Electrophilic Addition to Alkenes: The Relation between Reactivity and Enthalpy of Hydrogenation: Regioselectivity is Determined by the Stability of the Two Conceivable Products

Abstract

Although electrophilic addition to alkenes has been well studied, some secrets still remain. Halogenations, hydrohalogenations, halohydrin formations, hydrations, epoxidations, other oxidations, carbene additions, and ozonolyses are investigated to elucidate the relation of alkene reactivities with their enthalpies of hydrogenation (ΔHhyd ). For addition of electrophiles to unconjugated hydrocarbon alkenes, ln(k) is a linear function of ΔHhyd , where k is the rate constant. Linear correlation coefficients are about 0.98 or greater. None of the many previously proposed correlations of ln(k) with the properties of alkenes or with linear free-energy relationships match the generality and accuracy of the simple linear relationship found herein. A notable exception is acid-catalyzed hydration in water or in solvents stabilizing relatively stable carbocation intermediates (e.g., tertiary, benzylic, or allylic). (13) C NMR chemical shifts of the two alkene carbons also predict regioselectivity. These effects have not been noted previously and are operative in general, including addition to heteroatom-substituted alkenes.

Hydrogenative Cyclopropanation and Hydrogenative Metathesis

“…[33] This rather perplexing correlation [34] suggests that attack of the electrophilic carbene by the more nucleophilic site of the alkene partner might be selectivity-determining,w hich happens to be the terminus if R 1 = R 2 = H, but the internal position if R 1 = R 2 = Me ("Markovnikovsr ule"). [35,36] Under this premise, 2a could evolve via a6 -endo-trig transition state H into the cyclopropane 3a by an outersphere process,whereas 2fis geometrically poised for metallacycle formation (I)and hence metathesis to furnish cycloalkene 11 a. [37] This tentative mechanistic interpretation is in accord with additional stoichiometric control experiments (Scheme 7), which indicate that the course of the reaction responds to the polarization of the alkene bond in ag ive substrate.S pecifically, 1a provides cyclopropane 3a,w hereas enyne 22 containing ad ifluoroolfinic site gave the metathesis product 11 a;since hydrogen and fluorine are isosteric, this divergent outcome implies that the product-determining step is (largely) governed by electronic rather than steric factors.…”

Hydrogenative Cyclopropanation and Hydrogenative Metathesis

“…As shown in the accompanying paper, 21 leads to a carbene of increased electrophilicity which one does not expect to bolster metathesis . This rather perplexing correlation suggests that attack of the electrophilic carbene by the more nucleophilic site of the alkene partner might be selectivity‐determining, which happens to be the terminus if R 1 =R 2 =H, but the internal position if R 1 =R 2 =Me (“Markovnikov's rule”) . Under this premise, 2 a could evolve via a 6‐ endo ‐ trig transition state H into the cyclopropane 3 a by an outersphere process, whereas 2 f is geometrically poised for metallacycle formation ( I ) and hence metathesis to furnish cycloalkene 11 a…”

The quadrapolar character of the Markovnikov reaction transition state

“…This imaginary frequency is used to calculate a simple tunneling correction to the rate constant using the Wigner formula. 8 [34] The significance of this correction for the calculation at hand is found in the discussion section.…”

“…[2][3][4][5][6][7] A recent study has shown a correlation between the rates of electrophilic addition and the hydrogenation energy of a large number of systems. [8] This correlation apparently breaks down for H 2 O and for highly polar media or under acid-catalysis. Anti-Markovnikov addition can be achieved by appropriate catalysts.…”