title: An efficient and general route to gem-difluoromethylenated alpha,beta-unsaturated delta-lactones: high enantioselective synthesis of gem-difluoromethylenated goniothalamins.
abstract: An efficient and general strategy to gem-difluoromethylenated alpha,beta-unsaturated delta-lactones in high yields from various aldehydes (including aliphatic, aromatic, alpha,beta-unsaturated, and sterically hindered aldehydes) has been developed. This methodology was successfully applied for the preparation of two enantiomers of gem-difluoromethylenated goniothalamins (S)-1 and (R)-1. gem-Difluoropropargylation of cinnamaldehyde followed by the resolution of resulting homopropargylic alcohols mediated by lipase from Pseudomonas (AK) gave alcohols (R)-6 and (S)-6. Selective hydrogenation of the triple bond of (S)-6 and (R)-6 to double bond with Lindlar catalyst in the presence of quinoline afforded the expected product (S)-8 and (R)-8, respectively. Deprotection of (S)-8 and (R)-8 followed by oxidation of the resulting 1,5-diols with catalytic 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and excess bis-acetoxyiodobenzene (BAIB) provided the target molecules gem-difluoromethylenated goniothalamins (S)-1 and (R)-1 in high yields, respectively.
authors.affiliation: Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 354 Fenglin Lu, Shanghai 200032, China.
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: You
authors.forename: Zhong-Xing
authors.initials: ZX
authors.lastname: Jiang
authors.forename: Bing-Lin
authors.initials: BL
authors.lastname: Wang
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Qing
mesh_terms: D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D005663:Furans; D006845:Hydrocarbons, Fluorinated; D007783:Lactones; C055449:goniothalamicin