N-Heterocyclic Carbene-Catalyzed Aza-Michael-Mannich-Lactamization Cascade for the Enantioselective Synthesis of Pyrazoloquinolin-3-ones

Org Lett. 2023 Jan 13;25(1):220-225. doi: 10.1021/acs.orglett.2c04070. Epub 2023 Jan 3.

Abstract

The enantioselective synthesis of functionalized pyrazoloquinolin-3-ones via N-heterocyclic carbene-catalyzed cascade reaction of α-bromoenals with 2-aminoaryl N-tosyl hydrazones is reported. The in situ-generated α,β-unsaturated acylazoliums underwent an aza-Michael-Mannich-lactamization sequence to afford the tricyclic products bearing three contiguous stereocenters, including a sterically demanding quaternary stereocenter with high enantioselectivity. The unprotected amine-triggered aza-Michael pathway over the competing amidation pathway is noteworthy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines*
  • Catalysis
  • Methane*
  • Stereoisomerism

Substances

  • carbene
  • Amines
  • Methane