title: Catalytic Asymmetric Synthesis of Ketene Heterodimer β-Lactones: Scope and Limitations.
abstract: In this article we describe extensive studies of the catalytic asymmetric heterodimerization of ketenes to give ketene heterodimer β-lactones. The optimal catalytic system was determined to be a cinchona alkaloid derivative (TMS-quinine or Me-quinidine). The desired ketene heterodimer β-lactones were obtained in good to excellent yields (up to 90%), with excellent levels of enantioselectivity (≥90% ee for 33 Z and E isomer examples), good to excellent (Z)-olefin isomer selectivity (≥90:10 for 20 examples), and excellent regioselectivity (only one regioisomer formed). Full details of catalyst development studies, catalyst loading investigations, substrate scope exploration, protocol innovations (including double in situ ketene generation for 7 examples), and an application to a cinnabaramide A intermediate are described. The addition of lithium perchlorate (1-2 equiv) as an additive to the alkaloid catalyst system was found to favor formation of the E isomer of the ketene heterodimer. Ten examples were formed with moderate to excellent (E)-olefin isomer selectivity (74:25 to 97:3) and with excellent enantioselectivity (84-98% ee).
authors.affiliation: Department of Chemistry, Oakland University , 2200 North Squirrel Road, Rochester, Michigan 48309-4477, United States.
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Oakland University , 2200 North Squirrel Road, Rochester, Michigan 48309-4477, United States.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Ibrahim
authors.affiliation: Department of Chemistry, Oakland University , 2200 North Squirrel Road, Rochester, Michigan 48309-4477, United States.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Peraino
authors.affiliation: Department of Chemistry, Oakland University , 2200 North Squirrel Road, Rochester, Michigan 48309-4477, United States.
authors.forename: Divya
authors.initials: D
authors.lastname: Nalla
authors.affiliation: Department of Chemistry, Oakland University , 2200 North Squirrel Road, Rochester, Michigan 48309-4477, United States.
authors.forename: Mukulesh
authors.initials: M
authors.lastname: Mondal
authors.affiliation: Department of Chemistry, Oakland University , 2200 North Squirrel Road, Rochester, Michigan 48309-4477, United States.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Van Raaphorst
authors.affiliation: Department of Chemistry, Oakland University , 2200 North Squirrel Road, Rochester, Michigan 48309-4477, United States.
authors.forename: Nessan J
authors.initials: NJ
authors.lastname: Kerrigan
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002384:Catalysis; D019281:Dimerization; D005030:Ethylenes / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D013058:Mass Spectrometry; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
chemical_list: D005030:Ethylenes; D007659:Ketones; D007783:Lactones; C008223:ketene