Felkin-Anh selectivity in Rh(bisoxazolinylphenyl)-catalyzed reductive aldol coupling reaction: asymmetric synthesis of stereotriads

Article abstract of DOI:10.1016/j.tet.2008.07.092

The catalytic reductive aldol coupling of 2-phenylpropionaldehyde and acrylate derivatives with rhodium-bisoxazolinyl catalysts resulted in high Felkin-Anh selectivity (β,γ-syn) up to 98% accompanied by α,β-anti diastereoselectivity and high enantiomeric excesses up to 99%.

Full text of DOI:10.1016/j.tet.2008.07.092

Tetrahedron 64 (2008) 9408–9412
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Felkin–Anh selectivity in Rh(bisoxazolinylphenyl)-catalyzed reductive aldol
coupling reaction: asymmetric synthesis of stereotriads
*
Toru Hashimoto, Jun-ichi Ito, 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:
Received 11 June 2008
Received in revised form 22 July 2008
Accepted 22 July 2008
Available online 26 July 2008
The catalytic reductive aldol coupling of 2-phenylpropionaldehyde and acrylate derivatives with rho-
dium-bisoxazolinyl catalysts resulted in high Felkin–Anh selectivity (
b,g-syn) up to 98% accompanied by
a,b-anti diastereoselectivity and high enantiomeric excesses up to 99%.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Rhodium
Asymmetric catalysis
Reductive aldol reaction
Felkin–Anh
Bisoxazoline
1. Introduction
synthesis of macrolides or other large naturally occurring
compounds.5
The asymmetric reductive aldol coupling reaction initiated by
hydride promoters has been recognized as a potent and versatile
We report here study on asymmetric synthesis of stereotriads
and b,g-stereoselectivity, Felkin–Anh or anti-Felkin–Anh, as sum-
method for construction of
a
,
b-stereogenic centers with
a
,b
-un-
marized in Scheme 2.
saturated carbonyl compounds such as enones or acrylates as
enolate precursors and aldehydes or imines as acceptors.1 For ex-
2. Results and discussion
ample, Morken reported high
coupling of methyl acrylate and
iridium-bisoxazolinylpyridine catalyst and Et2MeSiH.2 On the other
hand, we observed high -anti selectivity of up to 98% in the
a,
b
-syn selectivity of up to 90% in the
a
-benzyloxyacetoaldehyde with
The reductive coupling reaction of racemic 2-phenylpropanal
(5) (1.0 mmol) and tert-butyl acrylate (6) (2.0 equiv) with achiral
catalyst 1a (1 mol %) in the presence of (EtO)2MeSiH (2.2 equiv) was
carried out at 50 ꢀC for 30 min in a toluene solution (Table 1). The
reaction mixture was treated with KF (5 equiv) and TBAF to give the
desired b-hydroxyester 7 in 84% yield with 69% a,b-anti,syn selec-
tivity, i.e., selective formation of the Felkin–Anh product. The
product of the second-highest diastereomer ratio (dr), 21%, was
a,b
coupling of tert-butyl acrylate and benzaldehyde with rhodium-
bisoxazolinylphenyl catalyst and (EtO)2MeSiH.3 These reactions
have complementary stereoselectivity. Furthermore, Morken
extended the reaction to double stereodifferentiation with (R)-
a-benzyloxypropionaldehyde to observe
a,b-syn-Felkin–Anh selec-
tivity (i.e., -syn) (Scheme 1). Interestingly, no coupling was
b,g
presumed to be a,b-anti,anti-Felkin–Anh product on the basis of
observed by use of the corresponding (S)-aldehyde, which is thought
to be a mismatched acceptor under catalyst control. Recently, Kri-
catalyst control. The use of an optically active aldehyde (S)-5 (92%
ee) resulted in formation of the corresponding coupling product
(2R,3R,4S)-7 in 68% dr with 93% ee. Use of other silanes, such as
Me2PhSiH and MePh2SiH, gave slightly high stereoselectivities of 74
and 79% drs with 91 and 93% ees, respectively.
sche reported high anti-Felkin–Anh selectivity (
to 95% in the hydrogen-mediated coupling of methyl vinyl ketone
and
-aminoaldehydes with rhodium catalyst.4
Asymmetric construction of -stereotriads is an important
a,b-syn,b,g-anti) up
a
a,b,g
We considered that Felkin–Anh selectivity (b,g-syn) could be
and challenging subject for organic synthesis, especially for total
derived from differences in steric repulsion between Ph and Me
groups and the 1,3-diaxial interaction between Ph/H and Me/H, via
Zimmerman–Traxler type chair-like transition state of Rh-E(O)-
* Corresponding author. Fax: þ81 52 789 3209.
E-mail address: hnishi@apchem.nagoya-u.ac.jp (H. Nishiyama).
enolate, which gives rise to a,b
-anti diastereoselectivity (Fig. 1).6,7
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.092

T. Hashimoto et al. / Tetrahedron 64 (2008) 9408–9412
9409
Morken's catalysis
O
O
N
N
N
indane-pybox
[Ir(COE)2Cl] cat.
indane-pybox
Et2MeSiH
Me
Me
Me
β
H
+
α
γ
BnO
CO2Me
BnO
R
25 °C, 24 h
then H3O+
CO2Me
OH
O
50% yield
α β syn,Felkin-Anh (95%)
Scheme 1. Example for asymmetric synthesis of stereotriads by reductive aldol coupling reactions.
Next, we examined the reaction of the chiral catalyst 1b with
racemic aldehyde 5, which similarly provided the (2R,3R,4S)-anti-
Felkin–Anh product in a diastereomer ratio with 76% ee (Table 2).
Evidently, the (S)-aldehyde 5 was selectively captured to give (4S)-
with (S)-2-phenylpropanal in the presence of chiral catalyst 1b
(Scheme 3). The crotonate and the cinnamate provided high dia-
stereoselectivity (>98:2, >91:9) and enantioselectivity (98%, 97%)
for anti-Felkin–Anh products. The methacrylate 10 also resulted in
absolute configuration at the
g-carbon atom. When the chiral al-
high b,g-syn selectivity with high enantioselectivity of 91%.
dehyde (S)-5 (92% ee) was employed, high diastereomer ratio of
88% was obtained for anti-Felkin–Anh product, and the enantio-
meric excess was found to be 99%. It was thus clear that the (S,S)-
catalyst and (S)-aldehyde could make a matched pair. Me2PhSiH
and MePh2SiH gave almost similar yields and stereoselectivities
over 80% drs and 98% ees. On the other hand, when (R)-aldehyde
(95% ee) was employed as an acceptor, anti-Felkin–Anh decreased
to 20% and anti,anti-Felkin–Anh product was the main di-
astereomer in 71% ee.8,9
We believe that the catalyst-controlled reaction with the chiral
catalyst can preferably direct Si-face of the generated enolate spe-
cies i to the acceptor aldehyde rather than Re-face of the enolate ii
(Fig. 2). In addition, if the (R)-aldehyde is captured by the in-
termediate rhodium enolate, the sterically unfavorable transition
state iii forms anti,anti-Felkin–Anh product.
A single crystal of the corresponding sulfonamide-ester 14 was
derived from the enantiomer of 11 (Scheme 4). From this, the ab-
solute configuration (2R,3R,4S) of 11 was confirmed by X-ray
analysis (Fig. 3). On the basis of the absolute configuration of 14, we
propose a hypothetical transition state giving anti-Felkin–Anh
product with 2R,3R,4S (Fig. 4).
3. Conclusion
We have found Felkin–Anh selectivity in reductive aldol cou-
pling reaction of 2-phenylpropionaldehyde as a probe acceptor
with several unsaturated esters by use of achiral and chiral
Rh(Phebox) catalysts. These findings will provide an important
means of catalytic construction of multiple stereocenters including
asymmetric synthesis with transition metal complexes.
Finally, we employed three
a,b-unsaturated esters, namely
crotonate 8, cinnamate 9, and methacrylate 10, for the coupling
Me
Me
Table 1
S
i-Pr
O
O
Coupling reaction of 2-phenylpropanal and tert-butyl acrylate with achiral
Me
Me
N
N
Rh(Phebox) catalyst
OAc
OAc
1 mol%
Rh OH2
OAc
Rh OH2
OAc
Rh(Phebox) 1a
Me
(EtO)2MeSiH
H
+
N
N
Ph
CO2t-Bu
50 °C, 0.5 h
then F-
O
Me
Me
O
O
S
i-Pr
5
6
1a
1b
Me
Me Me
Rh(Phebox) cat.1
Ph
H
H
(EtO)2MeSiH
Ph
Ph
CO2t-Bu
+
CO2t-Bu
50 °C,0.5 h
then H3O+
O
O
OH
anti,syn (Felkin-Anh)
7
(S)-5
2
3
Me
β
Ph
Aldehyde
Yield of 7 (%)
dr
ee (%) of anti-Felkin–Anh
Racemic
α
CO2t-Bu
5
84
93
94
84
78
73
69a:21:7:3
72a:21:6:1
73a:19:7:1
68a:20:10:2
74a:18:7:1
79a:15:5:1
OH
4
5b
Racemic
Racemic
93e
5c
(S)-5d
(S)-5d,b
(S)-5d,c
cat. yield of 4 anti:syn ee of anti
ref.
91e
93e
1a
94%
91%
96:4
95:5
-
3a
3b
a
1b
91%a
anti-Felkin–Anh.
Me2PhSiH.
MPh2SiH.
92% ee.
(2R,3R,4S).
b
c
a (2R,3S)
d
e
Scheme 2. Rh(Phebox) catalyzed reductive aldol coupling of benzaldehyde and acry-
late (Refs. 3a and b).

9410
T. Hashimoto et al. / Tetrahedron 64 (2008) 9408–9412
t-BuO
t-BuO
Ot-Bu
H
H
H
Rh
*
*
Rh
Rh
O
O
O
Re
Me
Si
Me
Me
O
O
O
H
Ph
>>
H
Ph
Me
H
H
H
S
S
H
Me
Me
Ph
via Rh-E(O)-enolate
ii
i
favored
disfavored
t-BuO
anti,Felkin-Anh
anti,anti-Felkin-Anh
>>
H
*
Rh
Me Me
Me Me
O
Si
Me
β
β
O
γ
γ
α
α
Ph
CO2t-Bu
Ph
CO2t-Bu
H
H
Me
OH
OH
R
4
Ph
iii
t-BuO
H
Figure 2. Hypothetical transition model for chiral Rh(Phebox) catalyzed reductive
coupling reaction with chiral aldehydes.
Rh
O
Me
O
H
Me
1 mol%
Rh(Phebox) 1b
(EtO)2MeSiH
H
R
Me
Ph
H
+
Ph
CO2t-Bu
Figure 1. Hypothetical transition model for Rh(Phebox) catalyzed reductive coupling
50 °C, 0.5 h
then F-
O
reaction.
(S)-5
92% ee
8 R = Me
9 R = Ph
R
Me
4. Experimental
β
γ
α
Ph
CO2t-Bu
OH
anti,syn (Felkin-Anh)
4.1. General
NMR spectra were obtained in CDCl3 solution at 25 ꢀC. 1H NMR
chemical shifts are reported in
to the singlet at 7.26 ppm for chloroform. IR spectra were recorded
with a JASCO FT/IR-230 spectrometer. Rh(Phebox) catalysts were
synthesized by the method reported previously.3b,10
11 R = Me 61% dr = >98:2 (others), 98% ee
12 R = Ph 76% dr = >91:9 (others), 97% ee
d units, in parts per million relative
Me Me
Me
as above
β
γ
Ph
CO2t-Bu
Me
CO2t-Bu
OH
10
Table 2
syn (Felkin-Anh)
Coupling reaction of 2-phenylpropanal and tert-butyl acrylate with chiral Rh(Phe-
13 61% dr = 88:12
box) catalyst
91% ee for syn, 81% ee for anti
1 mol%
Rh(Phebox) 1b
Me
Scheme 3. Coupling reaction of (S)-2-phenylpropanal and other a,b-unsaturated
(EtO)2MeSiH
esters with chiral Rh(Phebox) catalyst.
H
H
+
Ph
Ph
CO2t-Bu
50 °C, 0.5 h
then F-
O
O
4.2. Typical reactions
5
6
4.2.1. The reaction of 2-phenylpropionaldehyde and tert-butyl
acrylate with Rh(Phebox) 1a
In a 25 mL flask, Rh(Phebox) 1a (5.4 mg, 0.01 mmol) was placed
under argon atmosphere. After toluene (1.0 mL), 2-phenyl-
propionaldehyde (134 mg, 1.0 mmol), and tert-butyl acrylate
(256 mg, 2.0 mmol) were added to the flask at room temperature,
Me Me
Me
Ph
CO2t-Bu
OH
anti,syn (Felkin-Anh)
7
(S)-5
Aldehyde
Yield of 7 (%)
dr
ee (%) of anti-Felkin–Anh
Me
5
70
83
81
72
75
55a:35:8:2
88a:4:7:1
76
(S)-5b
(S)-5b,d
(S)-5b,e
(R)-5f
99c
98c
98c
71g
Cl
CO2t-Bu
DCC, DMAP
Camphorsultam
derivative
80a:4:15:1
88a:2:9:1
2R
Me
Cl
Me
3R
Me
Ph
O
20a:65g:14:1
4S
Ph
CO2t-Bu
CH2Cl2, r.t.
a
O
OH
anti-Felkin–Anh.
92% ee.
O
O
b
c
d
e
f
N
11
S
73%
(2R,3R,4S).
Me2PhSiH.
MPh2SiH.
95% ee.
O
14
g
Scheme 4. Synthesis of the sulfonamide-ester 14.
anti,anti-Felkin–Anh (2R,3R,4R).

T. Hashimoto et al. / Tetrahedron 64 (2008) 9408–9412
9411
HRMS: (MþH) m/z, found: 265.1806; calcd (C16H25Oþ3 ): 265.1798;
LC: DAICEL CHIRALPAC AD-H, eluent¼hexane/2-propanol (99:1,
0.7 mL/min), retention time¼12.2 min (major), 14.7 min (minor),
>99% ee; for second major (anti,anti), 17.0 min, 18.0 min. The
corresponding methyl ester is a known compound in which
anti, -syn-stereochemistry for the four diastereomers were
determined; 1H NMR spectra were measured in CCl4.11
a,b-
b,g
4.2.4. The reaction of (S)-2-phenylpropionaldehyde and tert-butyl
crotonate with Rh(Phebox) 1b
The reaction with 1b (5.4 mg, 0.01 mmol) and tert-butyl croto-
nate (284 mg, 2.0 mmol) was carried out as described above. After
the reaction was completed, the mixture was treated with DMF
(2.5 mL), water (1 mL), KF (290 mg, 5.0 mmol), and TBAF (1 M in
THF, 0.2 mL) at 50 ꢀC for 16 h. After water (15 mL) was added, the
mixture was extracted with ethyl acetate. After the residue con-
centrated, dried over magnesium sulfate, and purified by silica gel
column chromatography (ethyl acetate/hexane¼20:1 as eluent) to
give 11 (171 mg, 0.61 mmol, 61%); diastereomer ratio, 98:2 (others),
determined by 1H NMR. Compound 11 (major, anti,syn): colorless
Figure 3. Molecular structure of 14.
diethoxymethylsilane (295 mg, 2.2 mmol) was added at 50 ꢀC. The
mixture was stirred for 30 min at 50 ꢀC. Water (1 mL), methanol
(1 mL), KF (5 mmol), and TBAF (1 mL, 1 M in THF) were added, and
the mixture was extracted with ethyl acetate. The extract was dried
over magnesium sulfate, concentrated, and the residue was puri-
fied by silica gel column chromatography (ethyl acetate/
hexane¼20:1 as eluent) to give tert-butyl 3-hydroxy-2-methyl-
4-phenylpentanoate 7 (222 mg, 0.84 mmol, 84%) as colorless oil;
diastereomer ratio of 69:21:7:3 was determined by 1H NMR
oil; 1H NMR (500 MHz, CDCl3):
d
0.86 (t, J¼7.5 Hz, 3H), 1.37 (d,
J¼6.5 Hz, 3H), 1.48 (s, 9H), 1.61 (m, 1H), 1.75 (m, 1H), 2.06 (m, 1H),
2.75 (m, 1H), 3.15 (d, J¼9.5 Hz, 1H), 3.62 (m, 1H), 7.16 (m, 2H), 7.23
(m, 1H), 7.28–7.32 (m, 2H); 13C NMR (125 MHz, CDCl3): 11.7, 18.0,
23.6, 28.2, 45.1, 49.3, 77.1, 81.3, 126.5, 127.6, 128.5, 144.6, 175.8; IR
3620–3300, 1704 cmꢁ1; FAB-HRMS: (MþH) m/z, found:
(500 MHz, CDCl3): for CHOH,
d 3.54 (m, major), 3.72 (m, second
(neat)
n
279.1962; calcd (C17H27Oþ3 ): 279.1955; LC: DAICEL CHIRALCEL OD-
H, eluent¼hexane/2-propanol (99:1, 0.7 mL/min), retention time¼
6.4 min (major), 7.4 min (minor), 98% ee.
major), 4.03 (m, minor), 4.00 (m, minor); anti,syn, anti,anti, syn,syn
(tentatively), syn,anti (tentatively).
4.2.2. The reaction of (S)-2-phenylpropionaldehyde and tert-butyl
acrylate with Rh(Phebox) 1a
4.2.5. The reaction of (S)-2-phenylpropionaldehyde and tert-butyl
cinnamate with Rh(Phebox) 1b
(S)-2-phenylpropionaldehyde (134 mg, 1.0 mmol, 92% ee) was
used, which was prepared by use of commercially available (S)-
(þ)-2-phenylpropionic acid via methyl esterification with
TMSCHN2 in MeOH, reduction with DIBAL at ꢁ78 ꢀC followed by
oxidation with IBX in DMSO at room temperature in ca. 70% yield in
three steps. The reaction and purification were carried out as de-
scribed above to give 7 (223 mg, 0.84 mmol, 84%); diastereomer
ratio was 68:20:10:2.
The reaction with 1b (5.4 mg, 0.01 mmol) and tert-butyl cinna-
mate (408 mg, 2.0 mmol) was carried out as described above. The
compound 12 was obtained in 76% yield (259 mg, 0.76 mmol); di-
astereomer ratio, 91:9 (others), determined by 1H NMR; proportion
of the other isomers could not determined, the stereochemistry of
anti,syn was tentatively assigned based on the case of 7. Compound
12 (major, anti,syn): colorless oil; 1H NMR (500 MHz, CDCl3):
d 1.34
(s, 9H), 1.35 (d, J¼7.0 Hz, 3H), 2.45 (m, 1H), 2.77 (m, 1H), 2.89 (m,
1H), 2.99 (m,1H), 3.32 (d, J¼10.0 Hz,1H), 3.55 (m,1H), 7.03–7.07 (m,
4H), 7.17–7.28 (m, 6H); 13C NMR (125 MHz, CDCl3): 18.7, 27.9, 36.3,
45.4, 48.9, 76.4, 81.4, 126.3, 126.5, 127.5, 128.2, 128.5, 129.1, 138.4,
4.2.3. The reaction of (S)-2-phenylpropionaldehyde and tert-butyl
acrylate with Rh(Phebox) 1b
The reaction with 1b (5.4 mg, 0.01 mmol) was carried out as
described. After the reaction was completed, the mixture was
treated with DMF (2.5 mL), water (1 mL), KF (290 mg, 5.0 mmol),
and TBAF (1 M in THF, 0.2 mL) at 50 ꢀC for 9 h. After water (15 mL)
was added, the mixture was extracted with ethyl acetate. After the
residue concentrated, dried over magnesium sulfate, and purified
by silica gel column chromatography (ethyl acetate/hexane¼20:1
as eluent) to give 7 (219 mg, 0.83 mmol, 83%); diastereomer ratio
was 88:4:7:1. Compound 7 (major, anti,syn): colorless oil; 1H NMR
144.4, 175.1; IR (neat)
n
3620–3300, 1698 cmꢁ1; FAB-HRMS: (MþH)
m/z, found: 341.2112; calcd (C22H29Oþ3 ): 341.2111; LC: DAICEL
CHIRALPAC AD-H, eluent¼hexane/2-propanol (99:1, 0.7 mL/min),
retention time¼22.8 min (minor), 27.8 min (major), 97% ee.
4.2.6. The reaction of (S)-2-phenylpropionaldehyde and tert-butyl
methacrylate with Rh(Phebox) 1b
The reaction with 1b (5.4 mg, 0.01 mmol) and tert-butyl meth-
acrylate (284 mg, 2.0 mmol) was carried out as described above.
The compound 13 was obtained in 61% (169 mg, 0.61 mmol) as
white solids; diastereomer ratio, 88:12, determined by 1H NMR: for
(500 MHz, CDCl3):
d
1.20 (d, J¼7.5 Hz, 3H), 1.37 (d, J¼7.0 Hz, 3H),
1.47 (s, 9H), 2.28 (dq, J¼4.5, 7.5 Hz, 1H), 2.84 (dq, J¼7.0, 7.5 Hz, 1H),
3.55 (dd, J¼4.5, 8.0 Hz,1H), 7.17–7.23 (m, 3H), 7.28–7.32 (m, 2H); 13
C
NMR (125 MHz, CDCl3): 15.6, 17.1, 28.1, 42.3, 44.5, 78.8, 81.1, 126.5,
CHO,
and syn stereochemistry was tentatively assigned. Compound 13
(major, syn): 1H NMR (500 MHz, CDCl3):
1.14 (s, 3H), 1.16 (s, 3H),
d 3.72 (syn), 3.81 (anti) and for OH, d 3.19 (anti), 3.23 (syn); anti
127.6, 128.5, 144.7, 176.1; IR (neat)
n
3620–3300, 1727 cmꢁ1; FAB-
d
1.26 (d, J¼7.0 Hz, 3H), 1.47 (s, 9H), 2.96 (m, 1H, CHPh), 3.23 (d,
J¼8.5 Hz, 1H, OH), 3.72 (m, 1H), 7.17–7.20 (m, 1H), 7.25–7.30 (m,
4H); (minor, anti): 1.14 (s, 3H), 1.20 (s, 3H), 1.31 (d, J¼7.0 Hz, 3H),
1.32 (s, 9H), 2.92 (m, 1H), 3.19 (d, J¼8.5 Hz, 1H), 3.81 (m, 1H), 7.17–
7.20 (m, 1H), 7.25–7.30 (m, 4H); 13C NMR (125 MHz, CDCl3): 16.5,
21.8, 24.9, 27.9, 41.7, 47.3, 81.0, 81.2, 126.1, 127.6, 128.3, 146.9, 177.3;
t-BuO
anti,Felkin-Anh
H
*
Rh
Me Et
O
Et
favored
3
O
4
2
Ph
CO2t-Bu
H
Ph
OH
2R,3R,4S
Figure 4. Hypothetical transition state.
S
H
IR (KBr disk)
n
3620–3300, 1701 cmꢁ1; FAB-HRMS: (MþH) m/z,
Me
found: 279.1974; calcd (C17H27Oþ3 ): 279.1955; LC: DAICEL
CHIRALPAC AD-H, eluent¼hexane/2-propanol (99:1, 0.7 mL/min),

9412
T. Hashimoto et al. / Tetrahedron 64 (2008) 9408–9412
retention time: for syn, 20.0 min (major), 30.5 min (minor), 91% ee;
for anti, 12.8 min (minor), 14.1 min (major), 81% ee.
from The Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; deposit@ccdc.cam.au.uk.
Acknowledgements
4.3. Synthesis of sulfonamide-ester 14
This work was partly supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan (Concerto Catalysts, 460:18065011), the
Japan Society for the Promotion of Science (18350049), G-COE in
Chemistry (Nagoya University).
To a solution of 11 (84 mg, 0.30 mmol, >98% ee) and N-(2-car-
boxy-4,5-dichlorobenzoyl)-(ꢁ)-10,2-camphorsultam
(TCI-1683)
(195 mg, 0.45 mmol) in dichloromethane (8 mL), DCC (93 mg,
0.45 mmol) and DMAP (5.5 mg) were added at 0 ꢀC, and then the
mixture was stirred for 6 days at room temperature. After filtration
through Celite column, the filtrate was concentrated to give the
crude product, which was purified by silica gel column chroma-
tography (ethyl acetate/hexane as eluent) to give the corresponding
sulfonamine ester (153 mg, 0.22 mmol, 73%). Compound 14: white
Supplementary data
Analysis for NMR, IR, and LC charts of the products are provided.
Supplementary data associated with this article can be found in the
online version, at doi:10.1016/j.tet.2008.07.092.
solids; mp: 117–118 ꢀC; 1H NMR (500 MHz, CDCl3):
d 0.069 (s, 1H),
0.74 (t, J¼7.5 Hz, 3H), 0.97 (s, 3H), 1.20–1.23 (m, 6H), 1.30 (m, 1H),
1.47 (m, 1H), 1.51 (s, 9H), 1.64 (m, 1H), 1.95 (m, 3H), 2.15–2.26 (m,
2H), 2.53 (m, 1H), 3.33 (m, 1H), 3.39 (d, J¼14.0 Hz, 1H), 3.43 (d,
J¼14.0 Hz, 1H), 4.10 (m, 1H), 5.37 (dd, J¼11.0, 2.0 Hz, 1H), 7.20–7.25
(m, 1H), 7.28–7.35 (m, 4H), 7.53 (s, 1H), 8.21 (s, 1H); 13C NMR
(125 MHz, CDCl3): 1.0, 11.8, 19.1, 20.1, 20.8, 22.6, 26.5, 26.9, 28.2,
33.1, 37.7, 42.5, 44.7, 47.8, 48.5, 49.9, 53.0, 65.7, 79.3, 80.8, 126.9,
127.8, 128.0, 128.7, 131.1, 131.6, 134.6, 135.4, 137.0, 143.1, 162.7, 165.2,
References and notes
1. (a) Nishiyama, H.; Shiomi, T. Metal Catalyzed Reductive C–C Bond Formation. In
Topics in Current Chemistry; Krische, M. J., Ed.; Springer: Berlin, Heidelberg,
2007; Vol. 279, p 105; (b) Iida, H.; Krische, M. J. Metal Catalyzed Reductive C–C
Bond Formation. In Topics in Current Chemistry; Krische, M. J., Ed.; Springer:
Berlin, Heidelberg, 2007; Vol. 279, p 77; (c) Motherwell, W. B. Pure Appl. Chem.
2002, 74, 135; (d) Jang, H.-Y.; Krische, M. J. Acc. Chem. Res. 2004, 37, 653; (e)
Chiu, P. Synthesis 2004, 2210.
2. Zhao, C.-X.; Duffey, M. O.; Taylor, S. J.; Morken, J. P. Org. Lett. 2001, 3, 1829.
3. (a) Nishiyama, H.; Shiomi, T.; Tsuchiya, Y.; Matsuda, I. J. Am. Chem. Soc. 2005,
127, 6972; (b) Ito, J.; Shiomi, T.; Nishiyama, H. Adv. Synth. Catal. 2006, 348, 1234;
(c) Shiomi, T.; Ito, J.; Yamamoto, Y.; Nishiyama, H. Eur. J. Org. Chem. 2006, 5594;
(d) Hashimoto, T.; Shiomi, T.; Ito, J.; Nishiyama, H. Tetrahedron 2007, 63, 12883;
(e) Nishiyama, H.; Ishikawa, J.; Shiomi, T. Tetrahedron Lett. 2007, 48, 7841.
4. Jung, C.-K.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 17051.
171.1; IR (KBr disk)
n
1729, 1678 cmꢁ1; FAB-HRMS: (MþH) m/z,
25
found: 692.2200; calcd (C35H44Cl2NO7Sþ): 692.2210; [
a
]
ꢁ42.6
D
(c 1.09, CHCl3).
4.4. X-ray analysis of 14
5. For example: (a) Paterson, I.; Lyothier, I. J. Org. Chem. 2005, 70, 5494; (b)
Guindon, Y.; Brazeau, J.-F. Org. Lett. 2004, 6, 2599; (c) Kiyooka, S.; Shahid, K. A.;
Goto, F.; Okazaki, M.; Shuto, Y. J. Org. Chem. 2003, 68, 7967; (d) Dias, L. C.; de
Oliveira, L. G.; de Sousa, M. A. Org. Lett. 2003, 5, 265; (e) Shahid, K. A.; Mur-
sheda, J.; Okazaki, M.; Shuto, Y.; Goto, F.; Kiyooka, S. Tetrahedron Lett. 2002, 43,
6377; (f) Yang, H. W.; Zhao, C.; Romo, D. Tetrahedron 1997, 53, 16471; (g) For
diastereofacial selectivity of aldol reactions, see: Paterson, I.; Franklin, A. S.
Tetrahedron Lett. 1994, 35, 6925; (h) Roush, W. R. J. Org. Chem. 1991, 56, 4151.
6. (a) For Zimmerman–Traxler model, see: Zimmerman, H. E.; Traxler, M. D. J. Am.
Chem. Soc. 1957, 79, 1920; (b) Clayden, J.; Greeves, N.; Warren, S.; Wothers, P.
Organic Chemistry; Oxford University Press: New York, NY, 2001; p 900.
Single crystals of 14 suitable for X-ray diffraction study were
obtained from a hot hexane solution. The diffraction data were
collected on a Bruker SMART APEX CCD diffractometer with
graphite monochromated Mo K
a
radiation (l¼0.71073 Å). An em-
pirical absorption correction was applied using SADABS. The
structure was solved by direct method and refined by full-matrix
least-square on F2 using SHELXTL. All non-hydrogen atoms except
the disordered atoms and the solvent molecule were refined with
anisotropic displacement parameters. The disorders at C17 and
C50–52 were refined in the ratio of 35:65 and 62:38, respectively.
Crystallographic data for 14: C38H50Cl2NO7S; Mr¼735.75; temper-
ature 133 K; monoclinic, P212121; a¼14.548(6), b¼18.519(8),
´
7. For Felkin–Anh model: (a) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett.
1968, 2199; (b) Mengel, A.; Reiser, O. Chem. Rev. 1999, 99, 1191; Also see: (c)
Smith, M. B.; March, J. Advanced Organic Chemistry, Reactions, Mechanisms, and
Structure, 6th ed.; John Wiley & Sons: Hoboken, 2007; Chapter 4,
p 169
and references cited therein; (d) Wyatt, P.; Warren, S. Organic Synthesis, Strategy
and Control; John Wiley and Sons: Chichester, UK, 2007; Chapter 21, p 429 and
Chapter 30, p 681.
8. Use of other hydrosilanes: Me2PhSiH, 85% yield with 5, 46:41:7:6 (major, 77%
ee); MePh2SiH, 75% yield with 5, 50:36:10:4 (major, 80% ee).
9. When benzyl group was employed in place of isopropyl group of Rh(Phebox)
1b, the yield of 7 with (S)-5 was 72% with 84:5:8:3 diastereomer ratio and 99%
ee for anti/syn.
c¼28.785(12) Å;
V¼7755(6) Å3;
Z¼8;
rcalcd¼1.260 Mg/m3;
m
¼0.269 mmꢁ1
; reflections collected 55 697, independent re-
flections 18 068 [R(int)¼0.0898]; data/restraints/parameters
18 068/46/874; goodness-of-fit on F2: 0.992; final
R indices
[I>2
s
(I)] R1¼0.0662, wR2¼0.1398; R indices (all data) R1¼0.1225,
wR2¼0.1639; largest diff. peak/hole 0.471 and ꢁ0.478 e Åꢁ3. CCDC
690605 contains the supplementary crystallographic data. The data
can be obtained free of charge via http://www.ccdc.cam.au.ac.uk or
10. Kanazawa, Y.; Tsuchiya, Y.; Kobayashi, K.; Shiomi, T.; Ito, J.; Kikuchi, M.;
Yamamoto, Y.; Nishiyama, H. Chem.dEur. J. 2006, 12, 63.
11. Matsumoto, T.; Hosoda, Y.; Mori, K.; Fukui, K. Bull. Chem. Soc. Jpn. 1972, 45, 3156.