Role of Aggregates in Claisen Acylation Reactions of Imidazole, Pyrazole, and Thioesters with Lithium Enolates in THF<sup>1</sup>

Streitwieser, Andrew; Leung, Simon Shun-Wang; Kim, Yeong-Joon

doi:10.1021/ol990604b

Cited by 30 publications

(6 citation statements)

References 7 publications

(9 reference statements)

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“…Lithium enolates have long been known to be frequently aggregated in ethereal solvents. − We have recently reported the aggregation equilibrium constants in THF of several lithium and cesium enolates. − In the present paper these studies are extended to the lithium (LiPhPAT, 1-Li ) and cesium (CsPhPAT, 1-Cs ) enolates of 2,6-diphenyl-α-tetralone. The ketone, PhPAT, 1 , is related to the p -phenylisobutyrophenone studied previously, , but the enolates are more conjugated.…”

Section: Introductionmentioning

confidence: 94%

Aggregation and Alkylation of Enolates of 2-Phenyl-α-tetralone and 2,6-Diphenyl-α-tetralone¹

2000

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The cesium (1-Cs, CsPhPAT) and lithium (1-Li, LiPhPAT) enolates of 2,6-diphenyl-R-tetralone, 1, and the lithium enolate (2-Li, LiPhAT) of 2-phenyl-R-tetralone, 2, are present in dilute THF solution as monomers and dimers with K 1,2 ) 1810 (1-Cs, CsPhPAT), 2650 (1-Li, LiPhPAT), and 1930 (2-Li, LiPhAT) M -1 . These values were obtained by singular value decomposition analysis of the UV spectra and by the dependence of ion pair pK's with concentration. On the ion pair pK scales previously defined, the monomers have pK ) 17.80 (1-Cs, CsPhPAT) and 11.14 (1-Li, LiPhPAT). The monomers are much faster than dimers in alkylation reactions; reaction products from alkyl halides are those of C-alkylation, but 1-Cs (CsPhPAT) with methyl sulfonates gives large amounts of O-alkylation. Comparison with previous results shows that the reactivity of cesium enolates parallels their basicity but that lithium enolates show no correlation between ion pair pK and alkylation reactivity.

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Section: Introductionmentioning

confidence: 94%

Aggregation and Alkylation of Enolates of 2-Phenyl-α-tetralone and 2,6-Diphenyl-α-tetralone¹

2000

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“…This small difference is in sharp contrast to our previous aggregate comparisons for n -BuLi dimer and tetramer, which gave much larger numbers. The Streitwieser group has also measured several aggregate relative reactivities and also found relatively small values …”

Section: Rinmr Studies Of Enolate Formation and Reactivitymentioning

confidence: 99%

What’s Going on with These Lithium Reagents?

Reich

2012

J. Org. Chem.

118

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This Perspective describes a series of research projects that led the author from an interest in lithium reagents as synthetically valuable building blocks to studies aimed at understanding the science behind the empirical art developed by synthetic chemists trying to impose their will on these reactive species. Understanding lithium reagent behavior is not an easy task; since many are mixtures of aggregates, various solvates are present, and frequently new mixed aggregates are formed during their reactions with electrophiles. All of these species are typically in fast exchange at temperatures above -78 °C. Described are multinuclear NMR experiments at very low temperatures aimed at defining solution structures and dynamics and some kinetic studies, both using classic techniques as well as the rapid inject NMR (RINMR) technique, which can in favorable cases operate on multispecies solutions without the masking effect of the Curtin-Hammett principle.

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“…Lithium enolates represent a class of powerful reagents for synthesis. Much is known about their solution structures and aggregation states, ,,,,,, but our understanding of the individual reactivity and rates of interconversion of the various homo and mixed aggregates known to be involved in their chemistry (of interest from Curtin–Hammett considerations) is in a more primitive state. , We address here the dynamics and chemistry of several aggregates and mixed aggregates of the lithium enolate of 4-fluoroacetophenone ( 1-Li ).…”

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Mechanistic Studies of the Lithium Enolate of 4-Fluoroacetophenone: Rapid-Injection NMR Study of Enolate Formation, Dynamics, and Aldol Reactivity

2011

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Lithium enolates are widely used nucleophiles with a complicated and only partially understood solution chemistry. Deprotonation of 4-fluoroacetophenone in THF with lithium diisopropylamide occurs through direct reaction of the amide dimer to yield a mixed enolate-amide dimer (3), then an enolate homodimer (1-Li)(2), and finally an enolate tetramer (1-Li)(4), the equilibrium structure. Aldol reactions of both the metastable dimer and the stable tetramer of the enolate were investigated. Each reacted directly with the aldehyde to give a mixed enolate-aldolate aggregate, with the dimer only about 20 times as reactive as the tetramer at -120 °C.

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Role of Aggregates in Claisen Acylation Reactions of Imidazole, Pyrazole, and Thioesters with Lithium Enolates in THF¹

Cited by 30 publications

References 7 publications

Aggregation and Alkylation of Enolates of 2-Phenyl-α-tetralone and 2,6-Diphenyl-α-tetralone¹

Aggregation and Alkylation of Enolates of 2-Phenyl-α-tetralone and 2,6-Diphenyl-α-tetralone¹

What’s Going on with These Lithium Reagents?

Mechanistic Studies of the Lithium Enolate of 4-Fluoroacetophenone: Rapid-Injection NMR Study of Enolate Formation, Dynamics, and Aldol Reactivity

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Role of Aggregates in Claisen Acylation Reactions of Imidazole, Pyrazole, and Thioesters with Lithium Enolates in THF1

Cited by 30 publications

References 7 publications

Aggregation and Alkylation of Enolates of 2-Phenyl-α-tetralone and 2,6-Diphenyl-α-tetralone1

Aggregation and Alkylation of Enolates of 2-Phenyl-α-tetralone and 2,6-Diphenyl-α-tetralone1

What’s Going on with These Lithium Reagents?

Mechanistic Studies of the Lithium Enolate of 4-Fluoroacetophenone: Rapid-Injection NMR Study of Enolate Formation, Dynamics, and Aldol Reactivity

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Resources

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Role of Aggregates in Claisen Acylation Reactions of Imidazole, Pyrazole, and Thioesters with Lithium Enolates in THF¹

Aggregation and Alkylation of Enolates of 2-Phenyl-α-tetralone and 2,6-Diphenyl-α-tetralone¹

Aggregation and Alkylation of Enolates of 2-Phenyl-α-tetralone and 2,6-Diphenyl-α-tetralone¹