Asymmetric Synthesis of Remotely Chiral Naphthols and Naphthylamines via Naphthoquinone Methides

摘要

Quinone methides are well-establishedintermediates inasymmetricsynthesis. In contrast, their extended analogues with the carbonyland methide units distributed across two different rings have notbeen exploited in asymmetric synthesis. Herein, we achieved the firstasymmetric process involving such intermediates. Specifically, theuse of suitable chiral phosphoric acids enabled in situ generation of 2-naphthoquinone 8-methides and the correspondingaza counterparts for mild one-pot asymmetric nucleophilic addition.These processes provided rapid access to a wide range of previouslyless accessible remotely chiral naphthols and naphthylamines withboth high efficiency and excellent enantioselectivity. Control experimentand DFT calculations provided important insights into the reactionmechanism, which likely involves two phosphoric acid molecules inthe enantiodetermining transition states. This work serves as a proofof concept for the exploitation of new types of extended quinone methidesas versatile intermediates for asymmetric synthesis, thus providinga new platform for the efficient construction of remote benzylic stereogeniccenters of aromatic compounds.