Dipole-Stabilized Carbanions from Esters: α-Oxo Lithiations of 2,6-Substituted Benzoates of Primary Alcohols

Article abstract of DOI:10.1021/jo00324a030

The synthetic utility of dipole-stabilized carbanions from esters is illustrated by the preparations, α-oxo lithiations, electrophilic substitutions, and cleavages of the 2,4,6-triisopropylbenzoates and the 2,6-bis(dimethylamino)-3,5-diisopropylbenzoates of primary alcohols, 2 and 3, respectively.Typical electrophiles used in this methodology include primary alkyl halides, aldehydes, ketones, trimethylsilyl chloride, and tri-n-butyltin chloride.Cleavages of the substituted esters of 2 are accomplished with lithium aluminum hydride while hydrolyses of derivatives of3 can be achieved under acidic conditions.The 2,6-substitutions of 2 and 3 are considered to enforce orthogonality of the carbonyl group and the phenyl ring and thereby to inhibit addition to the carbonyl by the organolithium base used for the metalation by placing the substituents in the trajectory for nucleophilic addition along the LUMO of the carbonyl.The acidic hydrolysis of 3 under conditions where 2 is stable is attributed to protonation of the dimethylamino group which provides subsequent assistance for nucleophilic addition.These metalations provide the key steps in the preparation of secondary α-lithio alcohol synthetic equivalents from primary alcohols.Lithiation of 1'-methylbenzyl 2,4,6-triisopropylbenzoate proceeds α to oxygen as expected, but attempts to prepare analogous unactivated tertiary α-lithio esters were unsuccessful.The lithiation of 2'-methoxyethyl 2,4,6-triisopropylbenzoate is followed by elimination of methoxide and α-oxo metalation of the resulting vinyl ester.Lithiation of allyl 2,4,6-triisopropylbenzoate provides 1-(2,4,6-triisopropylphenyl)-1,2-butanedione by rearrangement.