Premium
Evaluating the Thermal Vinylcyclopropane Rearrangement (VCPR) as a Practical Method for the Synthesis of Difluorinated Cyclopentenes: Experimental and Computational Studies of Rearrangement Stereospecificity
Author(s) -
Orr David,
Percy Jonathan M.,
Tuttle Tell,
Kennedy Alan R.,
Harrison Zoë A.
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201403737
Subject(s) - cyclopropane , cyclopentene , stereospecificity , isomerization , chemistry , alkene , yield (engineering) , computational chemistry , cis–trans isomerism , medicinal chemistry , stereochemistry , organic chemistry , ring (chemistry) , catalysis , materials science , metallurgy
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.