title: Cascade Michael addition/cycloketalization of cyclic 1,3-dicarbonyl compounds: important role of the tethered alcohol of α,β-unsaturated carbonyl compounds on reaction rate and regioselectivity.
abstract: Reactions of α,β-unsaturated aldehydes and cyclic 1,3-dicarbonyl compounds proceed primarily by cascade Knoevenagel condensation/six-π-electron electrocyclization (K6EC, formal [3 + 3] cycloaddition), while α,β-unsaturated ketones usually react with cyclic 1,3-dicarbonyl compounds in a 1,4-addition manner. This paper discloses our findings that under acidic conditions, α,β-unsaturated carbonyl compounds (ketones and aldehydes) with a tethered alcohol react with cyclic 1,3-dicarbonyl compounds in a highly regioselective 1,4-addition fashion via in situ generation of a hypothetical α-methylene cyclic oxonium ion as the reactive Michael acceptor. Our studies uncovered the important effect of the tethered alcohol on the reaction rate and/or efficiency and some new mechanistic aspects of the cascade Michael addition/cycloketalization. Finally, the substrate scope was examined, and 43 analogues of penicipyrone and tenuipyrone were prepared in good to excellent yields.
authors.affiliation: Department of Chemistry, The Hong Kong University of Science and Technology , Clearwater Bay, Kowloon, Hong Kong, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Yao
authors.forename: Liyan
authors.initials: L
authors.lastname: Song
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Tong
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D003500:Cyclization; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D009861:Onium Compounds / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000438:Alcohols; D000447:Aldehydes; D007659:Ketones; D009861:Onium Compounds; D011753:Pyrones