A Concise Enantioselective Total Synthesis of (−)‐Virosaine A

The total synthesis of (−)‐virosaine A (1) was achieved in ten steps starting from furan and 2‐bromoacrolein. A one‐pot Diels–Alder cycloaddition/organolithium addition initiated an efficient sequence to access a key oxime/epoxide intermediate. Heating this intermediate in acetic acid resulted in an intramolecular epoxide opening/nitrone [3+2] cycloaddition cascade to construct the caged core of 1 in a single step. Several methods of C−H functionalization were assessed on the cascade product, and ultimately, a directed lithiation/bromination effected selective C14 functionalization, enabling the synthesis of 1. Not too late: The core of virosaine A was prepared in five short steps by a cycloaddition/organolithium addition and a nitrone formation/cycloaddition cascade. Late‐stage selective functionalization of an unactivated C−H group by directed lithiation enabled conversion of the shown key intermediate into the natural product.