General method of synthesis of cyclopentanoid terpenic acids. Stereocontrolled total syntheses of (±)-isocomenic acid and (±)-epiisocomenic acid

Abstract

(4β,8α)-lα,2,4β-Trimethyl-9α-caboxytricyclo[6.3.0.0] undec-2-ene (1, isocomenic acid) and (4β, 8α)-lα,2,4β-trimethyl-9β-carboxytricyclo[6.3.0.0] undec-2-ene (28, epiisocomenic acid) were prepared in 10 steps from ester 13. The internal cyclopropanation of exocyclic acrylates and the subsequent vinylcyclopropane-cyclopentene rearrangement were used in an efficient synthesis of a key intermediate, triquinane 23, containing all of the contiguous quaternary centers. The utilization of abnormal Reformatsky reaction of 4-bromocrotonates with keto esters served in the preparation of important precursors to the cyclopentene annulation sequence, the lactone 15, and the dienic acid 19. Hydrogenation of 23 produced the keto ester 25a, which was converted in three steps to either 1 or 28 with complete control of stereochemistry. Carbon-13 data are reported for all intermediates. A total of eight natural products are accessible in a stereocontrolled fashion from keto ester 25a. The generality of this method is thus addressed in the context of system-oriented design of synthesis of cyclopentanoid terpenes.