LETTER
Conjugate Reduction of a,b-Unsaturated Aldehydes
3345
Rh(Phebox) 2 (1 mol%)
(EtO)2MeSiH (1.5 equiv)
CHO
toluene
CHO
60 °C
Me
then TBAF, KF
Me
9
10
Rh(Phebox) 2 (1 mol%)
(EtO)2MeSiH (1.5 equiv)
Me
Me
CHO
CHO
toluene
30 °C, 1 h
then TBAF, KF
Me
Me
Me
Me
11
12
40% (92% ee)[1,2-redn 56%]
Scheme 3 Asymmetric conjugate reduction
solid; mp 135–136 °C; 1H NMR (300 MHz, CDCl3): d =
8.27 (t, J = 1.5 Hz, 1 H), 8.11 (d, J = 1.5 Hz, 2 H), 4.30 (t,
In conclusion, we have disclosed that readily available
Rh(Phebox) acetato complexes exhibit efficient catalytic
activity in the hydrosilylative conjugate reduction of enal
derivatives. The selective conjugate reduction was at-
tained by the choice of both the hydrosilane and the cata-
lyst. Interestingly, it was found, that although high
asymmetric induction was attained in two cases of the b-
methyl enals, the b-methyl group exerted a significant in-
fluence on the chemoselectivity, 1,2- or 1,4-reduction, to
decrease the selectivity of the 1,4-reduction. We are now
studying efficient chemoselective and enantioselective re-
duction conditions for a variety of enals.
J = 9.0 Hz, 2 H), 4.07 (t, J = 9.0 Hz, 2 H), 1.36 (s, 9 H); 13
NMR (75 MHz, CDCl3): d = 31.33, 35.06, 55.06, 67.66,
125.1, 127.6, 127.8, 151.5, 164.1. A mixture of t-Bu-Phebox
(817 mg, 3.0 mmol), RhCl3(H2O)3 (870 mg, 3.3 mmol),
NaHCO3 (252 mg, 3.0 mmol), MeOH (30 mL) and H2O (1
mL) was heated at 60 °C for 5 h. After concentration, the
residue was purified by column chromatography (EtOAc–
hexane) to give the corresponding chloro complex Rh(t-Bu-
Phebox)Cl2(H2O) (872 mg, 63%). The chloro complex was
treated at r.t. for 15 h with AgOAc (1.25 g) in CH2Cl2 (40
mL) and then purified by column chromatography (EtOAc
→ EtOAc–MeOH, 10:1) to give 1 (855 mg, 89%) as a
yellow solid; mp 126 °C (dec.); 1H NMR (300 MHz,
CDCl3): d = 7.67 (s, 2 H), 6.51 (br s, 2 H), 4.88 (t, J = 9.6 Hz,
2 H), 4.13 (t, J = 9.6 Hz, 2 H), 1.68 (s, 6 H), 1.41 (s, 9 H);
13C NMR (75 MHz, CDCl3): d = 24.01, 31.82, 35.18, 50.83,
71.20, 124.9, 130.9, 146.7, 172.7 (JRh–C = 4.0 Hz), 182.3,
184.6 (JRh–C = 23.9 Hz); IR (KBr): 1720 cm–1.
C
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science and Tech-
nology, Japan.
(8) For the synthesis of 2, see ref 1a.
(9) Typical procedure (run 6, Table 1): To a solution of
cinnamaldehyde (132 mg, 1.00 mmol) and 2 (5.4 mg, 0.010
mmol) in toluene (1.0 mL) at 30 °C, was added
References and Notes
(1) (a) Kanazawa, Y.; Tsuchiya, Y.; Kobayashi, K.; Shiomi, T.;
Itoh, J.; Kikuchi, M.; Yamamoto, Y.; Nishiyama, H. Chem.
Eur. J. 2006, 12, 63. (b) Tsuchiya, Y.; Kanazawa, Y.;
Shiomi, T.; Kobayashi, K.; Nishiyama, H. Synlett 2004,
2493. (c) Nishiyama, H.; Shiomi, T.; Tsuchiya, Y.; Matsuda,
I. J. Am. Chem. Soc. 2005, 127, 6972.
(2) Ojima, I.; Kogure, T. J. Org. Chem. 1982, 1, 1390.
(3) Keinan, E.; Greenspoon, N. J. Am. Chem. Soc. 1986, 108,
7314.
(4) Lipshutz, B. H.; Keith, J.; Papa, P.; Vivian, R. Tetrahedron
Lett. 1998, 39, 4627.
(5) Brestensky, D. M.; Stryker, J. M. Tetrahedron Lett. 1989,
30, 5677.
(6) (a) Yang, J. W.; Fonseca, M. T. H.; List, B. Angew. Chem.
Int. Ed. 2004, 43, 6660. (b) Yang, J. W.; Fonseca, M. T. H.;
Vignola, N.; List, B. Angew. Chem. Int. Ed. 2005, 44, 108.
(c) Ouellet, S. G.; Tuttle, J. B.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2005, 127, 32.
(7) The tert-butyl group of Phebox is important as it increases
solubility. The t-Bu-Phebox ligand was prepared from 5-
tert-butylisophthalic acid (Aldrich 362514). Using SOCl2,
the acid chloride was formed first, followed by reaction with
2-aminoethanol to give the amide, this was then cyclized
using MsCl and Et3N to give t-Bu-Phebox as a colorless
diethoxymethylsilane (0.24 mL, 1.5 mmol). The mixture
was stirred for 1 h. After confirmation of complete
consumption of the aldehyde, the mixture was cooled to 0 °C
and TBAF (0.4 mL, 1 M in THF), KF (2 mmol), and MeOH
(1 mL) were added. The mixture was stirred for 1 h. Then aq
NaHCO3 was added, and the mixture was extracted with
EtOAc. After concentration, the residue was purified by
column chromatography (hexane–EtOAc) to give the
dihydrocinnamaldehyde in 97% (130 mg).
(10) (R)-10: [a]D24.5 –32.6 (c 1.01, EtOH) {Lit. [a]D22 +32.9° (c
1.00, EtOH)} for 93% ee of S6c; 1H NMR (300 MHz,
CDCl3): d = 9.72 (t, J = 2.1 Hz, 1 H), 7.28–7.34 (m, 2 H),
7.18–7.23 (m, 3 H), 3.37 (m, 1 H), 2.76 (ddd, J = 16.5, 6.9,
2.1 Hz, 1 H), 2.66 (ddd, J = 16.5, 7.5, 2.1 Hz, 1 H), 1.32 (d,
J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3): d = 22.31,
34.39, 51.76, 126.3, 126.5, 128.4, 145.1, 201.3; IR (film):
1723 cm–1; GC: SUPELCO BETA-DEX 325 (30 m), 60 kPa,
100 °C, r.t., 54.9 min for R and 56.2 min for S.
(11) (S)-12: [a]D25.4 –15.2 (c 1.00, CHCl3) {Lit. [a]D24 –16.2 (c
1.00, CHCl3)} for 98% ee of S: Yamamoto, T.; Shimada, A.;
Ohmoto, T.; Matsuda, H.; Ogura, M.; Kanisawa, T. Flavour
Fragr. J. 2004, 19, 121.
Synlett 2006, No. 19, 3343–3345 © Thieme Stuttgart · New York