Direct Noncovalent Activation of α,ß-Unsaturated Aldehydes for the Stereodivergent Synthesis of Substituted Cyclohexenes.

ABSTRACT

HOMO-raising noncovalent activation of α-aryl α,ß-unsaturated aldehydes using a bifunctional Brønsted base catalyst is achieved. The catalytically generated dienolate intermediate undergoes all-carbon [4+2] cyclizations with nitroolefins, leading to chiral cyclohexenes with four contiguous stereocenters in high yields and with excellent enantioseletivity. Furthermore, the diastereodivergent synthesis of the products is realized by introducing a second steric control to the bifunctional catalyst; 4 isomers out of 16 possible stereoisomers of the products were selectively produced by simple use of two catalysts and their (pseudo)enantiomers. The results presented here provide new insights into the remote activation of the carbonyl functionality as well as the stereodivergent synthesis of complex chiral molecules with multiple stereocenters.