Highly enantioselective catalytic Michael reaction of α-substituted malonates using La-linked-BINOL complex in the presence of HFIP (1,1,1,3,3,3-hexafluoroisopropanol)

A catalytic asymmetric Michael reaction of alpha-substituted malonates with broad generality was developed using the La-linked-BINOL complex. To enhance the reactivity of unreactive a-substituted malonates, we examined the effects of concentration and additives; 1.0 M was the best concentration and HFIP (1.1,1.3,3,3-hexafluoroisopropanol) accelerated the reaction efficiently. Under the optimized conditions, the catalytic asymmetric Michael reaction of a variety of x-substituted malonates proceeded successfully in high yield (up to 93%) and excellent enantiomeric excess (up to 99% ee). The addition of HFIP was also effective for the reaction of nonsubstituted malonates. In this case, 5 mol% of the La-linked-BINOL complex was sufficient for completion of the reaction in approximately 24 h. Moreover, several Michael adducts were readily converted to the bicyclic compounds. (C) 2002 Elsevier Science Ltd. All rights reserved.