Catalytic C(sp3)-H Alkylation via an Iron Carbene Intermediate

J Am Chem Soc. 2017 Oct 4;139(39):13624-13627. doi: 10.1021/jacs.7b07602. Epub 2017 Sep 22.

Abstract

The catalytic transformation of a C(sp3)-H bond to a C(sp3)-C bond via an iron carbene intermediate represents a long-standing challenge. Despite the success of enzymatic and small molecule iron catalysts mediating challenging C(sp3)-H oxidations and aminations via high-valent iron oxos and nitrenes, C(sp3)-H alkylations via isoelectronic iron carbene intermediates have thus far been unsuccessful. Iron carbenes have been inert, or shown to favor olefin cyclopropanation and heteroatom-hydrogen insertion. Herein we report an iron phthalocyanine-catalyzed alkylation of allylic and benzylic C(sp3)-H bonds. Mechanistic investigations support that an electrophilic iron carbene mediates homolytic C-H cleavage and rebounds from the resulting organoiron intermediate to form the C-C bond; both steps are tunable via catalyst modifications. These studies suggest that for iron carbenes, distinct from other late metal carbenes, C-H cleavage is partially rate-determining and must be promoted to effect reactivity.

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

  • Alkylation
  • Catalysis
  • Iron / chemistry*
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Molecular Structure
  • Stereoisomerism

Substances

  • carbene
  • Iron
  • Methane