Asymmetric Total Syntheses of Sarglamides A, C, and E

The asymmetric total syntheses of sarglamides A, C, and E in concise and protecting group free fashion is disclosed. Key steps involve an endo-selective Diels–Alder reaction to construct the bicyclo[2.2.2]nonane framework, a nucleophilic addition and an intramolecular aza-Michael addition to install the pyrrolidine ring, and a final cinnamoylation reaction. Sarglamide C is biomimetically transformed into E through a Brønsted acid mediated oxy-cyclization. Sarglamide D is also accessible from C based on Yue’s research. This work provides an efficient asymmetric approach to the syntheses of sarglamides and also provides insights into understand the plausible biogenetic pathway of these monoterpenoid–indolidinoid hybrid structures.