Evaluating the thermal vinylcyclopropane rearrangement (VCPR) as a practical method for the synthesis of difluorinated cyclopentenes : experimental and computational studies of rearrangement stereospecificity

Orr, David and Percy, Jonathan and Tuttle, Tell and Kennedy, Alan and Harrison, Zoe Alicia (2014) Evaluating the thermal vinylcyclopropane rearrangement (VCPR) as a practical method for the synthesis of difluorinated cyclopentenes : experimental and computational studies of rearrangement stereospecificity. Chemistry - A European Journal, 20 (44). 14305–14316. ISSN 0947-6539 (https://doi.org/10.1002/chem.201403737)

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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). Trans-E isomer (18a), prepared in 70% yield over three steps, underwent near quantitative VCPR to difluorocyclopentene 23 (99%). Rearrangements were followed by 19F 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 oC). Cis-cyclopropanes underwent [3,3]-rearrangement to afford benzocycloheptadiene species. The reaction stereospecificity was explored 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.

ORCID iDs

Orr, David, Percy, Jonathan ORCID logoORCID: https://orcid.org/0000-0001-8636-2704, Tuttle, Tell, Kennedy, Alan ORCID logoORCID: https://orcid.org/0000-0003-3652-6015 and Harrison, Zoe Alicia;
CORE (COnnecting REpositories)