Lipase-catalyzed domino kinetic resolution/intramolecular Diels-Alder reaction: one-pot synthesis of optically active 7-oxabicyclo[2.2.1]heptenes from furfuryl alcohols and beta-substituted acrylic acids

Chemistry. 2002 Sep 16;8(18):4255-64. doi: 10.1002/1521-3765(20020916)8:18<4255::AID-CHEM4255>3.0.CO;2-6.

Abstract

The first lipase-catalyzed domino reaction is described in which the acyl moiety formed during the enzymatic kinetic resolution of furfuryl alcohols (+/-)-3 with a 1-ethoxyvinyl ester 2 was utilized as a part of the constituent structure for the subsequent Diels-Alder reaction. The preparation of ester 2 from carboxylic acid 1 and the subsequent domino reaction were carried out in a one-pot reaction. Therefore, this procedure provides a convenient preparation of the optically active 7-oxabicyclo[2.2.1]heptene derivatives 5, which has five chiral, non-racemic carbon centers, from achiral 1 and racemic 3. The overall efficiency of this process was dependent on the substituent at the C-3 position of 3, and the use of the 3-methylfurfuryl derivatives, (+/-)-3 b and (+/-)-3 f, exclusively produced diastereoselectivity with excellent enantioselectivity to give (2R)-syn-5 (91->/=99 % ee) and (S)-3 (96->/=99 % ee). Similar procedures starting from the 3-bromofurfuryl alcohols (+/-)-3 h-j provided the cycloadducts (2R)-syn-5 j-q (93->/=99 % ee), in which the bromo group was utilized for the installation of bulky substituents to the 7-oxabicycloheptene core.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylates / chemistry*
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry*
  • Catalysis
  • Esters / chemistry
  • Furans / chemistry*
  • Kinetics
  • Lipase / metabolism*
  • Pseudomonas / enzymology
  • Stereoisomerism

Substances

  • Acrylates
  • Bridged Bicyclo Compounds
  • Esters
  • Furans
  • furfuryl alcohol
  • Lipase
  • acrylic acid