The Pauson-Khand Reaction in Triquinane Synthesis: Approaches to Pentalenene, Pentalenic Acid, and Silphinene

Article abstract of DOI:10.1021/jo00051a034

Substituted pentynylcyclopentene precursors for the synthesis of pentalenene, pentalenic acid, and silphinene by intramolecular Pauson-Khand cycloaddition reaction have been prepared from 2-methylcyclopentanone via 5-methylcyclopentenyllithium.Conjugate addition of the latter to BHT methacrylate followed by methylation were the key steps in enyne synthesis.Reaction of 4,4-dimethyl-5-(5-methylcyclopentenyl)-1-pentyne with Co2(CO)8 produces two diastereomeric triquinane enones in an overall yield of 51percent, with the exo-9-methyl isomer predominating by ratio of 8:1.This material was converted into pentalenene in two steps.Pauson-Khand reaction of the TBDMS ether of 4,4-dimethyl-5-(5-methylcyclopentenyl)-1-pentyn-3-ol proceeds in 33percent yield.Three of the four possible stereoisomeric products are formed, with two of them, making up to ca. 80percent of the product mixture, possessing the necessary exo-methyl stereochemistry at C-9 for further elaboration into pentalenic acid.A formal synthesis of the latter was completed by reduction of one of the enone isomers into a ketone which had previously been carried on to the natural product.Pd(0)-catalyzed coupling of 1-iodo-5-methylcyclopentene to 1-(trimethylsilyl)-1,4-pentadiyne and reduction over Lindlar's catalyst allowed efficient access to (Z)-1-(5-methylcyclopentenyl)-1-penten-4-yne, but the latter could not be induced to undergo Pauson-Khand cyclization, thus foiling a planned approach to silphinene.