Total synthesis of (+)-asteriscanolide: further exploration of the rhodium(I)-catalyzed [(5+2)+1] reaction of ene-vinylcyclopropanes and CO

• Published in: Chemistry, an Asian journal Vol. 7; no. 3; p. 593
• Main Authors: Liang, Yong, Jiang, Xing, Fu, Xu-Fei, Ye, Siyu, Wang, Tao, Yuan, Jie, Wang, Yuanyuan, Yu, Zhi-Xiang
• Format: Journal Article
• Language: English
• Published: Germany 05.03.2012
• Subjects: Carbon Monoxide - chemistry; Catalysis; Cyclization; Cyclopropanes - chemistry; Molecular Structure; Rhodium - chemistry; Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Stereoisomerism
• ISSN: 1861-471X
• DOI: 10.1002/asia.201100805

The total synthesis of (+)-asteriscanolide is reported. The synthetic route features two key reactions: 1) the rhodium(I)-catalyzed [(5+2)+1] cycloaddition of a chiral ene-vinylcyclopropane (ene-VCP) substrate to construct the [6.3.0] carbocyclic core with excellent asymmetric induction, and 2) an alkoxycarbonyl-radical cyclization that builds the bridging butyrolactone ring with high efficiency. Other features of this synthetic route include the catalytic asymmetric alkynylation of an aldehyde to synthesize the chiral ene-VCP substrate, a highly regioselective conversion of the [(5+2)+1] cycloadduct into its enol triflate, and the inversion of the inside-outside tricycle to the outside-outside structure by an ester-reduction/elimination to enol-ether/hydrogenation procedure. In addition, density functional theory (DFT) rationalization of the chiral induction of the [(5+2)+1] reaction and the diastereoselectivity of the radical annulation has been presented. Equally important is that we have also developed other routes to synthesize asteriscanolide using the rhodium(I)-catalyzed [(5+2)+1] cycloaddition as the key step. Even though these routes failed to achieve the total synthesis, these experiments gave further useful information about the scope of the [(5+2)+1] reaction and paved the way for its future application in synthesis.