Direct Catalytic Asymmetric Addition of Allylic Cyanides to Aldehydes for Expeditious Access to Enantioenriched Unsaturated δ-Valerolactones

摘要

Catalytic enantioselective C-C bond-forming reactions that proceed with perfect atom economy have received increasing attention as an environmentally benign chemical process. The integration of two phases, catalytic generation of active nucleophiles and enantioselective addition to certain electrophiles, is the key to the manifestation of the above-mentioned reactions. The feasibility of this is largely dependent on the nature of the pronucleophile; low-pK_a carbon pronucleophiles are favored and primarily used for efficient generation of carbanions. Our particular focus is the exploitation of high-pK_a carbon pronucleophiles through cooperative catalysis; Lewis acidic activation and Bronsted basic activation function synergistically to generate an active carbon nucleophile under mild conditions, thereby expanding the scope of atom-economical C-C bond-forming reactions. We have reported that allyl cyanide (1a) is a suitable Lewis basic pronucleophile that is chemoselectively activated by a soft Lewis acid through the nitrile functionality to enhance its acidity to be synergistically deprotonated by a hard Bronsted base (Figure 1). Herein, we report that allyl cyanide (1a) serves as a versatile C4 carbon pronucleophile to allow enantioselective access to α,β-unsaturated δ-valerolactones [Eq. (1)].