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

Grignard Reactions — The Master Nucleophile

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Grignard reagent (RMgX) acts as R:- (carbanion equivalent). It adds to C=O:

Carbonyl SubstrateProduct (after H3O+)
HCHORCH2OH (primary alcohol)
R'CHORR'CHOH (secondary alcohol)
R'COR"RR'R"COH (tertiary alcohol)
CO2 (dry ice)RCOOH (carboxylic acid, after hydrolysis)
Ethylene oxideRCH2CH2OH (primary alcohol, +2C)
R'COOR"RR'(R)COH (tertiary, 2 eq RMgX added)
R'CNR'COR (ketone, after hydrolysis of imine intermediate)

Critical limitations: RMgX is destroyed by any acidic H source — H2O, ROH, NH3, RNH2, RCOOH, terminal alkynes. Keep all reagents anhydrous.

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