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

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.

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

References

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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.

<A NAME="RU12705ST-19">19</A>

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).