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Synlett 2005(13): 1995-1998  
DOI: 10.1055/s-2005-871971
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereofacial Control in Asymmetric Cyanosilylation of Aldehydes Catalyzed by Novel S-Proline-Derived Titanium Complexes

Yun Bong Kim, Min Kyoun Kim, Sung Ho Kang, Yong Hae Kim*
Center for Molecular Design and Synthesis, Department of Chemistry, School of Molecular Science (BK-21), Korea Advanced Institute of Science and Technology, Taejon 305-701, Korea
Fax: +82(42)8692818; e-Mail: kimyh@kaist.ac.kr;
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Publication History

Received 30 April 2005
Publication Date:
20 July 2005 (online)

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Abstract

Asymmetric cyanosilylation of aryl aldehydes has been achieved utilizing catalytic amounts of novel chiral ligands. Chiral ligands of amino alcohols and aminophosphine gave S-configured cyanosilylated products with up to 84% ee. In contrast, C 2 -symmetric ligands resulted in R-configured products with up to 95% ee.

Key words

asymmetric catalysis - cyanohydrin - S-proline derivatives - stereoselectivity - Lewis acid/base catalysis

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2,6-Bis[2-(diphenylphosphinoylmethyl)octahydroindol-1-ylmethyl]-4-methylphenol(7); Typical Procedure 2,6-Bis(bromomethyl)-4-methylphenol (292 mg, 1 mmol) was added in one portion to a stirred and cooled solution of 2-(diphenylphosphinoylmethyl)octahydroindole (879 mg, 2 mmol) and K2CO3 (552 mg, 4 mmol) in anhyd DMF (5 mL). The ice bath was removed after the addition and the resulting solution was allowed to stir at r.t. for 24 h before it was diluted with H2O and Et2O. The two phases were separated and the aqueous phase was extracted with Et2O three times and the combined organic phases were washed H2O, brine, dried over MgSO4, and evaporated. The residue was purified by chromatography through a short slica gel column (EtOAc-hexane, 1:1) to give 7 in 64% yield (520 mg, yellow foam). [α]D 23 -79.8 (c 1, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 1.42-1.60 (m, 8 H), 1. 65-1.96 (m, 4 H), 2.06 (d, 2 H), 2.08-2.34 (m, 6 H), 2.12 (s, 3 H), 2.36 (t, 2 H), 2.84-2.93 (m, 4 H), 3.28 (d, 2 H), 3.38 (d, 2 H), 3.52 (s, 2 H), 3.96 (s, 2 H), 6.75 (s, 2 H), 7.31-7.38 (m, 10 H), 7.39-7.64 (m, 10 H). 13C NMR (75.5 MHz, CDCl3): δ = 20.36, 21.97, 31.34, 31.77, 32.92, 33.63, 52.50, 53.15, 53.54, 59.40, 60.00, 123.1, 128.6, 129.6, 129.7, 131.5, 135.0, 155.3. 31P NMR (121.5 MHz, CDCl3): δ = 29.31 (s). MS (MALDI-TOF): m/z calcd for C51H60N2O3P2, 810.4079; found, 811.0474.

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Asymmetric Cyanosilylation of Aldehydes (Table 4, entry 2); Typical Procedure To a solution of 7 (20.2 mg, 0.025 mmol) and O=PPh3 (139 mg, 0.5 mmol) in CH2Cl2 (5 mL), Ti(Oi-Pr)4 (1 M in toluene, 25 µL, 0.025 mmol) was added at r.t., and the mixture was stirred at 0 °C for 30 min under an argon atmosphere. To this solution, benzaldehyde (0.25 mol) was added after the addition of TMSCN (60 µL, 0.5 mmol) in CH2Cl2 (1 mL) at -20 °C. The reaction was monitored by TLC, after 24 h, the mixture was concentrated and then purified by silica gel chromatography (EtOAc-hexane, 1:4) to obtain phenyltrimethylsilanyloxyacetonitrile in 74% yield. 1H NMR (300 MHz, CDCl3): d = 0.08 (s, 9 H), 5.55 (s, 1 H), 7.40-7.60 (m, 5 H). After conversion to acetate, the enantiomeric excess was determined by HPLC on a Chiralcel OD column, hexane-i-PrOH, 99:1 (flow rate = 1.0 mL/min), t R (R) 12.92 min (major), t R (S) 14.80 min (minor).