Electronegativity Effects in Organic Synthesis: Differences in stability of isomeric substituted alkanes

Abstract

Selectivity is such an intellectually, economically, and ecologically important matter in organic synthesis that it is highly desirable to know all the factors, both kinetic and thermodynamic, which influence it. We were surprised by the high selectivity obtained in an equilibration of isomeric beta-thioalkyl trifluoroacetates, because the thermodynamic difference implied by this and other, similar, rearrangements did not appear to have been explained. It now appears that this difference is due to the thermochemical effect whereby polar substituents bind more strongly to alkyl groups of complementary polarity; in other words electronegative atoms prefer more ''procationic'' tertiary and secondary alkyl groups, electropositive ones prefer the more ''proanionic'' primary alkyl and methyl groups. This small but significant (1 to 7 kcal . mol(-1)) effect is well documented by thermochemical data, and has been described several times; it can be predicted qualitatively by Pauling's formula relating bond energy, bond polarisation, and electronegativity. We first describe how the electronegativity effect explains our observations: they are due to the higher electronegativity of oxygen and chlorine relative to that of sulfur. We then go on to show that it is useful for the interpretation of many other literature reports, ranging from the acid-catalysed isomerization of alkyl halides, to the carbocyclization of organozinc reagents, and the isomerization of alkyl-transition metal complexes (a key step for the selectivity of important industrial processes such as alkene hydroformylation).