An efficient and scalable one-pot double Michael addition-Dieckmann condensation for the synthesis of 4,4-disubstituted cyclohexane beta-keto esters

J Org Chem. 2007 Sep 14;72(19):7455-8. doi: 10.1021/jo071202h. Epub 2007 Aug 14.

Abstract

A simple, scalable, and efficient one-pot methodology for the synthesis of 4,4-disubstituted cyclohexane beta-keto esters from benzylic nitriles or esters and methyl acrylate promoted by potassium tert-butoxide is described. The process relies on a tandem double Michael addition-Dieckmann condensation reaction, which results in the formation of three discrete carbon-carbon bonds in a single pot, including a quaternary center. The method allows for the convenient and rapid synthesis of a variety of 4-aryl-4-cyano-2-carbomethoxycyclohexanone and 4-aryl-2,4-biscarbomethoxycyclohexanone building blocks for use in natural products synthesis and medicinal chemistry.

MeSH terms

  • Cyclohexanones / chemistry*
  • Esters / chemistry*

Substances

  • Cyclohexanones
  • Esters