Total Synthesis of (+)-Xiamycin G via Acetanilide Assisted Two-Fold Csp2-H Functionalization

Abstract

The first asymmetric total synthesis of the structurally unique naturally occurring indolosesquiterpene alkaloid, xiamycin G (1b) has been accomplished via a two-fold Csp2-H functionalizations. The aniline directed Csp2-H functionalization to afford functionalized trifluoro N-acyl phenol derivative 15, whereas the second Csp2-H functionalization helped to craft pentacyclic core 23. Importantly, functionalized tricycle 15 sharing four contiguous stereogenic centers was confirmed through X-ray analysis, thereby unequivocal proof of all stereogenic centers present in indolosesquiterpene alkaloid 1b. Overall, this approach testament the application of a two-fold Csp2-H functionalization in complex alkaloid synthesis.