Enantioselective γ-Addition of Pyrazole and Imidazole Heterocycles to Allenoates Catalyzed by Chiral Phosphine

Chiral phosphines were found to catalyze the enantioselective asymmetric gamma-addition of heteroaromatic compounds to allenoates in good yields with high enantiomeric ratios and regioselectivity in the presence of (S)-BINOL. Both pyrazole and imidazole could be employed in this process. The synthetic value of these gamma-addition products was demonstrated by the preparation of biologically relevant molecules and structural scaffolds. Remarkably, the synthetic utility of this strategy was demonstrated through a two-step synthesis of a Janus kinase (JAK) inhibitor.