One catalyst for two distinct reactions: sequential asymmetric hetero Diels–Alder reaction and diethylzinc addition

Abstract

This paper describes the successful development of a series of chiral zinc catalysts containing ( R)-3,3′-Br 2-BINOL ligand and various diimine activators for enantioselective HDA reaction of Danishefsky's diene with aldehydes through a combinatorial approach, affording the corresponding 2,3-dihydro-4 H-pyran-4-one derivatives in excellent yields and enantioselectivities. The application of this type of catalysts was also extended to the diethylzinc addition to the benzaldehyde, affording the corresponding secondary alcohol with up to 94.5% ee under optimized conditions. On the basis of these facts, the integration of two distinct enantioselective reactions, HDA and diethylzinc addition reactions, has been realized in one-pot with the promotion of a single chiral zinc catalyst in a sequential manner. The impact of diimine additive on the catalytic system of HDA reaction was also investigated by probing the nonlinear effect of reaction system. The positive nonlinear effect exhibited in the catalytic system could be attributed to the poor solubility of the heterochiral zinc species. On the basis of various experimental findings disclosed in this research, a possible mechanism for the asymmetric induction in the 3,3′-Br 2-BINOL/Zn/diimine catalyzed enantioselective HDA reaction of Danishefsky's diene with aldehydes was outlined.