title: Rapid assembly of complex cyclopentanes employing chiral, α,β-unsaturated acylammonium intermediates.
abstract: With the intention of improving synthetic efficiency, organic chemists have turned to bioinspired organocascade or domino processes that generate multiple bonds and stereocentres in a single operation. However, despite the great importance of substituted cyclopentanes, given their prevalence in complex natural products and pharmaceutical agents, the rapid, enantioselective assembly of these carbocycles lags behind cyclohexanes. Here, we describe a Michael-aldol-β-lactonization organocascade process for the synthesis of complex cyclopentanes utilizing chiral α,β-unsaturated acylammonium intermediates, readily generated by activation of commodity unsaturated acid chlorides with chiral isothiourea catalysts. This efficient methodology enables the construction of two C-C bonds, one C-O bond, two rings and up to three contiguous stereogenic centres delivering complex cyclopentanes with high levels of relative and absolute stereocontrol. Our results suggest that α,β-unsaturated acylammonium intermediates have broad utility for the design of organocascade and multicomponent processes, with the latter demonstrated by a Michael-Michael-aldol-β-lactonization.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Shirley
authors.forename: Khoi N
authors.initials: KN
authors.lastname: Van
authors.forename: Rae Lynn
authors.initials: RL
authors.lastname: McFarlin
authors.forename: Daniel
authors.identifier: 000000033805092X
authors.initials: D
authors.lastname: Romo
mesh_terms: D064751:Ammonium Compounds / Q000737:chemistry; D002384:Catalysis; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry*; D008314:Malonates / Q000737:chemistry; D008958:Models, Molecular; D013237:Stereoisomerism; D013890:Thiourea / Q000737:chemistry
chemical_list: D064751:Ammonium Compounds; D003517:Cyclopentanes; D008314:Malonates; C008375:mesoxalic acid; D013890:Thiourea