Asymmetric total synthetis of (+)-pentalenene

Abstract

Pentalenene, a sesquiterpene with tricycle[6.3.0.0]undecane core structure was isolated from Streptomyces griseochromogenes by Seto and Yonehara in 1980. A great attention has been drawn to this natural product since it is the representative angular triquinane natural product to test newly developed synthetic methodologies and is the biosynthetic precursor of pentalenolactone, an antibiotic metabolites, produced by several Streptomyces species. Only few strategies that assembled two or more rings in one-step were reported

thermolytic rearrangement, metal-catalyzed transformation, squarate ester cascade, tandem radical cyclization, arene olefin photocycloaddition, and intramolecular Pauson-Khand reaction. A stereoselective total synthesis of (+)-pentalenene was achieved through the tandem cycloaddition reaction of the allenyl diazo substrate prepared from (+)-citronellal. The initial intramolecular [2+3] cycloaddition reaction between the diazo functionality and the allenyl group produced the trimethylenemethane (TMM) intermediate after immediate loss of nitrogen molecule from the cycloaddition intermediate. Subsequent [2+3] cycloaddition of the TMM with olefin produced the angularly fused triquinane structure stereoselectively. The readily available epoxy sulfone provides controlled access to the four-membered ring to seven-membered ring via either formal exo or endo opening of the derived carbanion, respectively. The mode of ring opening in these compounds is controlled by the choice of reagent, as the use of lithium amide base effect exo ring opening of the epoxide, while the use of organomangesium bases affords the product from formal endo ring opening. The anomeric sulfone functionality present in oxacycles can also be further functionalized for the synthesis of target molecules. This functionalization of sulfone moiety has been less studied due to its less reactivity compared to other leaving group. Stereoselective C-glycosylation and O-glycosylation have been investigated, which approaches could be applied to the synthesis of phamaceuticals, and naturally occurring compounds.