Butyllithium, reaction with keto-esters

Ketones can also be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent (16-28). For an indirect way to convert carboxylic esters to ketones, see 16-82. A similar reaction with hindered aryl carboxylic acids has been reported. " Treatment of a p-amido acid with two equivalents of M-butyllithium, followed by reaction with an acid chloride leads to a p-keto amide.Carboxylic acids can be treated with 2-chloro-4,6-dimethoxy[l,3,5]-triazine and the RMgX/Cul to give ketones. " ... 

Subsequent treatment with sodium hydride in DMF gave the (Z)-alkene, a-isosafrole (577). If 573 reacted first with butyllithium and then with the analogous ester (578), the keto-phosphine oxide 579 was produced. Reduction of the ketone with sodium borohydride gave predominantly (>=6 1) the anti isomer 580, which gave the ( )-alkene 581 upon reaction with sodium hydride. An interesting application of this methodology is to extend the chain of an aldehyde by one carbon (R—CHO RCH2CHO). i ... 

When an ester has another carbonyl group at the P-position (such as in keto-ester 60), it is possible to form a dianion. Initial treatment of 60 with NaH leads to removal of the more acidic proton between the two carbonyl groups, and subsequent reaction with n-butyllithium gives the dianion 61.51 when 61 reacts with the iodide shown, alkylation occurs at the methyl group, the site of the least acidic proton in 60 and the more nucleophilic carhon in 61. The final product (62) was obtained as part of the Vedejs and Duncan synthesis of C( 16),C( 18)-bis-epi-cytochalasin D.51... 

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