Thorpe-Ingold effect

The Thorpe-Ingold effect or gem-dimethyl effect, or angle compression is an effect observed in organic chemistry where increasing the size of two substituents on a tetrahedral center leads to enhanced reactions between parts of the other two substituents. The effect was first reported by Beesley, Thorpe and Ingold in 1916 as part of a study of cyclization reactions ["CXIX.—The formation and stability of spiro-compounds. Part I. spiro-Compounds from cyclohexane" Richard Moore Beesley, Christopher Kelk Ingold and Jocelyn Field Thorpe, J. Chem. Soc., Trans., 1915, 107, 1080 DOI|10.1039/CT9150701080] .

A common application of this effect is addition of a quaternary carbon (e.g., a gem-dimethyl group) in an alkyl chain to increase the reaction rate and/or equilibrium constant of cyclization reactions. An example is this is an olefin metathesis reaction: [cite journal |journal=J. Org. Chem. |volume=61 |issue=25 |pages=8746–8749 |doi=10.1021/jo961600c|title=A Concise Total Synthesis of Dactylol via Ring Closing Metathesis |last=Fürstner |first=A |coauthors=Langemann, K.|year=1996]

:

One proposed explanation for this effect is that the increased size of the substituents increases the angle between them. As a result, the angle between the other two substituents decreases. By moving them closer together, reactions between them are accelerated. It is thus a kinetic effect.

:

The effect also has some thermodynamic contribution, the in silico strain energy decreases on going from cyclobutane to 1-methylcyclobutane and 1,1-dimethylcyclobutane by a value between 8 kcal/mole ["Conventional Strain Energy in Dimethyl-Substituted Cyclobutane and the gem-Dimethyl Effect" Ashley L. Ringer† and David H. Magers J. Org. Chem. 2007, 72, 2533-2537 DOI|10.1021/jo0624647] and 1.5 kcal/mole ["The gem-Dimethyl Effect Revisited" Steven M. Bachrach J. Org. Chem. 2008, 73, 2466-2468 DOI|10.1021/jo702665r] .

References