Catalytic Hydrogenation with Frustrated Lewis Pairs: Selectivity Achieved by Size-Exclusion Design of Lewis Acids

Catalytic hydrogenation that utilizes frustrated Lewis pair (FLP) catalysts is a subject of growing interest because such catalysts offer a unique opportunity for the development of transition-metal-free hydrogenations. The aim of our recent efforts is to further increase the functional-group tolerance and chemoselectivity of FLP catalysts by means of size-exclusion catalyst design. Given that hydrogen molecule is the smallest molecule, our modified Lewis acids feature a highly shielded boron center that still allows the cleavage of the hydrogen but avoids undesirable FLP reactivity by simple physical constraint. As a result, greater latitude in substrate scope can be achieved, as exemplified by the chemoselective reduction of alpha,beta-unsaturated imines, ketones, and quinolines. In addition to synthetic aspects, detailed NMR spectroscopic, DFT, and H-2 isotopic labeling studies were performed to gain further mechanistic insight into FLP hydrogenation.