Asymmetric synthesis of O-benzoyl cyanohydrins by reaction of aldehydes with benzoyl cyanide catalysed by BINOLAM–Ti(IV) complexes

The asymmetric cyanobenzoylation of aldehydes has been carried out for the first time, by reaction with benzoyl cyanide in a process catalysed by either (R)- or (S)-3,3′-bis(diethylaminomethyl)-1,1′-binaphthol BINOLAM–Ti(IV) complexes at room temperature and without additives. The reaction can be described as an overall cyano-O-benzoylation of aldehydes where a Lewis acid–Brönsted base (LABB) dual role for the catalyst induced firstly the key enantioselective hydrocyanation, which is then followed by O-benzoylation furnishing enantioenriched O-benzoyl cyanohydrins.

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(S)-2-(Benzyloxy)-2-phenylacetonitrileC15H12NO2Ee = 68%[α]D25=-7.7 (c 2, CHCl3)Source of chirality: (R)-BINOLAMAbsolute configuration: (S)

(R)-2-(Benzoyloxy)-2-(4-methoxyphenyl)acetonitrileC16H13NO2Ee = 56%[α]D25=+10.9 (c 1, CHCl3)Source of chirality: (S)-BINOLAMAbsolute configuration: (R)

(R)-2-(Benzoyloxy)-2-(4-chlorophenyl)acetonitrileC15H10ClNO4Ee = 58%[α]D25=+9.6 (c 1, CHCl3)Source of chirality: (S)-BINOLAMAbsolute configuration: (R)

(S)-2-(Benzoyloxy)-2-furylacetonitrileC13H9NO3Ee = 55%[α]D25=-2.9 (c 1, CHCl3)Source of chirality: (S)-BINOLAMAbsolute configuration: (S)

(R)-2-(Benzoyloxy)-3-nonenenitrileC16H19NO2Ee = 68%[α]D25=-4.3 (c 0.5, CHCl3)Source of chirality: (S)-BINOLAMAbsolute configuration: (R)

(R)-2-(Benzoyloxy)octanenitrileC15H19NO2Ee = 58%[α]D25=+10.1 (c 0.7, CHCl3)Source of chirality: (S)-BINOLAMAbsolute configuration: (R)

(R)-2-(Benzoyloxy)-4-phenylbutanenitrileC17H16NO2Ee = 65%[α]D25=+13.9 (c 2, CHCl3)Source of chirality: (S)-BINOLAMAbsolute configuration: (R)