Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Hetero-triarylmethanes from Racemic Indolyl Alcohols.

Abstract

The direct enantioselective 1,4- and 1,8-arylations of 7-methide-7H-indoles and 6-methide-6H-indoles, respectively, generated in situ from diarylmethanols, with electron-rich arenes as nucleophiles, has been achieved in the presence of chiral phosphoric acids (CPAs). These two remote activation protocols provide an efficient approach for the construction of diverse hetero-triarylmethanes in high yields (up to 97 %) and with excellent enantioselectivities (up to 96 %). Mechanistically inspired experiments tentatively indicate that the catalytic enantioselective 1,4-addition as well as the formal SN 1 substitution could proceed efficiently in the similar catalytic systems. Furthermore, the modification of the catalytic system and diarylmethanol structure successfully deviates the reactivity toward a remote, highly enantioselective 1,8-arylation reaction. This flexible activation mode and novel reactivity of diarylmethanols expand the synthetic potential of chiral phosphoric acids.