A computational triage approach to the synthesis of novel difluorocyclopentenes and fluorinated cycloheptadienes using thermal rearrangements† †Electronic supplementary information (ESI) available: Computational methodology, Cartesian coordinates for intermediates and transition states, synthetic procedures and characterisation spectra for novel compounds and further discussion on points highlighted in the text. See DOI: 10.1039/c6sc01289b Click here for additional data file.

نویسندگان

  • David Orr
  • Jonathan M. Percy
  • Zoë A. Harrison
چکیده

Electronic structure calculations have been used for the effective triage of substituent effects on difluorinated vinylcyclopropane precursors and their ability to undergo vinyl cyclopropane rearrangements (VCPR). Groups which effectively stabilised radicals, specifically heteroarenes, were found to result in the lowest energy barriers. Ten novel precursors were synthesised to test the accuracy of computational predictions; the most reactive species which contained heteroarenes underwent thermal rearrangements at room temperature to afford novel difluorocyclopentenes and fluorinated benzocycloheptadienes through competing VCPR and [3,3]-rearrangement pathways, respectively. More controlled rearrangement of ethyl 3-(10(2020-difluoro-30-benzo[d][1,3]dioxol-5-yl)cyclopropyl)propenoate (22) allowed these competing pathways to be monitored at the same time and activation energies for both reactions were determined; Ea(VCPR) 1⁄4 (23.4 0.2) kcal mol 1 and Ea([3,3]) 1⁄4 (24.9 0.3) kcal mol . Comparing our calculated activation energies with these parameters showed that no single method stood out as the most accurate for predicting barrier heights; (U)M05-2X/6-31+G* methodology remained the best for VCPR but M06-2X/6-31G* was better for the [3,3]-rearrangement. The consistency observed with (U)B3LYP/6-31G* calculations meant that it came closest to a universal method for dealing with these systems. The developed computational design model correctly predicted the observed selectivity of rearrangement pathways for both our system and literature compounds.

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Department of Chemistry, Beijing Normal U [email protected]; [email protected]; Fax: Institut für Anorganische und Analyti Braunschweig, Hagenring 30, 38106 Brau tu-bs.de; Fax: +49-531-3915387; Tel: +49-53 † Electronic supplementary information ( all stationary points optimized at B3PW9 For ESI and crystallographic data in CI 10.1039/c5sc01684c ‡ These authors contributed equally to th Cite this: ...

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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016