The fluorine of a fluoromethyl group displays a measurable chelation effect to lithium during a-methylation of an ester with lithium diisopropylamide (LDA) and methyl iodide. A series of esters is compared with F, H and 0, and the resultant diastereoselectivity is consistent with the intermediate capacity of F to chelate lithium relative to H and O. In a second system which involved comparing a tertiary organic fluorine with hydrogen, no such effect is apparent, most probably due to adverse steric effects. The absolute and relative stereochemistry of the predominant diastereoisomers are confirmed by X-ray crystallography of suitable crystalline derivatives in each case. It is concluded that there is a potential role for organic-bound fluorine to become involved in lithium chelation in well-designed enolate alkylation systems. (C) 2004 Elsevier B.V. All rights reserved.