A Concise Enantioselective Total Synthesis of (−)‐Virosaine A. Issue 36 (27th July 2017)

• Record Type: Journal Article
• Authors: Hughes, Jonathan M. E.; Gleason, James L.
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 36(2017)
• Page Start: 10830
• Page End: 10834
• Publication Date: 2017-07-27
• Subjects: alkaloids -- cascade reactions -- directed lithiation -- total synthesis -- virosaine A; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201706273
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 of1 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 of1 . Abstract : 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.