Why Is Alkylation of an Enolate Accompanied by So Much Polyalkylation?

Abstract

[reaction: see text] The lithium enolate 1-Li of 6-phenyl-alpha-tetralone forms a monomer-tetramer equilibrium in THF at 25 degrees C with K(1,4) = 4.7E+10 M(-3). The lithium enolate 2-Li, however, forms a monomer-dimer equilibrium with K(1,2) = 3800 M(-1). In both cases reaction with benzyl bromide is dominantly with the monomer. The results support an earlier conjecture of House that alkylation of an enolate is frequently accompanied by extensive polyalkylation because the less substituted enolates are more aggregated.

Aggregation and Reactivity of the Cesium Enolate of 6-Phenyl-α-tetralone: Comparison with the Lithium Enolate1

“…The object is a better quantitative understanding of the effect of the steric environment of the enolate on its aggregation and reactivity. The present study supplements our previous report on the aggregation and reactivity of the corresponding lithium enolate, LiPAT …”

“…The p K of CsPAT, 23.39, is substantially higher than that of the corresponding lithium enolate, LiPAT, 14.22 …”

“…We had shown previously that the alkylation reactions of several lithium and cesium enolates occur dominantly with the enolate monomers. ,− In the present work, we include additional examples of such alkylations because these are ion-pair S N 2 reactions and it would be valuable to have examples of structural effects for comparison with ionic S N 2 reactions in more polar solvents. Earlier studies of relative reactivities of different enolates in ether are less useful for this purpose because the role of aggregation was not determined. − Lithium halides have been shown to form mixed aggregates with lithium enolates; , although such mixed aggregates have not been demonstrated for cesium salts, we followed our usual procedure of measuring initial rates.…”

“…In recent papers, we have described the aggregation and reactivity of the lithium and cesium enolates of several ketones: p -phenylisobutyrophenone, LiPhIBP and CsPhIBP, 2-phenylcyclohexanone, LiPCH and CsPCH, 2-( p -biphenylyl)cyclohexanone, LiBPCH and CsBPCH, 2,6-diphenyl-α-tetralone, LiPhPAT and CsPhPAT, and the lithium enolates of p -phenylsulfonylisobutyrophenone, LiSIBP, 6-phenyl-α-tetralone, LiPAT, and 2-benzyl-6-phenyl-α-tetralone, LiBnPAT . In the present paper, we extend the study to the cesium enolate, CsPAT, of 6-phenyl-α-tetralone, PAT.…”

The synthesis of bioactive indolocarbazoles related to K-252a

“…Over-alkylation is a well known problem in ketone enolate chemistry, particularly for cyclopentanones, and under these conditions it seems that enolate equilibration leading to disubstituted products is highly favoured. 31 Although we were unable to control mono-alkylation, it did prove possible to force alkylation to give good yields of a dialkylated product, for example the dibenzylketone 45, obtained in 71% yield, using two equivalents of base.…”