Acidities of carbon acids. IV. Kinetic vs. equilibrium acidities as measures of carbanion stabilities. Relative effects of phenylthio, diphenylphosphino, and phenyl groups

Bordwell, F. G.; Matthews, Walter S.; Vanier, Noel R.

doi:10.1021/ja00835a048

Cited by 53 publications

(25 citation statements)

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“…Given the perceived challenge to the application of diphenylmethane (p K a = 32.2) 39 in allylic substitutions, we initiated our studies with the more acidic 2-benzylpyridine ( 1a , p K a = 28.2) 38 under the reaction conditions in eq 1. The desired product 3aa was formed in 80% assay yield (Table 1, entry 1).…”

Section: Resultsmentioning

confidence: 99%

“…We increased the assay yield of 3ca to 70% by using the more reactive base, KN(SiMe 3 ) 2 (entry 5). Unfortunately, further decreasing the acidity of the pronucleophile was challenging: using diphenylmethane ( 4aa , p K a = 32.3) 39 gave desired product 5aa in only 10% assay yield (entry 6). We next set out to optimize the reaction conditions for Pd-catalyzed allylic substitution with pronucleophiles with p K a ’s >30, such as diphenylmethane.…”

Section: Resultsmentioning

confidence: 99%

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Raising the pK_a Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions: Application of Diarylmethane Pronucleophiles

et al. 2013

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The Tsuji-Trost allylic substitution reaction provides a useful and efficient approach to construct C-C bonds between sp3-hybridized carbons. The widely accepted paradigm for classifying the mode of attack of nucleophiles on palladium π-allyl intermediates in the Tsuji-Trost reaction is based on the pKa of the pronucleophile: (1) stabilized or “soft” carbon nucleophiles and heteroatom nucleophiles (e.g., pronucleophiles with pKa’s < 25), and (2) unstabilized or “hard” nucleophiles (those from pronucleophiles with pKa’s > 25). One of the keys to the continuing development of allylic substitution processes remains broadening the scope of “soft” nucleophiles. Herein we report a general method for the room temperature Pd-catalyzed allylic substitution with diarylmethane derivatives (pKa’s up to 32). The synthetic significance of the method is that it provides a rapid access to products containing allylated diarylmethyl motifs. The method is general for a wide range of nucleophiles derived from diarylmethanes and heterocyclic derivatives. A procedure for the Pd-catalyzed allylic substitutions to afford diallylation products with quaternary centers is also described. With triarylmethanes and, alkylated diarylmethanes the corresponding allylated products are isolated. We anticipate that the described method will be a valuable complement to the existing arsenal of nucleophiles in Pd-catalyzed allylic substitutions. Mechanistic studies show that the nucleophile derived from diphenylmethane undergoes external attack on π-allyl palladium species under our reaction conditions. This unexpected observation indicates that diarylmethane derivatives behave as “soft” or stabilized nucleophiles. The results of this study indicate that the cutoff between “soft” and “hard” nucleophiles should be raised from a pronucleophile pKa of 25 to at least 32.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Raising the pK_a Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions: Application of Diarylmethane Pronucleophiles

et al. 2013

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“…is −1.1 V) and kinetic reasons (reduction is accompanied by little reorganization energy),24 the radical is rapidly reduced to the corresponding carbanion Ph 2 CH − . Since the latter is very basic (the p${K{{{\rm DMF}\hfill \atop {\rm a}\hfill}}}$ of Ph 2 CH 2 can be estimated to be 32.6)25a,b and the original sulfide is the strongest acid in solution (the p${K{{{\rm DMF}\hfill \atop {\rm a}\hfill}}}$ of Ph 2 CHSPh is 27.2,25a,c and that of 1 a was estimated to be only slightly larger;15d similarly, the p${K{{{\rm DMF}\hfill \atop {\rm a}\hfill}}}$ values of the other sulfides should not be significantly smaller than 27), a self‐protonation reaction occurs. By this mechanism,15b, 26 part of the reducible molecule is transformed into its conjugate base and becomes electroinactive at the applied potentials.…”

Section: Resultsmentioning

confidence: 99%

Electron Transfer to Sulfides and Disulfides: Intrinsic Barriers and Relationship between Heterogeneous and Homogeneous Electron‐Transfer Kinetics

Meneses

Antonello

Arévalo

et al. 2007

Chemistry A European J

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The electron-acceptor properties of series of related sulfides and disulfides were investigated in N,N-dimethylformamide with homogeneous (redox catalysis) and/or heterogeneous (cyclic voltammetry and convolution analysis) electrochemical techniques. The electron-transfer rate constants were determined as a function of the reaction free energy and the corresponding intrinsic barriers were determined. The dependence of relevant thermodynamic and kinetic parameters on substituents was assessed. The kinetic data were also analyzed in relation to corresponding data pertaining to reduction of diaryl disulfides. All investigated reductions take place by stepwise dissociative electron transfer (DET) which causes cleavage of the C(alkyl)--S or S--S bond. A generalized picture of how the intrinsic electron-transfer barrier depends on molecular features, ring substituents, and the presence of spacers between the frangible bond and aromatic groups was established. The reduction mechanism was found to undergo a progressive (and now predictable) transition between common stepwise DET and DET proceeding through formation of loose radical anions. The intrinsic barriers were compared with available results for ET to several classes of dissociative- and nondissociative-type acceptors, and this led to verification that the heterogeneous and the homogeneous data correlate as predicted by the Hush theory.

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“…The equilibrium acidities of organic acids do not necessarily correlate with their kinetic acidities [39,[43][44][45][46]. Deprotonations of sparsely polarized X-H groups which are accompanied by a large change in hybridization and geometry proceed more slowly than deprotonations with little rehybridization ("principle of least nuclear motion" [45]).…”

Section: The Kinetics Of Deprotonationsmentioning

confidence: 99%

The Alkylation of Carbanions

Dörwald

2004

Side Reactions in Organic Synthesis

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The deprotonation of organic compounds by strong, non-nucleophilic bases followed by C-alkylation with a suitable electrophile has become one of the most predictable and straightforward methods for formation of C-C bonds. The popularity of this chemistry is also a consequence of the often-seen close resemblance of feasible structural modifications by a deprotonation/alkylation strategy to an unsophisticated retrosynthetic analysis of a given target compound. Other reactions, which involve, for instance, substantial rearrangement of the carbon framework (e.g. Cope rearrangement, fragmentations, ring contractions or enlargements) are usually more difficult to take into account during retrosynthetic analysis.LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2]. Because the reactivity of an organometallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles.In this chapter the alkylation of carbanions with simple carbon electrophiles will be discussed, with special emphasis on the structure-reactivity relationship of the carbanion and on side reactions. In this context the term "carbanion" refers to an intermediate prepared by in-situ deprotonation of an organic compound, followed by optional cation exchange (transmetalation), which tends to be alkylated at carbon by soft electrophiles such as MeI or PhCHO. This type of reactivity is characteristic of enolates with an ionic M-O bond or for organometallic compounds with a strongly polarized or ionic M-C bond, M typically being an alkali metal, Mg, Cu, or Zn. Carbanions can, alternatively, also be prepared by halogen-metal exchange [3-8], sulfoxide-or sulfone-metal exchange [9-13], or by transmetalation of stannanes. The most suitable reagents for performing such metalating exchange reactions are organometallic compounds with a metal-bound secondary or tertiary alkyl group, such as tBuLi, sBuLi, iPr 2 Zn [14, 15], or iPrMgHal [6]. These reagents are thermodynamically less stable than organometallic compounds with primary alkyl 5 146 Scheme 5.1. Approximate relative rates of proton transfer in water at thermoneutrality (DpK a = 0) [35, 39, 51]. 147 Scheme 5.2. The effect of fluorine on the acidity of organic compounds [24, 62-65]. 148 Scheme 5.3. Dependence of the reactivity of carbanions on their basicity [68, 72-74]. Regioselectivity of Deprotonations and AlkylationsThe organic chemist is occasionally confronted with the problem that a compound has several differrent X-H groups of similar pK a . If only one of these is to be alkylated, one option would be to perform a regioselective deprotonation. This can sometimes be achieved by exploiting small differences be...

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Acidities of carbon acids. IV. Kinetic vs. equilibrium acidities as measures of carbanion stabilities. Relative effects of phenylthio, diphenylphosphino, and phenyl groups

Cited by 53 publications

References 1 publication

Raising the pK_a Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions: Application of Diarylmethane Pronucleophiles

Raising the pK_a Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions: Application of Diarylmethane Pronucleophiles

Electron Transfer to Sulfides and Disulfides: Intrinsic Barriers and Relationship between Heterogeneous and Homogeneous Electron‐Transfer Kinetics

The Alkylation of Carbanions

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Acidities of carbon acids. IV. Kinetic vs. equilibrium acidities as measures of carbanion stabilities. Relative effects of phenylthio, diphenylphosphino, and phenyl groups

Cited by 53 publications

References 1 publication

Raising the pKa Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions: Application of Diarylmethane Pronucleophiles

Raising the pKa Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions: Application of Diarylmethane Pronucleophiles

Electron Transfer to Sulfides and Disulfides: Intrinsic Barriers and Relationship between Heterogeneous and Homogeneous Electron‐Transfer Kinetics

The Alkylation of Carbanions

Contact Info

Product

Resources

About

Raising the pK_a Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions: Application of Diarylmethane Pronucleophiles

Raising the pK_a Limit of “Soft” Nucleophiles in Palladium-Catalyzed Allylic Substitutions: Application of Diarylmethane Pronucleophiles