2.80 (dd, J 9.9,
15.0 Hz, 1H), 7.05e7.30 (m, 5H) ppm; 13C NMR: dC 24.8, 24.9, 28.4,
38.6, 80.2, 83.5, 125.4, 128.2, 128.3,141.3, 172.6; C[B] was not detected;
HRMS (FAB): [MþHþ] m/z, found: 333.2244; calcd (C19H30O4B):
1.28 (t, J 7.2 Hz, 3H), 2.35 (s, 3H), 2.71e2.75 (m, 2H), 4.19 (q, J 7.2 Hz,
2H), 5.11 (dd, J 8.7, 3.9 Hz, 1H), 7.16 (d, J 8.4 Hz, 2H), 7.27 (d, J 8.4 Hz,
2H) ppm; 13C NMR: dC 14.4, 21.3, 43.4, 60.9, 70.2, 125.4, 129.0, 137.3,
139.3, 172.1; HRMS (FAB): [MþNaþ] m/z, found: 231.1002; calcd
(C12H16O3Na): 231.0997. Chromatography: DAICEL CHIRALPAK AS-
H, hexane/2-propanol (95:5, 1.0 mL/min), retention time: 10.7 min
333.2241; ½a 2D4
þ13.2 (c 1.59, CHCl3), 74% ee of the corresponding
ꢃ
alcohol.
(minor),11.3 min (major), 96% ee; ½a D29
ꢁ47.3 (c 1.00, CHCl3), 96% ee,
ꢃ
determined by chiral LC; lit.,31
½
a 2D5
ꢃ
ꢁ44.6 (c 1.2, CHCl3), 98% ee for S.
4.2.8. (S)-tert-Butyl 3-hydroxy-3-phenylpropanoate 4d. Colorless
oil. IR (film):
3443 (broad), 1730, 1368, 1149 cmꢁ1 1H NMR: dH
n
;
4.2.13. (S)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-
1.46 (s, 9H), 2.60e2.74 (m, 2H), 3.45 (d, J 3.3 Hz,1H), 5.09 (ddd, J 3.3,
(4-(trifluoromethyl)phenyl)propanoate 3h. White solids, mp
4.5, 7.8 Hz, 1H, OH), 7.26e7.42 (m, 5H) ppm; 13C NMR: dC 28.4, 44.5,
41e43 ꢀC. IR (film):
n ;
1731 cmꢁ1 1H NMR: dH 1.18e1.27 (m, 15H),

K. Toribatake et al. / Tetrahedron 69 (2013) 3551e3560
3557
2.63e2.91 (m, 3H), 4.08e4.14 (m, 2H), 7.32 (d, J 8.4 Hz, 2H), 7.51 (d, J
8.7 Hz, 2H) ppm; 13C NMR: dC 14.4, 24.7, 24.7, 25.2, 37.0, 60.6, 83.5,
83.8, 125.1, 125.1, 125.2, 125.2, 126.0, 128.2, 145.4, 173.6; HRMS
(FAB): [MþHþ] m/z, found: 373.1799; calcd (C18H24O4BF3):
14.2 min (major),18.0 min (minor), 97% ee;HRMS(FAB): [MþHþ] m/z,
found: 209.1183; calcd (C12H17O3): 209.1178; ½a D28
ꢁ44.3 (c 1.08,
ꢃ
CHCl3); lit.,32
½
a 2D0
ꢃ
ꢁ51 (c 1.00, CHCl3), 98% ee for S.
373.1798; ½a 2D8
ꢃ
þ10.8 (c 1.07, CHCl3), 92% ee of the corresponding
4.2.17. (S)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-
(o-tolyl)propanoate 3l. Colorless oil. IR (film):
1732 cmꢁ1 1H
alcohol. (S)-Ethyl 3-hydroxy-3-(4-(trifluoromethyl)phenyl)prop-
n
;
anoate: colorless oil. IR (film):
n
3430, 1729 cmꢁ1; 1H NMR: dH 1.28
NMR: dH 1.18e1.25 (m, 15 H), 2.37 (s, 3H), 2.60 (m, 1H), 2.82e2.98
(m, 2H), 4.05e4.17 (m, 2H), 7.02e7.17 (m, 4H) ppm; 13C NMR: dC
14.5, 20.2, 24.7, 24.8, 36.9, 60.4, 83.4, 125.3, 125.8, 127.4, 130.1, 135.9,
139.6, 173.2; C[B] was not observed; HRMS (FAB): [Mꢂþ] m/z, found:
(t, J 7.2 Hz, 3H), 2.73 (d, J 6.9 Hz, 2H), 4.20 (q, J 7.2 Hz, 2H), 5.19 (br,
1H), 7.51 (d, J 8.1 Hz, 2H), 7.62 (d, J 8.1 Hz, 2H) ppm; 13C NMR: dC
14.3, 43.2, 61.2, 69.7, 125.2, 125.3, 125.3, 125.4, 125.8, 146.1, 171.8;
HRMS (FAB): [Mꢂþ] m/z, found: 285.0714; calcd (C12H13O3F3):
285.0714. Chromatography: DAICEL CHIRALPAK AS-H, hexane/2-
propanol (98:2, 1.0 mL/min), retention time: 14.5 min (minor),
319.2071; calcd (C18H27O4B): 319.2081; ½a D27
þ20.3 (c 1.09, CHCl3),
ꢃ
92% ee of the corresponding alcohol. (S)-Ethyl 3-hydroxy-3-(o-tolyl)
propanoate: colorless oil. IR (film): n
1726 cmꢁ1; 1H NMR: dH 1.30 (t,
15.1 min (major), 92% ee; ½a D20
ꢃ
ꢁ37.8 (c 1.20, CHCl3), 92% ee; ab-
J 7.2 Hz, 3H), 2.36 (s, 3H), 2.63e2.76 (m, 2H), 3.19 (s, 1H), 4.21 (q, J
7.2 Hz, 2H), 5.36 (m, 1H), 7.13e7.27 (m, 3H), 7.50 (d, J 7.2 Hz, 1H)
ppm; 13C NMR: dC 14.4, 19.2, 42.2, 61.0, 67.0, 125.0, 126.2, 127.4,
130.2, 134.1, 140.2, 172.3. Chromatography: DAICEL CHIRALCEL OD-
H, hexane/2-propanol (90:10, 0.5 mL/min), retention time:
15.0 min (major), 22.0 min (minor), 92% ee; HRMS (FAB): [MþHþ]
solute configuration was tentatively assigned to S, as analogy of 4a.
4.2.14. (S)-Ethyl 3-(4-chlorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)propanoate 3i. Colorless oil. IR (film):
n
1724 cmꢁ1 1H NMR: dH 1.18e1.28 (m, 15H), 2.59e2.74 (m, 2H),
;
2.80e2.88 (m,1H), 4.06e4.15 (m, 2H), 7.14 (dt, J 9.0, 2.1 Hz, 2H), 7.22
(dt, J 9.0, 2.1 Hz, 2H) ppm; 13C NMR: dC 14.4, 24.7, 24.7, 25.2, 37.3,
60.5, 83.6, 128.3, 129.3, 139.7, 172.8; HRMS (FAB): [Mꢂþ] m/z, found:
m/z, found: 209.1183; calcd (C12H17O3): 209.1178; ½a D27
ꢁ58.6 (c
ꢃ
1.09, CHCl3); lit.,32
½
a 2D0
ꢃ
ꢁ87.9 (c 1.00, CHCl3), 92% ee for S.
338.1465; calcd (C17H24O4BCl): 338.1456; ½a D30
ꢃ
þ19.5 (c 1.12, CHCl3),
4.2.18. (S)-Ethyl 3-(naphthalen-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-
93% ee of the corresponding alcohol. (S)-Ethyl 3-(4-chlorophenyl)-3-
dioxaborolan-2-yl)propanoate 3m. White solids, mp 79e81 ꢀC. IR
hydroxypropanoate: colorless oil. IR (film):
n
3460, 1728 cmꢁ1
;
1H
(film): n ;
1727 cmꢁ1 1H NMR: dH 1.18e1.25 (m, 15H), 2.78 (m, 1H),
NMR: dH 1.27 (t, J 7.2 Hz, 3H), 2.70 (dd, J 7.8, 2.7 Hz, 2H), 4.19 (q, J
6.9 Hz, 2H), 5.11 (dd, J 7.5, 5.4 Hz, 1H), 7.32 (s, 4H) ppm; 13C NMR: dC
14.4, 43.3, 61.1, 69.6, 85.4, 126.9, 128.5, 140.7, 171.9; HRMS (FAB):
[MþNaþ] m/z, found: 251.0449; calcd (C11H13O3ClNa): 251.0451.
Chromatography: DAICEL CHIRALPAK AD-H, hexane/2-propanol
(95:5, 1.0 mL/min), retention time: 17.2 min (major), 18.9 min
3.04 (m,1H), 3.51 (dd, J 6.0, 9.6 Hz,1H), 4.04e4.20 (m, 2H), 7.38e7.50
(m, 4H), 7.68 (d, J 6.6 Hz,1H), 7.83 (d, J 7.5 Hz,1H), 8.17 (d, J 8.4 Hz,1H)
ppm; 13C NMR: dC 14.4, 24.7, 24.9, 37.3, 60.4, 83.7,123.9,125.2,125.4,
125.5, 126.3, 128.6, 131.7, 133.9, 137.8, 173.1; C[B] was not observed;
HRMS (FAB): [Mꢂþ] m/z, found: 354.2006; calcd (C21H27O4B):
354.2002; ½a 2D6
þ49.8 (c 1.0, CHCl3), 86% ee of the corresponding
ꢃ
(minor), 93% ee; ½a D32
ꢃ
ꢁ35.5 (c 1.18, CHCl3), 93% ee; lit.,31
½
a 2D5
ꢃ
ꢁ43.7
alcohol. (S)-Ethyl 3-hydroxy-3-(naphthalen-1-yl)propanoate: color-
(c 1.38, CHCl3), 99% ee for S.
less oil. IR (film): n
3488,1726 cmꢁ1; 1H NMR: dH 1.31 (t, J 7.2 Hz, 3H),
2.90 (m, 2H), 3.41 (br,1H), 4.24 (q, J 7.2 Hz, 2H), 5.93 (dd, J 3.0, 9.0 Hz,
1H), 7.47e7.57 (m, 3H), 7.71 (d, J 6.0 Hz,1H), 7.80 (d, J 7.8 Hz,1H), 7.88
(d, J 7.2 Hz,1H), 8.06 (d, J 8.1 Hz,1H) ppm; 13C NMR: dC 14.4, 42.3, 61.0,
67.3, 122.6, 122.8, 125.3, 125.4, 126.1, 128.1, 128.8, 129.7, 133.5, 137.7,
172.4. Chromatography: DAICEL CHIRALCEL OD-H, hexane/2-
propanol (90:10, 0.5 mL/min), retention time: 27.5 min (major),
33.6 min (minor), 86% ee; HRMS (FAB): [MþNaþ] m/z, found:
4.2.15. (S)-Ethyl 3-(4-(tert-butyl)phenyl)-3-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)propanoate 3j. Colorless oil. IR (film):
n 1732
cmꢁ1; 1H NMR: dH 1.19e1.29 (m, 24H), 2.61e2.73 (m, 2H), 2.82e2.90
(m, 1H), 4.08e4.14 (m, 2H), 7.13 (d, J 8.4 Hz, 2H), 7.26 (d, J 8.4 Hz, 2H)
ppm; 13C NMR: dC 14.5, 24.7, 24.8, 25.2, 31.5, 34.4, 37.7, 60.4, 83.4,
125.2, 127.6, 137.8, 148.0, 173.2; HRMS (FAB): [Mꢂþ] m/z, found:
360.2462; calcd (C21H33O4B): 360.2472; ½a D20
ꢃ
þ23.4 (c 0.85, CHCl3),
244.1087; calcd (C15H16O3): 244.1099; ½a D25
ꢁ64.8 (c 1.08, CHCl3);
ꢃ
97% ee of the corresponding alcohol. (S)-Ethyl 3-(4-(tert-butyl)phe-
absolute configuration was tentatively assigned to S, as analogy of
4a; see Ref. 33 for the corresponding methyl ester.
nyl)-3-hydroxypropanoate: colorless oil. IR (film):
n ;
3471, 1729 cmꢁ1
1H NMR: dH 1.25e1.33 (m, 12H), 2.67e2.83 (m, 2H), 3.17 (d, J 2.7 Hz,
1H), 4.19 (q, J 7.2 Hz, 2H), 5.12 (dd, J 8.1, 5.4 Hz, 1H), 7.28 (d, J 9.6 Hz,
2H), 7.39 (d, J 9.6 Hz, 2H) ppm; 13C NMR: dC 14.4, 31.5, 34.7, 43.3, 60.9,
70.1, 125.2, 125.3, 139.2, 150.5, 172.2; HRMS (FAB): [MþNaþ] m/z,
found: 273.1464; calcd (C15H23O3Na): 273.1467. Chromatography:
DAICEL CHIRALPAK AS-H, hexane/2-propanol (98:2, 1.0 mL/min), re-
4.2.19. (S)-Ethyl 3-(naphthalen-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)propanoate 3n. White solids, mp 48e50 ꢀC. IR
(film):
n
1725 cmꢁ1; 1H NMR: dH 1.18e1.28 (m, 15 H), 2.80 (m, 1H),
2.90e3.05 (m, 2H), 4.08e4.17 (m, 2H), 7.42e7.46 (m, 3H), 7.65 (s,
1H), 7.3e7.80 (m, 3H) ppm; 13C NMR: dC 14.5, 24.7, 24.8, 37.3, 60.5,
83.6, 124.9, 125.6, 125.9, 126.9, 127.3, 127.7, 131.7, 133.3, 138.7, 173.0;
C[B] was not observed; HRMS (FAB): [Mꢂþ] m/z, found: 354.2018;
tention time: 17.2 min (minor), 19.4 min (major), 97% ee; ½a D18
ꢁ34.3
ꢃ
(c 1.25, CHCl3), 97% ee.
calcd (C21H27O4B): 354.2002; ½a D27
þ23.4 (c 1.12, CHCl3), 84% ee of
ꢃ
4.2.16. (S)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-
(m-tolyl)propanoate 3k. Colorless oil. IR (film):
1732 cmꢁ1 1H
the corresponding alcohol. (S)-Ethyl 3-hydroxy-3-(naphthalen-2-yl)
n
;
propanoate: colorless oil. IR (film): n
1728 cmꢁ1; 1H NMR: dH 1.28 (t,
NMR: dH 1.26e1.19 (m, 15 H), 2.31 (s, 1H), 2.60e2.73 (m, 2H),
2.84e2.92 (m, 1H), 4.06e4.20 (m, 2H), 6.95e7.03 (m, 3H), 7.15 (t, J
7.5 Hz, 1H) ppm; 13C NMR: dC 14.5, 21.6, 24.68, 24.74, 37.5, 60.4, 83.5,
124.9, 126.2, 128.1, þ128.9, 137.7, 141.0, 173.1; C[B] was not observed;
J 7.2 Hz, 3H), 2.78e2.90 (m, 2H), 3.40 (s, 1H), 4.21 (q, J 7.2 Hz, 2H),
5.31 (m, 1H), 7.46e7.51 (m, 3H), 7.83e7.86 (m, 4H) ppm; 13C NMR:
dC 14.4, 43.4, 61.0, 70.4, 123.5, 124.3, 125.8, 126.0, 127.5, 127.8, 128.2,
132.8, 133.0, 139.6, 172.1. Chromatography: DAICEL CHIRALPAC AS-
H, hexane/2-propanol (99:1, 0.5 mL/min), retention time: 76.6 min
(minor), 83.3 min (major), 84% ee; HRMS (FAB): [MþNaþ] m/z,
HRMS (FAB): [Mꢂ
] m/z, found: 319.2095; calcd (C18H27O4B):
319.2081; ½a 2D6
þ26.7 (c 0.96, CHCl3), 97% ee of the corresponding
ꢃ
alcohol. (S)-Ethyl 3-hydroxy-3-(m-tolyl)propanoate: colorless oil. IR
found: 267.1001; calcd (C15H16O3): 267.0997; ½a D25
ꢁ16.3 (c 1.01,
ꢃ
(film):
n
3457, 1726, 1391 cmꢁ1; 1H NMR: dH 1.28 (t, J 7.2 Hz, 3H), 2.36
CHCl3); lit.,30
[a
]
D þ32 (c 1.8, CHCl3), 80% ee.
(s, 3H), 2.67e2.81(m, 2H), 4.19 (q, J 7.2Hz, 2H), 5.10 (m,1H), 7.09e7.27
(m, 4H), ppm; 13C NMR: dC 14.4, 21.6, 43.4, 60.9, 70.3, 122.5, 126.2,
128.2, 128.3, 138.0, 142.2, 172.1. Chromatography: DAICEL CHIRALCEL
OD-H, hexane/2-propanol (90:10, 0.5 mL/min), retention time:
4.2.20. (R)-Ethyl 5-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)pentanoate 3o. Colorless oil. IR (film): 2981, 2930, 1731, 1378,
1320, 1146 cmꢁ1; 1H NMR: dH 1.25 (t, J 7.2 Hz, 3H),1.26 (s, 6H),1.27 (s,
n

3558
K. Toribatake et al. / Tetrahedron 69 (2013) 3551e3560
6H), 1.40 (m, 1H), 1.67 (m, 1H), 1.79 (m, 1H), 2.45 (m, 2H), 2.65 (m,
2H), 4.12 (q, J 7.2 Hz, 2H), 7.12e7.20 (m, 3H), 7.22e7.30 (m, 2H) ppm;
13C NMR: dC 14.5, 20.0 (C-B), 24.9, 25.0, 32.8, 35.2, 35.9, 60.3, 83.2,
125.5, 128.1, 128.2, 142.3, 173.5; HRMS (FAB): [MþHþ] m/z, found:
(s, 3H), 5.10 (m, 1H), 6.87 (m, 2H), 7.27 (m, 2H) ppm; 13C NMR: dC
30.9, 52.0, 55.3, 69.5, 113.7, 126.7, 134.6, 158.8, 208.7. Chromatog-
raphy: DAICEL CHIRALPAK AD-H, hexane/2-propanol (95:5,
1.5 mL/min), retention time: 29.4 min (minor), 31.5 min (major),
333.2244; calcd (C19H30O4B): 333.2241; ½a D26
ꢃ
þ3.18 (c 1.03, CHCl3),
70% ee; HRMS (FAB): [Mꢂ
]
m/z, found: 194.0940; calcd
þ
86% ee of the corresponding alcohol. (R)-Ethyl 3-hydroxy-5-phenyl-
(C11H14O3): 194.0943; ½a D26
ꢃ
ꢁ33.9 (c 1.0, CHCl3), 70% ee; lit.,37
½ ꢃ
a 1D6
pentanoate: colorless oil. IR (film):
n
1726, 1186, 1034 cmꢁ1; 1H NMR:
ꢁ46.3 (c 0.4, CHCl3), 67% ee for R.
dH 1.28 (t, J 6.9 Hz, 3H), 1.72e1.92 (m, 2H), 2.40e2.56 (m, 2H), 2.70
(m, 1H), 2.80 (m, 1H), 3.12 (d, J 4.2 Hz, 1H), 4.02 (m, 1H), 4.17 (q, J
6.9 Hz, 2H), 7.16e7.21 (m, 3H), 7.24e7.29 (m, 2H) ppm; 13C NMR: dC
14.3, 31.9, 38.2, 41.4, 60.7, 67.2, 125.6, 128.1, 128.2, 141.5, 172.6.
Chromatography: DAICEL CHIRALCEL OD-H, hexane/2-propanol
(90:10, 1.0 mL/min), retention time: 24.7 min (minor), 29.3 min
(major), 86% ee; HRMS (FAB): [MþNaþ] m/z, found: 245.1148; calcd
4.2.24. (S)-1,3-Diphenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)propan-1-one 6c. Yellow oil. IR (film):
1683 cmꢁ1 1H NMR:
n
;
dH 1.18 (s, 6H), 1.27 (s, 6H), 2.81 (m, 1H), 3.43 (m, 1H), 3.58 (m, 1H),
7.18 (m, 1H), 7.25e7.35 (m, 4H), 7.40e7.50 (m, 2H), 7.54e7.60 (m,
1H), 7.98 (m, 1H) ppm; 13C NMR: dC 24.6, 24.7, 25.1, 43.4, 83.3, 125.4,
127.8, 128.2, 128.3, 128.3, 132.7, 136.5, 141.7, 199.2, C[B] was not
detected; HRMS (FAB): [MþHþ] m/z, found: 337.1973; calcd
(C13H18O3Na): 245.1154; ½a D26
ꢃ
þ0.58 (c 1.0, CHCl3), 86% ee de-
þ1.0 (c 1.0, CHCl3), 99% ee for R. (S)-
termined by chiral LC; lit.,34
½
a 2D5
ꢃ
(C21H25O3B): 337.1979; ½a D28
þ15.7 (c 1.01, CHCl3), 72% ee of the
ꢃ
Alcohol from Z-2o: colorless oil; ½a D18
ꢃ
ꢁ0.64 (c 1.03, CHCl3), 62% ee.
corresponding alcohol. (S)-3-Hydroxy-1,3-diphenylpropan-1-one:
colorless oil. IR (film):
n ;
3479, 1679 cmꢁ1 1H NMR: dH 3.39 (d, J
4.2.21. (R)-Benzyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)bu-
tanoate 3p. Colorless oil. IR (film):
2975, 1735, 1380, 1148 cmꢁ1; 1H
6.0 Hz, 2H), 3.66 (d, J 3.0 Hz, 1H, OH), 5.36 (dt, J 6.0, 3.0 Hz, 1H),
7.28e7.50 (m, 7H), 7.59 (tt, J 7.5,1.2 Hz,1H), 7.96 (dt, J 8.7, 1.5 Hz, 2H)
ppm; 13C NMR: dC 47.5, 70.0, 125.5, 127.4, 127.9, 128.3, 128.5, 133.4,
136.2, 142.6, 199.7; HRMS (FAB): [MþNaþ] m/z, found: 249.0891;
calcd (C15H14O2Na): 249.0883. Chromatography: DAICEL CHIR-
ALPAK AS-H, hexane/2-propanol (95:5,1.0 mL/min), retention time:
n
NMR: dH 1.02 (d, J 7.5 Hz, 3H), 1.22 (s, 6H), 1.23 (s, 6H), 1.42 (m, 1H),
2.42 (dd, J 6.6, 16.5 Hz, 1H), 2.51 (dd, J 7.8, 16.5 Hz, 1H), 5.08 (d, J
14.4 Hz, 1H), 5.13 (d, J 14.4 Hz,1H), 7.25e7.40 (m, 5H) ppm; 13C NMR:
dC 15.3, 24.8, 24.9, 33.8 (C-B), 37.8, 66.0, 83.1,127.8,127.9,128.2,136.0,
173.3; FAB-HRMS: [MþHþ] m/z, found: 305.1938; calcd (C17H26O4B):
17.2 min (major), 21.7 min (minor), 72% ee; ½a D28
ꢁ58.1 (c 1.03,
ꢃ
305.1927; ½a 2D7
ꢃ
ꢁ2.38 (c 0.99, CHCl3), 82% ee of the corresponding
CHCl3), 72% ee; lit.,8b
½
a 2D3
ꢃ
ꢁ107.3 (c 0.49, CHCl3), 80% ee for S.
alcohol. (R)-Benzyl 3-hydroxybutanoate: colorless oil. IR (film):
n
1729, 1382, 1290, 1172 cmꢁ1
;
1H NMR: dH 1.24 (d, J 6.3 Hz, 3H),
4.2.25. (S)-1-(4-Methoxyphenyl)-3-phenyl-3-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)propan-1-one 6d. Colorless oil. IR (film):
1671 cmꢁ1 1H NMR: dH 1.17 (s, 6H), 1.24 (s, 6H), 2.78 (dd, J 10.7,
2.44e2.59 (m, 2H), 2.98 (br, 1H), 4.22 (m, 1H), 5.16 (s, 2H), 7.33e7.40
(m, 5H) ppm; 13C NMR: dC 22.6, 42.9, 64.3, 66.5, 128.0, 128.2, 128.4,
135.3, 172.3. Chromatography: DAICEL CHIRALCEL OD-H, hexane/2-
propanol (98:2, 0.5 mL/min), retention time: 39.5 min (major),
56.1 min (minor), 82% ee; HRMS (FAB): [MþHþ] m/z, found:
n
;
5.4 Hz, 1H), 3.35e3.55 (m, 2H), 3.86 (s, 3H), 6.91 (dd, J 12.0,
3.0 Hz, 2H), 7.14e7.19 (m, 1H), 7.25e7.32 (m, 4H), 7.94 (dt, J 12.0,
2.1 Hz, 2H); 13C NMR: dC 14.3, 22.8, 24.7, 25.2, 43.1, 55.5, 83.2,
113.4, 125.3, 128.2, 128.3, 129.6, 130.1. 141.8, 163.0, 197.7; HRMS
(FAB): [MþHþ] m/z, found: 367.2096; calcd (C22H28O4B):
195.1017; calcd (C11H15O3): 195.1021; ½a D27
ꢁ26.0 (c 1.0, CHCl3), 82%
ꢃ
ee; lit.,35
[a]
D þ29.0 (c 1.0, CHCl3), 94% ee for S.
367.2081; ½a 1D5
þ10.3 (c 0.96, CHCl3), 62% ee of the corresponding
ꢃ
4.2.22. (S)-4-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)
butan-2-one 6a. Colorless oil. IR (film): 2981, 1711, 1365, 1321,
1145, 699 cmꢁ1 1H NMR: dH 1.17 (S, 6H), 1.23 (s, 6H), 2.15 (s, 3H),
alcohol. (S)-3-Hydroxy-1-(4-methoxyphenyl)-3-phenylpropan-1-
n
one: colorless oil. IR (film): n ;
3518, 1658 cmꢁ1 1H NMR: dH
;
3.31e3.38 (m, 2H), 3.82 (d, J 2.7 Hz, 1H), 3.88 (s, 3H), 5.31e5.35
(m, 1H), 6.93 (tt, J 8.7, 1.8 Hz, 2H), 7.28e7.46 (m, 5H) 7.93 (tt, J 9.0,
2.4 Hz, 2H) ppm; 13C NMR: dC 47.0, 55.6, 70.1, 113.7, 125.5, 127.4,
128.3, 129.3, 130.3, 142.7, 163.6, 198.3. Chromatography: DAICEL
CHIRALCEL OJ, hexane/2-propanol (90:10, 1.0 mL/min), retention
time: 53.8 min (minor), 60.7 min (major), 62% ee; HRMS (FAB):
[MþNaþ] m/z, found: 279.0992; calcd (C16H16O3Na): 27.0997;
2.64 (m, 1H), 2.84 (dd, J 5.1, 18.3 Hz,1H), 3.05 (dd, J 11.0, 18.3 Hz,1H),
7.10e7.30 (m, 5H) ppm; 13C NMR: dC 24.67, 24.69, 29.8, 47.6, 83.4,
125.3, 128.0, 128.3, 141.4, 207.9; C[B] was not observed; HRMS
(FAB): [MþHþ] m/z, found: 275.1818; calcd (C16H24O3B): 275.1822;
½
a 2D6
ꢃ
þ21.1 (c 1.0, CHCl3), 58% ee of the corresponding alcohol. (S)-4-
Hydroxy-4-phenylbutan-2-one: colorless oil. IR (film):
n 3452
(broad), 1707, 1362, 1059, 754, 697 cmꢁ1 1H NMR: dH 2.21 (s, 3H),
;
½
a 1D8
ꢃ
ꢁ41.78 (c 0.99, CHCl3), 62% ee; absolute configuration was
2.80e2.90 (m, 2H), 3.29 (br s, 1H), 5.16 (m, 1H), 7.20e7.40 (m, 5H)
ppm; 13C NMR: dC 30.9, 52.0, 69.8, 125.4, 127.5, 128.3, 142.4, 208.7.
Chromatography: DAICEL CHIRALPAK AS-H, hexane/2-propanol
(95:5, 1.5 mL/min), retention time: 10.8 min (minor), 12.6 min
(major), 58% ee; HRMS (FAB): [MþNaþ] m/z, found: 187.0742; calcd
tentatively assigned to S, as analogy of the corresponding alcohol
derived from 6c.
4.2.26. (S)-3-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
1-(4-(trifluoromethyl)phenyl)propan-1-one 6e. Colorless oil. IR (film):
(C10H12O2Na): 187.0735; ½a D26
ꢃ
ꢁ35.6 (c 1.0, CHCl3), 58% ee; lit.,36
n ;
1683 cmꢁ1 1H NMR: dH 1.17 (s, 6H), 1.27 (s, 6H), 2.80 (m, 1H),
½
a 2D0
ꢃ
ꢁ51.3 (c 1.0, CHCl3), 79% ee for S.
3.35e3.45 (m, 1H), 3.53e3.63 (m, 1H), 7.17 (m, 1H), 7.20e7.30 (m,
4H), 7.70 (d, J 8.0 Hz, 2H), 8.06 (d, J 8.0 Hz, 2H); 13C NMR: dC 24.6, 24.7,
25.1, 43.6, 83.4, 125.3, 125.4, 127.5, 128.1, 128.1, 128.4, 139.0, 141.2,
198.3, C[F] was not observed; HRMS (FAB): [MþHþ] m/z, found:
4.2.23. (S)-4-(4-Methoxyphenyl)-4-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)butan-2-one 6b. Colorless oil. IR (film):
n 2981,
1710, 1364, 1249, 1145, 833 cmꢁ1; 1H NMR: dH 1.29 (s, 6H), 1.35 (s,
6H), 2.25 (s, 3H), 2.70 (dd, J 5.4, 10.5 Hz, 1H), 2.92 (dd, J 5.4, 18.0 Hz,
1H), 3.11 (dd, J 10.5, 18.0 Hz, 1H), 3.89 (s, 3H), 6.92 (m, 2H), 7.24 (m,
2H) ppm; 13C NMR: dC 24.61, 24.63, 25.8 (broad, C[B]), 29.7, 47.6,
55.1, 83.2, 113.7, 128.8, 133.2, 157.2, 208.0; HRMS (FAB): [Mꢂþ] m/z,
405.1849; calcd (C22H25O3BF3): 405.1849; ½a D18
þ17.3 (c 1.05, CHCl3),
ꢃ
85% ee of the corresponding alcohol. (S)-3-Hydroxy-3-phenyl-1-(4-
(trifluoromethyl)phenyl)propan-1-one: colorless oil. IR (film): n 3500,
1707 cmꢁ1; 1H NMR: dH 3.31e3.50 (m, 3H), 5.38 (dd, J 9.0, 3.0 Hz,1H),
7.29e7.46 (m, 5H), 7.73 (d, J 8.7 Hz, 2H), 8.06 (d, J 8.1 Hz, 2H) ppm;
13C NMR: dC 47.9, 69.9, 125.5, 125.5, 125.6, 127.7, 128.3, 128.4, 138.9,
142.4, 198.5; HRMS (FAB): [MþNaþ] m/z, found: 317.0765; calcd
(C16H13OF3Na): 317.0765. Chromatography: DAICEL CHIRALCEL OJ-H,
hexane/2-propanol (95:5, 1.0 mL/min), retention time: 35.2 min
found: 304.1844; calcd (C17H25O4B): 304.1849; ½a D26
þ23.3 (c 1.0,
ꢃ
CHCl3), 70% ee of the corresponding alcohol. (S)-4-Hydroxy-4-(4-
methoxyphenyl)butan-2-one: colorless oil. IR (film):
(broad), 2929, 1707, 1513, 1249, 1173, 832 cmꢁ1 1H NMR: dH 2.20
(s, 3H), 2.78 (dd, J 3.6, 17.7 Hz, 1H), 2.89 (dd, J 9.0, 17.7 Hz, 1H), 3.80
n 3500
;
(minor), 37.0 min (major), 85% ee; ½a D21
ꢁ48.10 (c 1.04, CHCl3), 85%
ꢃ

K. Toribatake et al. / Tetrahedron 69 (2013) 3551e3560
3559
ee; absolute configuration was tentatively assigned to S, as analogy
of the corresponding alcohol derived from 6c.
ppm; 13C NMR: dC 37.3, 42.2, 70.7, 125.5, 126.9, 127.2, 128.0, 128.1,
129.7,142.7,142.9,172.0. Chromatography: DAICEL CHIRALCEL OD-H,
hexane/2-propanol (95:5, 0.5 mL/min), retention time: 48.1 min
(minor), 51.9 min (major), 95% ee; HRMS (FAB): [MþHþ] m/z, found:
4.2.27. (S)-1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)
butan-1-one 6f. Colorless oil. IR (film):
n
1683 cmꢁ1; 1H NMR: dH 1.17
256.1334; calcd (C16H18NO2): 256.1338; ½a D26
ꢁ20.0 (c 1.08, CHCl3);
ꢃ
(s, 6H) 1.23 (s, 6H), 2.15 (s, 3H), 2.62 (m, 1H), 2.82 (dd, J 10.8, 5.4 Hz,
1H), 3.03 (m, 1H), 7.11e7.28 (m, 5H); 13C NMR: dC 24.67, 24.69, 24.7,
29.7, 47.6, 83.4,125.3,128.0,128.3,141.4, 207.9; HRMS (FAB): [MþHþ]
absolute configurationwas tentatively assigned to S, as analogy of the
corresponding alcohol derived from 8a.
m/z, found: 275.1819; calcd (C16H23O3B): 275.1810. ½a D20
ꢃ
þ1.42 (c 1.0,
4.3.3. (S)-1-Morpholino-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-
CHCl3), 12% ee of the corresponding alcohol. (S)-3-Hydroxy-1-phe-
dioxaborolan-2-yl)propan-1-one 8c. White solids, mp 146e148 ꢀC.
nylbutan-1-one: colorless oil. IR (film):
n
3500,1707 cmꢁ1; 1H NMR: dH
IR (KBr): n
2976, 1634, 1437, 1358, 1231, 776, 705 cmꢁ1; 1H NMR: dH
1.31 (d, J 6.3 Hz, 3H), 2.99(br,1H), 3.00e3.21 (m, 2H), 4.41 (m,1H), 7.47
(tt, J 7.2, 2.1 Hz, 2H) 7.58 (tt, J 7.5, 1.5 Hz,1H) 7.95 (dt, J 8.4, 1.5 Hz, 2H)
ppm; 13C NMR: dC 22.6, 46.6, 64.0, 127.8, 128.5, 133.3, 136.4, 200.4;
HRMS (FAB): [MþNaþ] m/z, found: 187.0740; calcd (C10H12O2):
187.0735. Chromatography: DAICEL CHIRALCEL OD-H, hexane/2-
propanol (95:5, 1.0 mL/min), retention time: 12.6 min (minor),
1.17 (s, 6H), 1.20 (s, 6H), 2.67 (m, 1H), 2.75e2.90 (m, 2H), 3.40 (m,
2H), 3.50e3.70 (m, 6H), 7.17 (m, 2H), 7.20e7.30 (m, 3H) ppm; 13C
NMR: dC 24.77, 24.79, 37.5, 42.4, 45.9, 66.5, 66.8, 82.8, 125.2, 128.1,
128.2, 142.0, 171.8; HRMS (FAB): [Mꢂþ] m/z, found: 345.2115; calcd
(C19H28O4NB): 345.2111; ½a D18
þ27.5 (c 1.01, CHCl3), 91% ee of the
ꢃ
corresponding alcohol. (S)-3-Hydroxy-1-morpholino-3-phenyl-
13.7 min (major), 12% ee; ½a D20
ꢃ
þ7.63 (c 1.03, CHCl3), 12% ee.
propan-1-one: colorless oil. IR (film): n 3417, 2857, 1633, 1454, 1114,
702 cmꢁ1; 1H NMR: dH 2.64 (d, J 6.3 Hz, 2H), 3.35 (m, 2H), 3.48e3.73
(m, 6H), 4.51 (d, J 2.7 Hz, 1H), 5.17 (m, 1H), 7.20e7.42 (m, 5H) ppm;
13C NMR: dC 41.7, 41.8, 45.7, 66.3, 66.6, 70.3, 125.4, 127.3, 128.2,
142.6, 170.1. Chromatography: DAICEL CHIRALPAK AS-H, hexane/2-
propanol (90:10, 1.0 mL/min), retention time: 46.3 min (major),
65.9 min (minor), 91% ee; HRMS (FAB): [MþNaþ] m/z, found:
4.3. Typical procedure for asymmetric boration of cinnama-
mide 7b
Rh(Phebox-sb) 1b (2.8 mg, 0.0050 mmol), bis(pinacolato)
diboron (152 mg, 0.60 mmol, 1.2 equiv), NaOt-Bu (2.4 mg,
0.025 mmol) were placed in a flask with a stirring bar. Under an
argon atmosphere, the cinnamamide 7b (113 mg, 0.50 mmol) and
toluene (1.0 mL) were added. The mixture was stirred at 80 ꢀC for
0.5 h. At room temperature, the mixture was directly charged to
a silica-gel column with eluant of hexane/ethyl acetate to give the
borylated product 8b in 79% (144.3 mg, 0.395 mmol). The solution
of 8b (48.5 mg, 0.130 mmol) and NaBO3$(H2O)4 (100 mg,
0.65 mmol) in THF (1.0 mL) and H2O (1.0 mL) was stirred at room
temperature for 3 h. The mixture was extracted with ethyl acetate
(15 mLꢄ3). After concentration of the extract, the residue was
purified by silica-gel column chromatography with hexane/ethyl
258.1113; calcd (C13H17NO3Na): 258.1106; ½a D20
ꢁ71.3 (c 1.10,
ꢃ
CHCl3); absolute configuration was tentatively assigned to S, as
analogy of the corresponding alcohol derived from 8a.
4.3.4. (R)-N-Methyl-N-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)butanamide 8d. Colorless oil. IR (KBr):
n 2974,
1650, 1386, 1311, 1146, 861, 701 cmꢁ1; 1H NMR: dH 0.88 (d, J 7.2 Hz,
3H), 1.24 (br, 1H), 1.257 (s, 6H), 1.260 (s, 6H), 2.17 (br, 2H), 3.25 (s,
3H), 7.17 (m, 2H), 7.30e7.45 (m, 3H) ppm; 13C NMR: dC 15.3, 24.9,
25.2, 37.5, 38.5, 82.6, 127.1, 127.3, 129.4, 143.9, 173.2; HRMS (FAB):
[MþHþ] m/z, found: 304.2085; calcd (C17H27O3NB): 304.2084; ½a 2D1
ꢃ
acetate as eluant to give the corresponding
b-hydroxyamide
þ28.7 (c 1.2, CHCl3), 93% ee of the corresponding alcohol. (R)-3-
(31.6 mg, 0.124 mmol) in 93% yield; 95% ee by chiral LC.
Hydroxy-N-methyl-N-phenylbutanamide: Colorless oil. IR (film): n
3435, 2969, 1644, 1496, 1391, 1124, 701 cmꢁ1; 1H NMR: dH 1.07 (d, J
6.3 Hz, 3H), 2.09 (dd, J 9.0, 16.5 Hz, 1H), 2.22 (dd, J 3.0, 16.5 Hz, 1H),
3.28 (s, 3H), 4.11 (m, 1H), 4.38 (m, 1H, OH), 7.18 (m, 2H), 7.30e7.50
(m, 3H) ppm; 13C NMR: dC 22.4, 37.2, 41.9, 64.5, 127.0, 127.9, 129.7,
143.1, 172.5. Chromatography: DAICEL CHIRALPAK AS-H, hexane/2-
propanol (90:10, 0.5 mL/min), retention time: 34.7 min (major),
42.7 min (minor), 93% ee; HRMS (FAB): [MþNaþ] m/z, found:
4.3.1. (S)-N,N-Dimethyl-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)propanamide 8a. White solids, mp 108e109 ꢀC.
IR (KBr):
n ;
2978, 1642, 1361, 1139, cmꢁ1 1H NMR: dH 1.14 (s, 12H),
2.60 (m, 1H), 2.83 (m, 1H), 2.95 (m, 1H), 2.99 (s, 3H), 3.01 (s, 3H),
7.05e7.16 (m, 5H) ppm; 13C NMR: dC 24.8, 24.9, 30.8 (C-B), 36.1, 37.3,
38.2, 82.0, 124.8, 127.9, 128.1, 142.8, 174.4; HRMS (FAB): [Mꢂþ] m/z,
found: 303.2011; calcd (C17H26O3NB): 303.2009; ½a D27
ꢃ
þ38.4 (c 1.0,
216.0996; calcd (C11H15NO2Na): 216.1000; ½a D18
ꢁ4.6 (c 1.0, CHCl3);
ꢃ
CHCl3), 97% ee of the corresponding alcohol. (S)-3-Hydroxy-N,N-
absolute configuration was tentatively assigned to R.
dimethyl-3-phenylpropanamide: colorless oil. IR (film):
n 3413
(broad), 1623, 1406 cmꢁ1 1H NMR: dH 2.80e2.88 (m, 2H), 2.95 (s,
;
Acknowledgements
3H), 2.99 (s, 3H), 4.80 (s, 1H, OH), 5.14 (m, 1H, CHOH), 7.24e7.46 (m,
5H) ppm; 13C NMR: dC 35.3, 37.2, 42.0, 70.4, 125.5, 127.3, 128.2,
142.7, 171.9. Chromatography: DAICEL CHIRALCEL OD-H, hexane/2-
propanol (95:5, 0.5 mL/min), retention time: 44.0 min (major),
51.6 min (minor), 97% ee; HRMS (FAB): [MþHþ] m/z, found:
This research was partly supported by the Japan Society for the
Promotion of Science (No. 22245014). H.N. thanks Dr. Takushi Shiomi
and Mr. Takahiro Adachi for initial contributions of this study.
194.1175; calcd (C11H16NO2): 194.1181; ½a D26
ꢁ90.5 (c 1.07, CHCl3),
ꢃ
Supplementary data
a 24
97% ee; lit.,8c ½ ꢃD ꢁ87.9 (c 0.40, CHCl3), 96% ee for S.
1H and 13NMR spectra of selected products and the corre-
sponding alcohols and HPLC of the alcohols. Supplementary data
related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.02.086.
4.3.2. (S)-N-Methyl-N,3-diphenyl-3-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)propanamide 8b. Colorless oil. IR (KBr):
n 1651,
cmꢁ1; 1H NMR:dH 1.20 (s, 6H),1.22 (s, 6H), 2.45(m,1H), 2.60e2.66 (m,
2H), 3.27 (s, 3H), 7.08e7.37 (m, 10H) ppm; 13C NMR: dC 24.75, 24.80,
37.6, 38.6, 82.8, 125.0, 127.0, 127.5, 128.0, 128.1, 129.4, 142.0, 143.5,
173.0; HRMS (FAB): [Mꢂþ] m/z, found: 365.2171; calcd (C22H28O3NB):
References and notes
365.2162; ½a 2D6
þ34.8 (c 1.02, CHCl3), 95% ee of the corresponding
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