Diversity-based strategy for discovery of environmentally benign organocatalyst: diamine-protonic acid catalysts for asymmetric direct aldol reaction

Fifteen different diamines (4-18) and potonic acids have been screened in the catalytic asymmetric direct aldol reaction of three different aldehydes in acetone. These initial studies demonstrated that the secondary-tertiary diamine series is effective with regard to reactivity. In contrast, the primary-tertiary diamines 13 and 14 were proved to be a superb structural module to avoid dehydration. Further investigation led us to a new procedure for the preparation of diamine catalysts for synthetic convenience. This involves diamine-diacid salt 22, which acted not only as a catalyst backbone but also as a TfOH source. Salt 22-diamine 4 catalyst thus prepared was found to exhibit higher reactivity and selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.