Conjugate Reduction of α,β-Unsaturated Aldehydes with Rhodium(bis­oxazolinylphenyl) Catalysts

Abstract

α,β-Unsaturated aldehydes were selectively reduced using rhodium(bisoxazolinylphenyl) complexes to give exclusive 1,4-selectivity in the combination of alkoxyhydrosilanes.

Key words

rhodium - conjugate reduction - unsaturated aldehyde - hydrosilylation - asymmetric catalysis

References and Notes

• 1a Kanazawa Y. Tsuchiya Y. Kobayashi K. Shiomi T. Itoh J. Kikuchi M. Yamamoto Y. Nishiyama H. Chem. Eur. J.  2006,  12:  63 
• 1b Tsuchiya Y. Kanazawa Y. Shiomi T. Kobayashi K. Nishiyama H. Synlett  2004,  2493 
• 1c 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 BH. Keith J. Papa P. Vivian R. Tetrahedron Lett.  1998,  39:  4627 
• 5 Brestensky DM. Stryker JM. Tetrahedron Lett.  1989,  30:  5677 
• 6a Yang JW. Fonseca MTH. List B. Angew. Chem. Int. Ed.  2004,  43:  6660 
• 6b Yang JW. Fonseca MTH. Vignola N. List B. Angew. Chem. Int. Ed.  2005,  44:  108 
• 6c Ouellet SG. Tuttle JB. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  32 
• 11 (S)-12: [α]_D ^25.4 -15.2 (c 1.00, CHCl₃) {Lit. [α]_D ²⁴ -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 

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 solid; mp 135-136 °C; ¹H NMR (300 MHz, CDCl₃): δ = 8.27 (t, J = 1.5 Hz, 1 H), 8.11 (d, J = 1.5 Hz, 2 H), 4.30 (t, J = 9.0 Hz, 2 H), 4.07 (t, J = 9.0 Hz, 2 H), 1.36 (s, 9 H); ¹³C NMR (75 MHz, CDCl₃): δ = 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): δ = 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): δ = 24.01, 31.82, 35.18, 50.83, 71.20, 124.9, 130.9, 146.7, 172.7 (J _Rh-C = 4.0 Hz), 182.3, 184.6 (J _Rh-C = 23.9 Hz); IR (KBr): 1720 cm^-1.

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 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: [α]_D ^24.5 -32.6 (c 1.01, EtOH) {Lit. [α]_D ²² +32.9° (c 1.00, EtOH)} for 93% ee of S [6c] ; ¹H NMR (300 MHz, CDCl₃): δ = 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): δ = 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.