An efficient, palladium-catalyzed, enantioselective synthesis of (2 R )-3-butene-1,2-diol and its use in highly selective Heck reactions

doi:10.1073/pnas.0307047101

An efficient, palladium-catalyzed, enantioselective synthesis of (2R)-3-butene-1,2-diol and its use in highly selective Heck reactions

Dowpharma, Chirotech Technology Ltd., A Subsidiary of the Dow Chemical Company, Cambridge Science Park, Milton Road, Cambridge CB4 0WG, United Kingdom

Edited by Barry M. Trost, Stanford University, Stanford, CA, and approved December 12, 2003 (received for review October 30, 2003)

Abstract

A robust and scalable procedure for the palladium-catalyzed dynamic kinetic asymmetric transformation of 3,4-epoxy-1-butene into (2R)-3-butene-1,2-diol with water as the cosolvent is reported. Examination of the effects of solvent and temperature led to the identification of conditions that permitted use of 0.025 mol % catalyst, providing (2R)-3-butene-1,2-diol in 84% isolated yield and 85% enantiomeric excess. Subsequent Heck reactions with a diverse range of coupling partners are described and the influence of their electronic nature on maintaining the enantiopurity of the diol is discussed.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: gmeek{at}dow.com.
↵ * Present address: H33-S-018, GlaxoSmithKline, New Frontiers Science Park (North), Third Avenue, Harlow, Essex CM19 5AW, United Kingdom.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: Pd₂dba₃·CHCl₃, tris(dibenzylideneacetone)dipalladium(0)·chloroform adduct; THF, tetrahydrofuran; MTBE, methyl tert-butyl ether; P(o-tol)₃, tri-o-tolylphosphine; ee, enantiomeric excess.