A-proton abstraction

Protonated molecule. An ion formed by interaction of a molecule with a proton abstracted from an ion, as often occurs in chemical ionization according to the reaction ... 

The reaction with methanesulfonyl chloride in the presence of a proton abstracter like triethyl amine gave not the enamine, but a cyclic amino-sulfone (64). 

FIGURE 19.6 The phosphoglncoisomerase mechanism involves opening of the pyranose ring (Step A), proton abstraction leading to enediol formation (Step B), and proton addition to the double bond, followed by ring closure (Step C). 

Strong bases are required to abstract an a-proton from iron-acyl complexes (see also Houben-Weyl, Volume 13/9a, p 417). Such deprotonations are usually conducted in moderately polar solvents such as tetrahydrofuran. The archetypal complexes 1 and 2 illustrate most of the factors influencing a-proton abstraction. 

Treatment of the /J-hydroxy complex 15 with two equivalents of strong base followed by alkylation produces a mixture of the diastereomers 20 and 21 with an anomalously low d.r.27. The low degree of diastereofacial discrimination has been rationalized by invoking the formation of both rotamers of the initially formed alkoxide, 16 and 17. Rotamer 16 undergoes a-proton abstraction by a second equivalent of base to form the chelated dianionic Tf-enolate 18 which upon alkylation affords the usual diastereomer 20. Rotamer 17 is thought to rapidly transform to a metallo-lactone species by intramolecular attack of the alkoxide upon the proximate carbon monoxide ligand, which must occur faster than conversion to the less sterically encumbered conformer 16. Subsequent deprotonation to generate dianion 19, which is constrained to exist as the unusual Z-enolate, followed by alkylation provides the other diastereomer 21, which is formed in an amount nearly equal to 20. 

The cyclic cobalt-acyl complex 1 undergoes a-proton abstraction from the least-hindered face opposite the phosphane ligand upon treatment with lithium hexamethyldisilazide at 0 °C to generate the chiral enolate species 283. Treatment of 2 with primary iodoalkanes diastereoselec-tively produces the alkylated cobaltocycles 3 also via attack of the reagent on the face opposite the bulky phosphane. 

The two-electron process is either a hydride transfer or a proton abstraction followed by two-electron transfer. 

All presently known phosphamethin-cyanines were prepared according to our original procedure (1964) in which two quaternary salts of a heterocyclic base (e. g. 4) are condensed with tris-hydroxymethyl-phosphine 5 in the presence of a proton-abstracting base The preparation ofbis-[N-ethyl-benzothiazole(2)]-phosphamethin-cyanine-tetrafluoroborate 6 illustrates the synthetic sequence. A mixture of 2 moles of N-ethyl-2-chlorobenzothiazolium-tetrafluoroborate 4 and 1 mole of tris-hydroxymethyl-phosphine 5 in dimethylformamide is slowly reacted with ethyl-di-isopropylamine or pyridine at 0 °C. Addition of water immediately affords the crystalline cyanine dye 6 in ca. 45% yield ... 

The second class of TAM RE AC s inventory includes the reactions between the coordinated ligands and external organic reagents. We divide these reactions into nucleophilic and electrophilic attacks and consider them as acid-base interactions. Table III presents their general description. The nucleophilic attacks are either addition reactions to unsaturated coordinated ligands (Reactions 44-46) or abstraction reactions (usually a proton abstraction, Reactions 47-50). The electrophilic attacks are similarly addition reactions (Reactions 51 and 52) and abstraction reactions (usually a hydride abstraction, Reactions 53-59). Reactions 60 to 63 represent some other intermolecular reactions. 

The mutation at Lys-258 was carried out to replace Lys with Ala.16,39 This mutant lost activity by more than 106-fold compared to the wild-type enzyme. Other amino acids, such as Met and Arg, were also introduced into this position.16 It was found that enzymic activity in these mutants diminished significantly. In contrast, spectroscopic studies showed that Lys-258 mutants incubated with Asp or /J-hydroxy-Asp exhibited spectral changes almost identical with those of the wild-type enzyme incubated with a pseudosubstrate, a-Me-Asp. a-Me-Asp is known to give a Michaelis complex in which the catalytic process is seized prior to the a-proton abstraction step because of the absence of the a-proton in a-Me-Asp. This suggested that in the mutants the reaction was stopped at the step just prior to the a-proton removal. Both activity and spectrum studies supported the catalytic role of Lys-258. 

The alanine racemization catalyzed by alanine racemase is considered to be initiated by the transaldimination (Fig. 8.5).26) In this step, PLP bound to the active-site lysine residue forms the external Schiff base with a substrate alanine (Fig. 8.5, 1). The following a-proton abstraction produces the resonance-stabilized carbanion intermediates (Fig. 8.5, 2). If the reprotonation occurs on the opposite face of the substrate-PLP complex on which the proton-abstraction proceeds, the antipodal aldimine is formed (Fig. 8.5,3). The subsequent hydrolysis of the aldimine complex gives the isomerized alanine and PLP-form racemase. The random return of hydrogen to the carbanion intermediate is the distinguishing feature that differentiates racemization from reactions catalyzed by other pyridoxal enzymes such as transaminases. Transaminases catalyze the transfer of amino group between amino acid and keto acid, and the reaction is initiated by the transaldimination, followed by the a-proton abstraction from the substrate-PLP aldimine to form a resonance-stabilized carbanion. This step is common to racemases and transaminases. However, in the transamination the abstracted proton is then tranferred to C4 carbon of PLP in a highly stereospecific manner The re-protonation occurs on the same face of the PLP-substrate aldimine on which the a-proton is abstracted. With only a few exceptions,27,28) each step of pyridoxal enzymes-catalyzed reaction proceeds on only one side of the planar PLP-substrate complex. However, in the amino acid racemase... 

These results indicate that the naphthalene radical anion is not stable to the solvent tetrahydrofuran at room temperature on a time scale of 100 hours. Decomposition pathways are alkali metal dependent. Sodium and potassium naphthalene attack THF through a proton abstraction, cycloreversion mechanism, as previously described by Bates for the butyllithium/THF system (27). Lithium naphthalenide attacks the THF not only by the Bates mechanism but also by a nucleophilic ring opening, as is implicit in earlier high temperature work on lithium naphthalenide in THF (28) and in work on the attack of THF by tritylmagnesium bromide (29). The two smaller alkali metals, lithium and sodium, leave behind a... 

Fig 3 Bransted plot for water-promoted a-proton abstraction for a series of protonated acetophenones [411 (Dubois et ai, 1981)... 

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