Thorpe–Ingold effect

The Thorpe–Ingold effect, gem-dimethyl effect, or angle compression is an effect observed in chemistry where large substituents favor ring closure and intramolecular reactions. The effect was first reported by Beesley, Thorpe, and Ingold in 1915 as part of a study of cyclization reactions. It has since been generalized to many areas of chemistry. The Thorpe–Ingold effect, gem-dimethyl effect, or angle compression is an effect observed in chemistry where large substituents favor ring closure and intramolecular reactions. The effect was first reported by Beesley, Thorpe, and Ingold in 1915 as part of a study of cyclization reactions. It has since been generalized to many areas of chemistry. The comparative rates of lactone formation (lactonization) of various 2-hydroxybenzenepropionic acids illustrate the effect. The placement of an increasing number of methyl groups accelerates the cyclization process. One 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 of this is an olefin metathesis reaction: