Deprotonation pathway

In another interesting turn of event, while we were attempting to add acetate anion in a 1,4-fashion into the enone system of 45, we isolated ene-dione 49b when using KOAc in the presence of 18-crown-6 (Scheme 8.11). While this was not what we had anticipated, it turned out to be a known protocol developed by Komblum and DeLaMare to ring-open endoperoxides through a deprotonation pathway [55]. It is noteworthy that ene-dione 49b did not equilibrate to the ene-trione 49b which could suffer from the aforementioned HDA pathway as we had also suffered from [47c],... 

If only the acid/base proton dissociation of complex MOH is considered, Scheme 4 is simplified to include only steps (a) and (b) therein. According to this model, (I) is the primary deprotonation pathway in acidic medium, while (III) is of importance in basic media. On the other hand, direct proton transfer (II) can occur around neutral pH values. 

As shown by these equations, the different deprotonation pathways differ in their transition-state structures a 2/1 base-oxirane trimer of type 30 for a-deprotonation, compared with a 1/1 base-oxirane dimer of type 31 for yS-deprotonation (Scheme 13). Similar results have been reported for the -deprotonation of cyclohexene oxide by proline-derivated amides. ... 

In light of these kinetic studies, a decrease in the concentration of the ligand is predicted to favor the a-deprotonation pathway. On the contrary, further studies show that the a/yS deprotonation ratio is independent of this concentration. This observation, associated with deuterium-labeling studies, suggests the involvement of the a-deprotonation in the formation of the ally lie alcohols at low concentration of ligand. Conversely, the presence of highly coordinating solvents such as HMPA, which break up ion pairs, suppresses both a-deprotonation and nucleophilic addition (Scheme 14) . ... 

The deprotonation pathway in the CL reaction of Ln is proposed as follows Ln (Neutral) —> M440 ( Anion-2 , Anion-0+K+ or Anion-2+2K+ ) —> M420 ( Anion-3+DMSO+K+ ). The DMSO molecule between K+ and Anion-3 makes absorption peaks shift to shorter wavelengths. Furthermore, we are going to study the ionized states of M440 and M420 by experimental techniques of IR and H-NMR. 

Figure 14. Dependence on AG°n.cage of the deprotonation pathway (see Chart IX) of the aminium cation derived from triethylamine. The ratio 2IJIf of polarizations of the olefinic a and j8 protons of diethylvinylamine (cf. Fig. 13) is shown as function of AG°, cage a value of about — 1 indicates complete in-cage deprotonation, a value of about +9 exclusive deprotonation outside the cage. (Top) Variation of AG ., . by variation of the sensitizer. (Bottom) By variation of the solvent. The solid lines are a global best fit to both data sets. The labels (see [94e]) at the curves denote sensitizer and solvent, respectively. [Reproduced from ref. [94e] with permission. Copyright 1994 VCH Verlagsgesellschaft Weinheim.]...

A second, closely related experiment was conducted with the Barton ester 6 [4]. Here, the results were cleaner owing to the stronger C-H bonds, which effectively eliminated the deprotonation pathway and the formation of any allyl radicals. Moreover, as expected, because of the electron-donating effect of the para-methoxy group the diffusively free radical cation 8 could now be observed even in pure acetonitrile (Scheme 2). However, the telling feature of this series of experiments was... 

Asymmetric induction in these reactions occurs either in the first deprotonation step [Eq. (la)] or in a postdeprotonation step [1] [(Eq. (lb)]. When the enantioselection occms in the deprotonation step, a proton is stereoselectively removed by a chiral base from a prochiral substrate to provide a configuration-ally stable enantioemiched carbanion, which reacts with an electrophile giving an enantioenriched product. This enantiodetermining pathway is termed asymmetric deprotonation . In fact, reactions of a-oxy and a-amino carban-ions are often controlled through an asynunetric deprotonation pathway (Fig. 2) [1,2]. 

Enantioselectivity through an asynunetric deprotonation pathway is largely dependent on the configurational stability of the carbanion and the interaction between a substrate and a chiral base. On the other hand, when the enantioenriched product is formed in the reaction with an electrophile, even though the deprotonation gives the racemic carbanion, this pathway is termed asymmetric substitution [1], Enantioselection through an asymmetric substitution path-... 

Silylation of a-sulfonyl carbanions may proceed through an asymmetric deprotonation pathway [Eqs. (13) and (14)] [57]. Thus, Simpkins has shown that silylated products are obtained with certain enantioselectivities when TMSCl is present in the reaction mixture during the deprotonation reaction with a cam-... 

In a foUow-up paper, the group disclosed a possible mechanism for direct arylation based on a concerted metalation—deprotonation pathway (Scheme 11) (2010JOC8180). Kinetic experiments revealed a zero order... 

DFT calculations have been reported of the copper-catalysed reaction of A-methyl indoles with amides, which result in amidation at the 2-position. The results show that a concerted metalation—deprotonation pathway does not explain the observed regioselectivity. Instead, a four-centre reductive elimination involving the transition state (80) is proposed. The reaction is likely to be completed by proton transfer from the amidated carbon atom to the butoxy ligand. Copper-catalysed reaction of azoles or polyfluoroarenes with sulfoximines may produce A-aryl sulfoximines. Owing to the mild reaction conditions, enantiopurity in the starting sulfoximine is retained in products such as (81). 

Later, Dixneuf, Jutand, and co-workers reported kinetic data on the reaction of [Ru(OAc)2(p-cymene)] with 2-phenyipyridine in acetonitrile that revealed a different C-H bond activation mechanism. " This involves an intermolecular deprotonation pathway via Se3 mechanism which is an autocatalytic process catalysed by the acetic acid produced during the C-H activation (Scheme 2). Kinetic analysis of the reaction between 6 and 2-phenylpyridine to give 9 showed that this process was considerably accelerated by the presence of acetic acid and water. A drastie retarding effect in the presence of 3 equivalents of K2CO3 was also observed which is consistent with the autocatalytic process, as K2CO3 neutralises the required AcOH. In order to explain the importance of the base, " it is essential to take into account the lasts steps to close the catalytic cycle. In most cases the C-H activation is followed by oxidative addition and reductive elimination to recover the active catalytic species. The C-H activation of 2-phenylpyridine was much faster (27 °C) than the following oxidative addition (120 °C) that becomes rate-determining. 

A more appealing strategy for arene C—H functionalizations involves the use of simple benzene derivatives lacking DGs. The overall pathway for such transformations entails metal mediated C—H activation to afford the metal-aiyl intermediate Ai M followed by subsequent functionalization of Ai M to release the desired product (Scheme 24.1). The C—H activation step can proceed via oxidative addition, sigma bond metathesis, or concerted metalation deprotonation pathway. The exact mechanism of C—H cleavage is dependent on the nature of the metal and the ancUlaiy ligands [1,3]. 

The ruthenium-catalysed arylation, by aryl halides, of benzylic amines carrying a pyridine coordinating group is thought to involve a concerted metallation-deprotonation pathway to give intermediates such as (96), followed by oxidative addition of the aryl halide to ruthenium and then reductive elimination. The reaction can be successM with aryl chlorides, as well as bromides and iodides, but here there are mechanistic differences. The ability of ruthenium to activate remote ring positions to electrophilic substitution has been referred to earlier, see Ref. 97. The reaction of ruthenium-coordinated 2-pyridyl arenes (51) with secondary alkyl halides has been shown to result in the formation of metfl-alkylated products. ... 

Peterson Oleflnation Reactions. McNulty and Das have shown that the treatment of chlorobis(trimethylsilyl)methane (1) with 5-BuLi at low temperatures favors lithium-halogen exchange processes over deprotonation pathways (eq 1)The resulting lithi-ated derivative 2 undergoes Peterson oleflnation reactions with a... 

The Gibbs energy barriers for the lowest-energy deprotonation pathways with the different R... 

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