Asymmetric Phase-Transfer Catalytic aza-Michael Addition to Cyclic Enone: Highly Enantioselective and Diastereoselective Synthesis of Cyclic 1,3-Aminoalcohols

Org Lett. 2022 Mar 4;24(8):1647-1651. doi: 10.1021/acs.orglett.2c00192. Epub 2022 Feb 17.

Abstract

The highly enantioselective aza-Michael reaction of tert-butyl β-naphthylmethoxycarbamate to cyclic enones has been accomplished by using a new cinchona alkaloid derived C(9)-urea ammonium catalyst under phase-transfer catalysis conditions with up to 98% ee at 0 °C. The resulting aza-Michael adducts can be converted to versatile intermediates by selective deprotection and the cyclic 1,3-aminoalcohols by diastereoselective reduction with up to 32:1, which have been widely used as important pharmacophores in pharmaceutical development.

Publication types

  • Research Support, Non-U.S. Gov't