Copper‐Catalyzed Double Additions and Radical Cyclization Cascades in the Re‐Engineering of the Antibacterial Pleuromutilin. Issue 1 (26th November 2015)

• Record Type: Journal Article
• Authors: Ruscoe, Rebecca E.; Fazakerley, Neal J.; Huang, Huanming; Flitsch, Sabine; Procter, David J.
• Is Part Of: Chemistry. Volume 22:Issue 1(2016)
• Page Start: 116
• Page End: 119
• Publication Date: 2015-11-26
• Subjects: cyclization -- domino reactions -- electron‐transfer -- radical reactions -- samarium; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201504343
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A general synthetic sequence involving simply prepared starting materials provides rapid access to diverse, novel tricyclic architectures inspired by pleuromutilin. Sm II ‐mediated radical cyclization cascades of dialdehydes, prepared using a new, one‐pot, copper‐catalyzed double organomagnesium addition to β‐chlorocyclohexenone, proceed with complete sequence selectivity and typically with high diastereocontrol to give analogues of the target core. Our expedient approach (ca. 7 steps) allows non‐traditional, de novo synthetic access to analogues of the important antibacterial that can′t be prepared from the natural product by semisynthesis. Abstract : Cascade processes : A general synthetic sequence involving simply prepared starting materials provides rapid access to diverse, novel tricyclic architectures inspired by pleuromutilin. Sm II ‐mediated radical cyclization cascades of dialdehydes, prepared using a new, one‐pot, copper‐catalyzed double organomagnesium addition to β‐chlorocyclohexenone, provide rapid access to novel analogues of the core of the important antibacterial (see scheme).