844874-79-9Relevant articles and documents
The role of organic fluorine in directing alkylation reactions via lithium chelation
Tenza, Kenny,Northen, Julian S.,O'Hagan, David,Slawin, Alexandra M.Z.
, p. 1779 - 1790 (2004)
The fluorine of a fluoromethyl group displays a measurable chelation effect to lithium during α-methylation of an ester with lithium diisopropylamide (LDA) and methyl iodide. A series of esters is compared with F, H and O, 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. The diastereoselectivity of alkylation is explored comparing the coordination ability of H, F and OR substituents in the above model.
