Acidic substrates deprotonation

Racemization of the Amino Acid Substrate Deprotonation of the a-carbon of the amino acid leads to tautomerization of the Schiff base to the quinonoid ketimine, as shown in Figure 9.2. The simplest reaction that the ketimine can undergo is reprotonation at the now symmetrical a-carbon. This is not a stereospecific process therefore, displacement of the substrate by the reactive lysine residue results in the racemic mixture of d- and L-amino acid. 

The slow protonation rate of the conjugated anion of the sulphone (1st step) leads to the obtainment of a pseudo one-electron process. However, no self-protonatiori process exists in the presence of an excess of a proton donor of lower pKa than that of the electroactive substrate and Figure 6a, curve 2 shows evidence for a two-electron step. Full substitution on the a carbon, as in the case of phenyl 2-phenylbut-2-yl sulphone, does not allow one to observe any deactivation (Figure 6b, curve 1). It is worth mentioning that cathodic deactivations of acidic substrates in aprotic solvents are rather general in electrochemistry, e.g. aromatic ketones behave rather similarly, showing deprotonation of the substrate by the dianion of the carbonyl compound39. 

The derivative-forming process in pyrolytic alkylation involves two sequential reactions deprotonation of the acidic substrate in aqueous solution by the strongly basic tetra-alkylammonium ion and the thermal decomposition of the quaternary M-alkylammonium salt formed to give a tertiary amine and alkyl derivative. For some weak acids both processes may occur virtually simultaneously in the injector oven of the gas chromatograph. 

The anions of CDs may also function as simple basic catalysts towards acidic substrates included in their cavities. Such was observed by Daffe and Fastrez (1983) who studied the deprotonation and hydrolysis of oxazolones in basic media containing CDs. Also, in a paper dealing mainly with catalysis by amylose, it was noted that CDs catalyse the deprotonation of long chain /3-keto esters in basic aqueous DMSO (Cheng et al., 1985) no saturation kinetics were found for CDs, indicating weak substrate binding under the conditions used. 

This view has been challenged with more recent evidence indicating that AT-[(acyloxy)methyl] derivatives of both primary and secondary amides (8.170, Fig. 8.21) undergo decomposition by the same mechanisms, namely a) an acid-catalyzed process involving protonation followed by formation of an /V-acyliminium species (Fig. 8.21, Reaction a) b) a pH-independent heterolytic cleavage forming the same /V-acyliminium species (Fig. 8.21, Reaction b) and c) a base-catalyzed pathway, which for /V-[(acyloxy)methyl] derivatives of AT-methylamides is the normal mechanism (Fig. 8.21, Reaction c), but for AT-[(acyloxy)methyl] derivatives of primary amides involves substrate deprotonation followed by /V-acy limine formation (Fig. 8.21, Reaction d) [218],... 

The foregoing classification is of fundamental significance for the understanding of enolate chemistry. For every pair of C,H acid and base, one needs to know whether the combination effects quantitative or partial enolate formation. If deprotonation is only partial, then the unreacted substrate may represent an electrophile that can react with the enolate nucleophile. In such a case, it depends on the specific circumstances whether an enolate reacts with any remaining substrate or whether it reacts only with an added different electrophile. The occurrence of a reaction between enolate and unreacted substrate is avoided if the C,H acid is deprotonated completely with a stoichiometric amount of a sufficiently strong base. 

While norbornene, norbornadiene, 2-triallkylsilylnorbornadiene, and 1,3,5-cycloheptatriene are selectively deprotonated by the LIC-NAOR mixture (butyllithium/sodium /f 7-butoxide), other less acidic substrates such as bicyclo[2.2.2]oct-2-ene, camphene, 3,3-dimethyl-l-butene, and tro/o-dicyclopentadiene require the use of stronger bases constituted by mixtures of pentylsodium/disodium pinacolate (NAC-NAOR) or pentylsodium/ potassium ftrt-butoxide (NAC-KOR). 

Greg Kubas of Los Alamos National Laboratory has determined how hydrogen interacts with metals. The important part of his work is that hydrogen, a substrate that is redox inactive substrate and not Brpnsted acidic, transforms upon complexation whereupon the coordinated H2 becomes acidic. The deprotonation of a metal dihydrogen complex generates oxidizable species and in this way, H2 is connected to electrons and heterolytic activation. Rauchfuss explained that Kubas discovery has helped guide his team s effort to connect H2 binding to this redox-active iron metal. 

The y-protons in a,y6-unsaturated nitriles and the a-protons in 6, /-unsaturated nitriles are also acidic, and anionic intermediates may deprotonate such substrate molecules. Thermodynamically these nitriles are more acidic than water (when compared in DMSO) and more acidic than MeCN. This may lead to double-bond isomerizations or oligomerization/polymerization reactions. An example of a base-induced isomerization is the electrolysis of 3-butennitrile in MeCN/HoO (Et4NOTs). The 3-butennitrile is converted into 8a and the LHD of 8a found as the main product [58]. Oligomers formed via substrate deprotonation contain a double bond, since oligomerization is initiated by... 

Those EGBs for which proton-transfer rates are easily measured are radical anions derived by one-electron electrochemical reduction from azobenzenes (Sec. III.A.l), aromatic (Sec. III.C.3), and heteroaromatic hydrocarbons (Sec. III.A.3), and dioxygen (Sec. III.B.l). In those cases the protonated EGB is removed in a fast disproportionation reaction (cf. Sec. II.B, Eq. 2-4), and the proton-transfer step therefore is made effectively irreversible. In CV experiments with addition of an acidic substrate, protonation of the already mentioned radical anions is observed as an increase in the cathodic peak current (change from a one-electron to a two-electron process) and a decrease in the anodic peak current. Where the proton transfer reaction is fast compared to the time scale of the CV experiment, the cathodic peak current is doubled and the anodic peak completely vanishes. If the CV at low scan rates is unchanged after addition of (an excess of) acidic substrate, the EGB is too weak a base to deprotonate the substrate at a reasonable rate. 

The catalytic, enantioselective, vinylogous Mannich reaction has recently emerged as a very powerful tool in organic synthesis for the assembly of highly functionalized and optically enriched 6 amino carbonyl compounds. Two distinctly different strategies have been developed. The first approach calls for the reaction of preformed silyl dienolates as latent metal dienolates that react in a chiral Lewis acid or Bronsted acid catalyzed Mukaiyama type reaction with imines. Alternatively, unmodified CH acidic substrates such as a,a dicyanoalkenes or 7 butenolides were used in vinylo gous Mannich reactions that upon deprotonation with a basic residue in the catalytic system generate chiral dienolates in situ. 

Ru(Tp/pr2)(OH2)(dppe)]OTf reacts with KOH yielding the six-coordinate [Ru(OH)(Tp Pr2)(dppe)]. Deprotonation of [Ru(TpPr2)-(OH2) (bipy)] OTf affords the hydroxo species [Ru( OH)(Tp Pr2) (OH2) -(bipy)]. [Ru(OH)(Tp Pr2)(dppe)] is basic enough to be condensed with acidic substrates such as carboxylic acid. Thus, addition of acetic acid produced the acetato complex [Ru(K1-OAc)(Tp Pr2)(dpPe)]... 

There is an increase in the importance of electrophilic catalysis by zinc cation relative to acetic acid for deprotonation of the a-carbonyl carbons of hydroxyace-tone, a substrate which provides a second stabilizing chelate interaction between the hydroxy group at the substrate and the metal dication that is expressed at transition state for proton transfer [19]. For example, the third-order rate constants kx for the Zn +-assisted acetate-ion-promoted deprotonation of the a-CHs and a-CH20H groups of hydroxyacetone are 32-fold and 770-fold larger, respectively, than the corresponding second-order rate constants kAco for proton transfer to acetate anion assisted by solvent water that is present at 55 M (Scheme 1.12). This shows that Zn + stabilizes the transition state for proton transfer from the a-CHs... 

An attempt to alkylate 3-[(25,4/J)-3-benzoyl-2-ter -butyl-l-methyl-4-oxo-4-imidazolidinyll propanoic acid after deprotonation with lithium diisopropylamide leads to an unexpected result the alkyl group is attached to the base and the substrate is reisolated, but is completely epimerized to 2 ... 

Usually, as the formation of a radical-cation from a neutral substrate is associated with an increase in its acidity, facile deprotonation can take place [6, 7]. In a majority of instances, proton transfer takes place between radical-cation/radical-anion pairs, with the net result being the formation of two radicals and consequently a bimolecular coupling product (Scheme 3). This process is encountered in benzyl radical-cations, olefin radical-cations, and amine radical-cations. 

Scheme 3.20 Deprotonation of acidic substrates by f-element-metal complexes.

Transamination Hydrolysis of the a-carbon-amino bond of the ketimine formed by deprotonation of the a-carbon of the amino acid results in the release of the 2-oxo-acid corresponding to the amino acid substrate and leaves pyridoxamine phosphate at the catalytic site of the enzyme. This is the half-reaction of transamination. The process is completed by reaction of pyridoxamine phosphate with a second oxo-acid substrate, forming an intermediate ketimine, followed by the reverse of the reaction sequence shown in Figure 3, releasing the amino acid corresponding to this second substrate after displacement from the aldimine by the reactive lysine residue to reform the internal Schiff base. 

Apart from the alkylation of deprotonated C-H acidic substrates, such as the a-... 

---