Gilman reagent

The Grignard and organolithium reagents are powerful but blunt: their carbon is so reactive it attacks almost any carbonyl head-on. Sometimes you want a gentler, more selective version of a carbon nucleophile, and the Gilman reagent is exactly that, the softer, more discriminating cousin in the organometallic family.

A Gilman reagent is a lithium dialkylcuprate, R2CuLi, made by combining two equivalents of an organolithium with a copper(I) salt. The carbon-copper bond is softer and less polar than the carbon-magnesium or carbon-lithium bond, so the carbon is a milder, 'softer' nucleophile. This softness gives Gilman reagents two signature uses. First, conjugate (1,4) addition: with an alpha,beta-unsaturated carbonyl (an enone, C=C-C=O), a Gilman reagent adds its alkyl group to the distant carbon of the C=C double bond rather than directly to the carbonyl carbon, the opposite preference to a Grignard, which tends to add right at the carbonyl (1,2). Second, cross-coupling: Gilman reagents will replace the halide of an alkyl, vinyl, or aryl halide with their R group, stitching two carbon fragments together to make a new C-C bond.

Gilman reagents fill an important niche: they are the go-to choice when you specifically want conjugate addition (delivering an alkyl group to the beta carbon of an enone) or a coupling that organolithiums and Grignards do poorly. The trade-off for their mildness is that they are less reactive overall, so for a simple aldehyde or ketone you would just reach for a Grignard instead. Choosing between hard (Grignard, RLi) and soft (Gilman) nucleophiles to control 1,2 versus 1,4 addition is a classic strategic decision.