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Certain enolizable a-halo-and a-methoxy-substituted ketones undergo rapid reaction with lithium diisopropylamide (LDA) to give reduction products via formal hydride transfer to the carbonyl in competition with enolizal tion. The reducing agent has been verified as LDA by isolation of the oxidized form, the isopropylimine of acetone. This nitrogen analogue of the Meerwein-Ponndorf-Verley reduction gives stereochemistry analogous to that of borohydride or lithium aluminum hydride reductions. From a synthetic standpoint the reduction process can be circumvented in favor of enolization by use of lithium tetramethylpiperidide or lithium hexamethyldisilazide. Reaction of LDA with nonenolizable ketones also leads to reduction, but this process stops short of completion. This has been interpreted in terms of competing nucleophilic addition of LDA to the carbonyl to give an adduct which reverts to starting ketone upon addition of water. Addition of a "ketone scavenger" (methyllithium) to the reaction mixture prior to water quenching does not eliminate the starting ketone. These experiments support the intervention of a 1.2-ketone-LDA adduct.Lithium diisopropylamide is widely used in synthesis as a hindered, nonnucleophilic base, effecting rapid, kinetically controlled enolization of ketones usually in high yield.2 During attempts to prepare enolate anions from a variety of enolizable a-halo and a-methoxy ketones by treatment with lithium diisopropylamide (LDA) we have found that, surprisingly, many of these substrates undergo reduction of the carbonyl group in competition with expected enolization. These reactions, over within minutes in ether or tetrahydrofuran (THF) solvent a t -78 "C, produce mixtures of reduction and enolization products in which for some ketones the former greatly predominates. Herein we describe the extent of such reduction for several types of ketones with varied a-substituents, the stereochemistry of the reduction, and the interactions of LDA with some nonenolizable ketones as well. Results and Discussion Reaction of a-Halo and a-Methoxy Ketones with LDA.We are aware of no reported cases in whi,ch LDA has caused reduction of an enolizable k e t~n e ;~ thus we were extremely surprised on examination of the products from the -78 OC reaction of phenacyl bromide 1 with LDA, followed by acetic 0 OAc OAc I 1. LDA.THF, -78 "c I 2. AC,O, -78 O c -PhC=CHBr + PhCHCH,Br 1 2 3anhydride. Obtained in 80% yield was a nearly 2:l mixture of two products, the minor one of which consisted of the anticipated enol acetate 2 (a single isomer as indicated by the NMR spectrum, b u t with stereochemistry yet t o be determined4).The major product proved to be bromo acetate 3, as shown by spectral comparison with authentic material5 prepared via acetylation of the sodium borohydride reduction product of 1. Thus, in the reaction of phenacyl bromide with LDA, reduction of the carbonyl group occurs almost twice as rapidly as ketone enolization. This type of reaction is not unique t o phenacyl bromide.Reaction of LDA with endo-...

Successful conjugate additions to 2-bromocyclohexenone and 2-bromocyclopentenone have been achieved with a variety of lithium homocuprates, mixed cyanocuprates, and lithium tri-sec-butylborohydride as well. In all cases the resulting -bromo enolate anions could be trapped on oxygen with acetic anhydride; 3-substituted 2-bromo enol acetates were thus obtained regiospecifically and in good yields (Table II, 65-95%). Attempts to extend

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