- Comparison of Nucleofugalities in 1,2- and 1,3-Elimination Reactions
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Ranks ( nucleofugalities) of Br, Cl, OSO2C6H4Me, SO2Ph, SPh, and OPh as leaving groups in sulphonylactivated cyclopropane-forming eliminations have been determined; a rectilinear correlation between rank and the pKa of the conjugate acid of the leaving group is found in direct contrast with behaviour in alkene-forming elimination.
- Issari, Bahram,Stirling, Charles J. M.
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- Enantioselective Synthesis of Cyclopropanone Equivalents and Application to the Formation of Chiral β-Lactams
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Cyclopropanone derivatives have long been considered unsustainable synthetic intermediates because of their extreme strain and kinetic instability. Reported here is the enantioselective synthesis of 1-sulfonylcyclopropanols, as stable yet powerful equivalents of the corresponding cyclopropanone derivatives, by α-hydroxylation of sulfonylcyclopropanes using a bis(silyl) peroxide as the electrophilic oxygen source. This work constitutes the first general approach to enantioenriched cyclopropanone derivatives. Both the electronic and steric nature of the sulfonyl moiety, which serves as a base-labile protecting group and confers crystallinity to these cyclopropanone precursors, were found to have a crucial impact on the rate of equilibration to the corresponding cyclopropanone. The utility of these cyclopropanone surrogates is demonstrated in a mild and stereospecific formal [3+1] cycloaddition with simple hydroxylamines, leading to the efficient formation of chiral β-lactam derivatives.
- Jang, Yujin,Johnson, J. Drake,Jung, Myunggi,Lindsay, Vincent N. G.,Poteat, Christopher M.,Williams, Rachel G.
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supporting information
p. 18655 - 18661
(2020/08/21)
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- ELIMINATION AND ADDITION REACTIONS. PART 39. VARIATION OF NUCLEOFUGALITY WITH TRANSITION STATE STRUCTURE-1,3- AND 1,2-ELIMINATIONS FROM CARBANIONS COMPARED.
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Phenylsulphonyl-activated 1,3-eliminations have been investigated with the objective of determining nucleofugalities of six leaving groups.In cyclohexane-1,3-diyl and propane-1,3-diyl system unactivated 1,2-elimination of 'poor' leaving groups occurs faster than 1,3-elimination.In 2,2-dimethylpropane-1,3-diyl substrates, however, quantitative 1,3-eliminations occur and the nucleofugalities of Br, Cl, OTs, PhSO2, PhS, PhO, have been determined.In a linear free energy relationship extending over 15 pKa units and 12 rank units, an excellent correlation of nucleofugality with the pKa of the conjugate acid of the leaving group is found.It is concluded from the comparison with 1,2-eliminations previously studied that 1,3-elimination involves considerable leaving group separation and ring formation in the transition state.With bromide as leaving group, the 2,2-dimethylpropane-1,3-diyl system is 1000 times more reactive in cyclopropane formation than the propane-1,3-diyl system; this is the first quantitation of the Thorpe-Ingold effect in homocyclic ring formation.With chloride and tosylate leaving groups, smaller accelerations are observed.
- Issari, Bahram,Stirling, Charles J. M.
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p. 1043 - 1052
(2007/10/02)
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- Intramolecular Reactions. Part 12. Ring Size and Leaving Group Effects on Inter- and Intra-molecular Nucleophilic Substitution by Carbanions
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In cyclisations of aryl ο-halogenoalkyl ketones to aryl cycloalkyl ketones with base, cyclopropanes are formed up to 23000 times faster than cyclopentanes.Hydrogen-deuterium exchange experiments and very low bromide-chloride ratios (1.9) for three-membered ring formation are consistent with rate-determining deprotonation of the ketone.By contrast, in five-membered ring formation, hydrogen-deuterium exchange adjacent to the carbonyl group occurs much faster than cyclisation and the chloride-bromide ratio is 'normal' at 99.In formation of arylsulphonylcyclopropanes from arylsulphonylpropyl arenesulphonates, the Hammett ρ value for the leaving group is +1.7, and for intermolecular substitution by bis-sulphonyl stabilised carbanions, +1.2.Attempts to obtain ρLG values for five-membered ring formation were frustrated by competing intermolecular reactions.The results are discussed against the background of previous work on ring formation by intramolecular nucleophilic substitution.
- Bird, Roger,Griffiths, Gwerydd,Griffiths, Gwynfor F.,Stirling, Charles J. M.
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p. 579 - 584
(2007/10/02)
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