Highly enantioselective cyanoformylation of aldehydes catalyzed by a mononuclear salen-Ti(OiPr)₄ complex produced in situ

An efficient enantioselective cyanoformylation of aldehydes with ethyl cyanoformate, catalyzed by a salen-Ti(OiPr)₄ complex generated in situ, has been developed. Studies of non-linear effects indicated that the mononuclear salen-titanium complex, and not a heterochiral complex, played a key role in the stereodiscriminating step of the reaction. During the preparation of the catalyst, the addition of isopropyl alcohol was shown to avoid the formation of a heterochiral complex. In the presence of 5 mol-% catalyst, the reaction can be carried out in excellent yields (up to 99%) and with high enantioselectivities (up to 91 % ee). From preliminary studies, a transition state to explain the origin of the asymmetric induction has been proposed.