Catalytic enantioselective alkylation of substituted dioxanone enol ethers: ready access to Calpha-tetrasubstituted hydroxyketones, acids, and esters

Angew Chem Int Ed Engl. 2008;47(36):6873-6. doi: 10.1002/anie.200801424.

Abstract

The catalytic enantioselective formation of tetrasubstituted α-alkoxycarbonyl compounds is an ongoing challenge to synthetic chemists.[1] Fully-substituted α-hydroxyesters and acids comprise essential components of, and building blocks for, many bioactive natural products. These include quinic acid (1), cytotoxic leiodolide A (2),[2] and the anti-cancer agents in the harringtonine series (3af), whose activities depend dramatically on the presence and composition of an α-hydroxyester side-chain.[3] While many approaches to these important moieties exist,[4,5] we envisioned applying our recently developed palladium-catalyzed methods for the formation of enantioenriched all-carbon quaternary stereocenters in cyclic alkanones[6] to a general synthesis of C(α)-tetrasubstituted hydroxy carbonyl compounds.[7]

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / chemical synthesis
  • Alkylation
  • Biological Products / chemical synthesis*
  • Catalysis
  • Esters / chemical synthesis
  • Ethers / chemistry*
  • Ketones / chemical synthesis
  • Palladium / chemistry*

Substances

  • Acids
  • Biological Products
  • Esters
  • Ethers
  • Ketones
  • Palladium