A bio-inspired cascade and a late-stage directed sp3 CH lithiation enables a concise total synthesis of (−)-virosaine A. Issue 8 (22nd February 2018)

• Record Type: Journal Article
• Authors: Hughes, Jonathan M.E.; Gleason, James L.
• Is Part Of: Tetrahedron. Volume 74:Issue 8(2018)
• Page Start: 759
• Page End: 768
• Publication Date: 2018-02-22
• Subjects: Alkaloids -- Cascade reactions -- Total synthesis -- Directed lithiation -- Cycloaddition; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2017.12.026
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The asymmetric total synthesis of (−)-virosaine A was achieved in 9% overall yield from commercially/readily available starting materials. Inspired by an intriguing biosynthetic proposal, a novel cascade reaction sequence was developed to efficiently construct the caged polycyclic core of virosaine A. The pivotal cascade precursor was readily available in enantiopure form via a robust route that featured an enantioselective one-pot Diels-Alder cycloaddition/organolithium addition. Several contemporary methods of CH functionalization were applied to the cascade product and yielded a diverse set of novel complex polycycles. Ultimately, a combination of NMR and computational analyses laid the groundwork for a successful directed lithiation strategy to selectively functionalize the caged core and complete the total synthesis of virosaine A. Graphical abstract: