Preparation of (5R)-4,8-dimethylbicyclo[3.3.0]oct-1(8),3-dien-2-one from (-)-limonene oxide : a novel intermediate to the synthesis of 4-5-5 fused tricarbocyclic core present in terpenic natural products

Abstract

Este trabalho refere-se à síntese enantiosseletiva da dienona (5R)-4,8-dimethylbicyclo[3.3.0]oct- 1(8),3-dien-2-one. Este intermediário, pode ser reconhecido como um bloco de construção versátil para a síntese de uma grande variedade de compostos com esqueleto biciclo[3.3.0]octano. A estratégia sintética empregada aqui faz uso da reatividade invertida de um precursor cianoidrina TMS-éter, como equivalente de ânion acila, para promover uma reação de alquilação intramolecular. A síntese formal do (-)-kelsoeno foi realizada pela preparação do intermediário avançado (1R,5S,8R)-4,8- dimethylbicyclo[3.3.0]oct-3-en-2-one, a partir da hidrogenação seletiva do composto intitulado (5R)- 4,8-dimethylbicyclo[3.3.0]oct-1(8),3-dien-2-one.

This paper describes the conversion of the readily available (-)-limonene oxide to the new (5R)- 4,8-dimethylbicyclo[3.3.0]oct-1(8),3-dien-2-one. This compound holds the prospect of serving as a useful chiral building block or intermediate to prepare a variety of compounds having a bicyclo[3.3.0]octane framework. The synthetic strategy made use of the umpolung reactivity of cyanohydrin TMS ether, as an acyl anion equivalent, in order to promote intramolecular alkylation. The formal synthesis of (-)-kelsoene was achieved by preparing a known advanced intermediate (1R,5S,8R)-4,8-dimethylbicyclo[3.3.0]oct-3-en-2-one via selective hydrogenation of the named compound (5R)-4,8-dimethylbicyclo[3.3.0]oct-1(8),3-dien-2-one.