Stereodivergent Attached-Ring Synthesis via Non-Covalent Interactions: A Short Formal Synthesis of Merrilactone A

Angew Chem Int Ed Engl. 2022 Jan 17;61(3):e202114514. doi: 10.1002/anie.202114514. Epub 2021 Dec 9.

Abstract

A strategy to control the diastereoselectivity of bond formation at a prochiral attached-ring bridgehead is reported. An unusual stereodivergent Michael reaction relies on basic vs. Lewis acidic conditions and non-covalent interactions to control re- vs. si- facial selectivity en route to fully substituted attached-rings. This divergency reflects differential engagement of one rotational isomer of the attached-ring system. The successful synthesis of an erythro subtarget diastereomer ultimately leads to a short formal synthesis of merrilactone A.

Keywords: Michael addition; attached-ring; diastereoselectivity; natural products; synthesis design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cyclization
  • Lactones / chemical synthesis*
  • Lactones / chemistry
  • Molecular Structure
  • Sesquiterpenes / chemical synthesis*
  • Sesquiterpenes / chemistry
  • Stereoisomerism

Substances

  • Lactones
  • Sesquiterpenes
  • merrilactone A