Anti-selective [3+2] (Hetero)annulation of non-conjugated alkenes via directed nucleopalladation

Nat Commun. 2020 Dec 22;11(1):6432. doi: 10.1038/s41467-020-20182-4.

Abstract

2,3-Dihydrobenzofurans and indolines are common substructures in medicines and natural products. Herein, we describe a method that enables direct access to these core structures from non-conjugated alkenyl amides and ortho-iodoanilines/phenols. Under palladium(II) catalysis this [3 + 2] heteroannulation proceeds in an anti-selective fashion and tolerates a wide variety of functional groups. N-Acetyl, -tosyl, and -alkyl substituted ortho-iodoanilines, as well as free -NH2 variants, are all effective. Preliminary results with carbon-based coupling partners also demonstrate the viability of forming indane core structures using this approach. Experimental and computational studies on reactions with phenols support a mechanism involving turnover-limiting, endergonic directed oxypalladation, followed by intramolecular oxidative addition and reductive elimination.

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

  • Alkenes / chemistry*
  • Aniline Compounds / chemistry
  • Computer Simulation
  • Palladium / chemistry*
  • Phenols / chemistry
  • Thermodynamics

Substances

  • Alkenes
  • Aniline Compounds
  • Phenols
  • Palladium
  • aniline