Chiral phosphoric acid catalyzed aminative dearomatization of ?-naphthols/Michael addition sequence.

ABSTRACT: Asymmetric dearomatization reactions have recently emerged as a powerful tool for the rapid build-up of the molecular complexity. Chiral three-dimensional polycyclic molecules bearing contiguous stereogenic centers can be synthesized from readily available planar aromatic feedstocks. Here we report that an intermolecular asymmetric dearomatization reaction of ?-naphthols bearing a tethered nucleophile at the C4 position of the naphthol ring is achieved by a chiral phosphoric acid. The reaction proceeds via a highly chemo- and regioselective aminative dearomatization/Michael addition sequence, affording a wide array of functionalized cyclic ketones in good yields (up to 93%) with excellent enantioselectivity (up to >99% ee). The catalyst loading can be reduced to 0.1?mol%. Preliminary mechanistic investigations identify that the enantioselectivity is established in the dearomatization step, while the Michael addition is the rate-limiting step. A working model accounting for the origin of the stereochemistry is proposed based on DFT calculations.

SUBMITTER: Xia ZL 

PROVIDER: S-EPMC6637135 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature