Catalytic Hydrothiolation: Counterion-Controlled Regioselectivity

J Am Chem Soc. 2019 Feb 20;141(7):3006-3013. doi: 10.1021/jacs.8b11395. Epub 2019 Feb 8.

Abstract

In this Article, we expand upon the catalytic hydrothiolation of 1,3-dienes to afford either allylic or homoallylic sulfides with high regiocontrol. Mechanistic studies support a pathway in which regioselectivity is dictated by the choice of counterion associated with the Rh center. Non-coordinating counterions, such as SbF6-, allow for η4-diene coordination to Rh complexes and result in allylic sulfides. In contrast, coordinating counterions, such as Cl-, favor neutral Rh complexes in which the diene binds η2 to afford homoallylic sulfides. We propose mechanisms that rationalize a fractional dependence on thiol for the 1,2-Markovnikov hydrothiolation while accounting for an inverse dependence on thiol in the 3,4- anti-Markovnikov pathway. Through the hydrothiolation of an essential oil (β-farnesene), we achieve the first enantioselective synthesis of (-)-agelasidine A.

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

  • Alkadienes / chemistry*
  • Catalysis
  • Coordination Complexes / chemistry
  • Guanidines / chemical synthesis
  • Isomerism
  • Kinetics
  • Models, Chemical
  • Rhodium / chemistry
  • Sesquiterpenes / chemistry
  • Sulfides / chemical synthesis*
  • Sulfones / chemical synthesis

Substances

  • Alkadienes
  • Coordination Complexes
  • Guanidines
  • Sesquiterpenes
  • Sulfides
  • Sulfones
  • agelasidine A
  • beta-farnesene
  • Rhodium