title: Evaluating the thermal vinylcyclopropane rearrangement (VCPR) as a practical method for the synthesis of difluorinated cyclopentenes: experimental and computational studies of rearrangement stereospecificity.
abstract: Vinyl cyclopropane rearrangement (VCPR) has been utilised to synthesise a difluorinated cyclopentene stereospecifically and under mild thermal conditions. Difluorocyclopropanation chemistry afforded ethyl 3-(1'(2'2'-difluoro-3'-phenyl)cyclopropyl) propenoate as all four stereoisomers (18a, 18b, 22a, 22b) (all racemic). The trans-E isomer (18a), prepared in 70 % yield over three steps, underwent near quantitative VCPR to difluorocyclopentene 23 (99 %). Rearrangements were monitored by (19) F NMR (100-180 °C). While cis/trans cyclopropane stereoisomerisation was facile, favouring trans-isomers by a modest margin, no E/Z alkene isomerisation was observed even at higher temperatures. Neither cis nor trans Z-alkenoates underwent VCPR, even up to much higher temperatures (180 °C). The cis-cyclopropanes underwent [3,3]-rearrangement to afford benzocycloheptadiene species. The reaction stereospecificity was explored by using electronic structure calculations, and UB3LYP/6-31G* methodology allowed the energy barriers for cyclopropane stereoisomerisation, diastereoisomeric VCPR and [3,3]-rearrangement to be ranked in agreement with experiment.
authors.affiliation: WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL (UK), Fax: (+44) 141-548-4822.
authors.forename: David
authors.initials: D
authors.lastname: Orr
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Percy
authors.forename: Tell
authors.initials: T
authors.lastname: Tuttle
authors.forename: Alan R
authors.initials: AR
authors.lastname: Kennedy
authors.forename: Zoë A
authors.initials: ZA
authors.lastname: Harrison
mesh_terms: D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry; D007536:Isomerism; D013237:Stereoisomerism; D013816:Thermodynamics; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D003517:Cyclopentanes; D006845:Hydrocarbons, Fluorinated; D014753:Vinyl Compounds
keywords: activation parameters; density functional calculations; difluorocyclopentene; rearrangements; stereoselectivity