Synthesis of Polycyclic Compounds Employing Palladium-catalyzed Cycloalkenylation

Abstract

In 1979, Ito and Saegusa et al. discovered that the corresponding silyl enol ethers of the alkenyl ketones produce the cyclic β, γ-unsaturated ketones in the presence of palladium acetate. In addition, Kende et al. and Shibasaki et al. have individually investigated the reaction mechanism of cycloalkenylation process and the application to bioactive natural product syntheses, e.g. quadrone, phyllocladene, and capnellene derivatives.During the course of our investigations toward total syntheses of terpenoids, such as hirsutene and stemodin, we also reported synthetic routes to the bicyclo [3.3.0] octane ring system and decalin unit using Pd (II) -promoted cycloalkenylations. However, the process employing stoichiometric amounts of Pd (OAc) 2 suffers from low yields on large scale due probably to tarry Pd (0) species produced by reductive elimination. This is a serious limitation in the application of cycloalkenylation involving Pd (II).To solve this problem, we developed a novel palladium-catalyzed cycloalkenylation by applying Larock's conditions. On top of that, the methodology was successfully adapted for the synthesis of the bicyclo [3.2.1] octanes, bicyclo [3.3.0] octanes, benzo-fused bicyclo [3.3.0] octanes, and the tandem cycloalkenylation process.In this review, we would like to give a comprehensive coverage of the above-described aspects of palladium-catalyzed cycloalkenylations.