Rapid Screening of Organocatalysts for Michael Additions to Enals

Significance

An efficient combinatorial strategy for the rapid catalyst screening and optimization of organocatalysts for the Michael addition to α,β-unsaturated aldehydes was reported by the authors. Based on the principle of microscopic reversibility, the intermediates of retro-Michael addition of a pair of quasienantiomeric adducts 1a and 2a (opposite configuration) can be detected to determine the enantioselectivity of the forward reaction. Thus, the ratio of the mass signal intensities of intermediates 1c and 2c reflects the enantioselectivity of the catalyst (k _a/k _b ˜ M_1c/M_2c) due to the identical transition states of the forward and back reaction. Catalysts 3 and 4, in which the ­TBDMS or TIPS groups are superior to the TMS or TES groups, were identified with this method.