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 β‐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 alkyltransition metal complexes (a key step for the selectivity of important industrial processes such as alkene hydroformylation).

Halo Substituent Effects on Intramolecular Cycloadditions Involving Furanyl Amides

“…This is more electropositive than the alkene carbon of furan, and the electronegative halogen forms a stronger bond to the more electropositive carbon. Electropositive groups stabilize both carbocations and carbon centers carrying electronegative substituents by means of hyperconjugative and σ-inductive effects …”

Amino−Zinc−Enolate Carbometalation Reactions: Application to Ring Closure of Terminally Substituted Olefin for the Asymmetric Synthesis of cis- and trans-3-Prolinoleucine

“…Pathway A. It is well-known that the common organometallic (Li, Mg) reagents decrease in stability in the order Me > primary alkyl > secondary alkyl > tertiary alkyl and that the isomerization of linear to cyclic organometallic species implies a thermodynamically favored process . Thus, the synthesis of prolinoleucine via amino−zinc−enolate cyclization of α,β,β-trisubstituted olefins seems not to be thermodynamically favored.…”

Electronic Effects on the Stability of Isomeric Alkyl Transition Metal Compounds

“…This dependence is general for all alkyl−element compounds and, for main group compounds, is in fact a fairly well-known general principle of physical organic chemistry: electronegative groups bind preferentially to tertiary and secondary alkyl groups; electropositive groups prefer methyl and primary alkyl groups. This correlation was first pointed out as early as 1968 and has been much discussed since. − Its origin has been variously ascribed to electronegativity effects, 5c,g, to electrostatic interactions between partial charges, 5a,h,i to repulsion between C−H bonds,6c and more recently to orbital phase effects 5k…”