Sustainable Pd(OAc)2 /Hydroquinone Cocatalyst System for Cis-Selective Dibenzoyloxylation of 1,3-Cyclohexadiene

Angew Chem Int Ed Engl. 2021 Oct 18;60(43):23182-23186. doi: 10.1002/anie.202108499. Epub 2021 Sep 17.

Abstract

The 1,4-diacyloxylation of 1,3-cyclohexadiene (CHD) affords valuable stereochemically defined scaffolds for natural product and pharmaceutical synthesis. Existing cis-selective diacyloxylation protocols require superstoichiometric quantities of benzoquinone (BQ) or MnO2 , which limit process sustainability and large-scale application. In this report, reaction development and mechanistic studies are described that overcome these limitations by pairing catalytic BQ with tert-butyl hydroperoxide as the stoichiometric oxidant. Catalytic quantities of bromide enable a switch from trans to cis diastereoselectivity. A catalyst with a 1:2 Pd:Br ratio supports high cis selectivity while retaining good rate and product yield. Further studies enable replacement of BQ with hydroquinone (HQ) as a source of cocatalyst, avoiding the handling of volatile and toxic BQ in large-scale applications.

Keywords: difunctionalization; homogeneous catalysis; oxidation; palladium; synthetic methods.

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

  • Acetates / chemistry*
  • Benzoates / chemical synthesis*
  • Catalysis
  • Cyclohexenes / chemical synthesis*
  • Hydroquinones / chemistry*
  • Organometallic Compounds / chemistry*
  • Palladium / chemistry
  • Stereoisomerism

Substances

  • Acetates
  • Benzoates
  • Cyclohexenes
  • Hydroquinones
  • Organometallic Compounds
  • palladium(II) acetate
  • Palladium
  • 1,3-cyclohexadiene