title: Copper-Catalyzed Double Additions and Radical Cyclization Cascades in the Re-Engineering of the Antibacterial Pleuromutilin.
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.
authors.affiliation: School of Chemistry University of Manchester, Oxford Rd, Manchester, M13 9PL (UK).
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Ruscoe
authors.affiliation: School of Chemistry University of Manchester, Oxford Rd, Manchester, M13 9PL (UK).
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Fazakerley
authors.affiliation: School of Chemistry University of Manchester, Oxford Rd, Manchester, M13 9PL (UK).
authors.forename: Huanming
authors.initials: H
authors.lastname: Huang
authors.affiliation: School of Chemistry University of Manchester, Oxford Rd, Manchester, M13 9PL (UK).
authors.forename: Sabine
authors.initials: S
authors.lastname: Flitsch
authors.affiliation: School of Chemistry University of Manchester, Oxford Rd, Manchester, M13 9PL (UK). david.j.procter@manchester.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Procter
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D001688:Biological Products; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000737:chemistry; D053138:Cyclohexenes / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D012493:Samarium / Q000737:chemistry*; D013237:Stereoisomerism; D000097567:Pleuromutilins
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D003300:Copper; D003512:Cyclohexanones; D053138:Cyclohexenes; D004224:Diterpenes; D028581:Lanthanoid Series Elements; D011083:Polycyclic Compounds; D012493:Samarium; D000097567:Pleuromutilins; C000608458:beta-chlorocyclohexenone
keywords: cyclization; domino reactions; electron-transfer; radical reactions; samarium