Total synthesis of (+)-asteriscanolide: further exploration of the rhodium(I)-catalyzed [(5+2)+1] reaction of ene-vinylcyclopropanes and CO.
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.
Beijing National Laboratory for Molecular Sciences (BNLMS), College of Chemistry, Peking University, Beijing 100871, China.
Yong
Y
Liang
Xing
X
Jiang
Xu-Fei
XF
Fu
Siyu
S
Ye
Tao
T
Wang
Jie
J
Yuan
Yuanyuan
Y
Wang
Zhi-Xiang
ZX
Yu
D002248:Carbon Monoxide / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D003521:Cyclopropanes / Q000737:chemistry*; D015394:Molecular Structure; D012238:Rhodium / Q000737:chemistry*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D003521:Cyclopropanes; D012717:Sesquiterpenes; C449084:asteriscanolide; D002248:Carbon Monoxide; D012238:Rhodium