Part of JOC-03 — Aldehydes, Ketones & Carboxylic Acids

Grignard Reagent — The Universal Carbon Nucleophile

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The Grignard reagent (RMgX, prepared from RX + Mg in dry ether) acts as R:- (carbanion equivalent). Product mapping: HCHO → RCH2OH (1° alcohol), RCHO → secondary alcohol, R2CO → tertiary alcohol, CO2 → RCOOH, ethylene oxide → RCH2CH2OH (1° alcohol +2C), ester → tertiary alcohol (2 eq RMgX), nitrile → ketone (after hydrolysis). Critical requirement: ALL reagents must be anhydrous — RMgX reacts with any acidic proton (H2O, ROH, NH3, RCOOH, terminal alkynes, HX). Even trace moisture destroys the reagent. RMgX is both a strong nucleophile and strong base — with 2° and 3° halides or bulky ketones, elimination can compete with addition. Organolithium (RLi) is similar but more reactive and more nucleophilic. For selective 1,4-addition to alpha,beta-unsaturated carbonyls, use R2CuLi Gilmancuprate\frac{Gilman}{cuprate} instead — RMgX gives 1,2-addition.

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