Temperature-Dependent Alkylation of γ-Phenyl β,γ-Unsaturated Acid and Ester Systems in Hexamethylphosphortriamide-Tetrahydrofuran Solutions Using Lithium Diisopropylamide

Article abstract of DOI:10.1021/jo00203a011

The reactivities of some β,γ-unsaturated carboxylic acids and their methyl esters toward alkylation with methyl iodide using the lithium diisopropylamide-hexamethylphosphortriamide (LDA-HMPT) systems in THF have been investigated.The methylation selectivity of pent-3-enoic acid (2) and (1,2-dihydro-3-naphtyl)acetic acid (6) on using 1.0 equiv. of methyl iodide is high, the α-mono- to α,α-dimethylation ratios at -78 deg C being >20.The selectivity is substantially lower for styrylacetic acid (4) and increases with increasing temperature from 2.3 at -78 deg C to 8.5 at -10 deg C.The occurrence of dimethylation is ascribed to intermolecular proton exchange between the monomethylated species IIa and the nonmethylated species Ia.For the β,γ-unsaturated esters the methylation selectivity is somewhat higher than that for the corresponding carboxylic acids.