Deprotonation reactions

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. 

Pyrroline-A-oxide (258) is isomerized into y-lactam (259) in the presence of lithium diisopropylamine (LDA) (470) and sodium trityl (471). In these reactions, deprotonation at C3 occurs, leading to carbanion (260). Then oxygen migration from Ni to C2 takes place via intermediate formation of oxaziridine... 

Fig. 2.2.2.2 Postulated model of the active site of phosphonopyruvate decarboxylase. PPD from Str. viridochromogenes T0494 (based on the structure of PDC from Zymomonas mobilis [27] and data from analyis of site-directed mutants [25]). The model depicts the start of the catalytic reaction (deprotonation of the reactive C2 atom (yellow) on the thiazolium ring ofThDP...

OH, i z X H + H MP2/6-31 ( // MP2/6-31G Geometry, energy, frequency, proton affinity of H2COH+, isodesmic reaction, deprotonation barrier, IGLO-II and GIAO-MP2 NMR chemical shifts 48,50,51,52... 

The cyclic disulfone, 1,3-dithietane 1,1,3,3-tetraoxide 83, underwent Knoevenagel and substitution reactions to form a new class of unsaturated disulfenes. Thus, its treatment with isobutyraldehyde in the presence of a catalyst gave 84 bearing unsaturated vinylic moieties, the double bonds of which were resistant to all typical olefin reactions. Deprotonation of 84 and subsequent silylation with C4F9-S02-0SiMe3 yielded 2,4-disilylated product 85 (Scheme 9) <1996CB161>. 

The bulky ligands PPh3 and AsPh3 add to the unsubstituted end of 31 (180,181). The resulting phosphonium salt (32) is deprotonated by butyllith-ium at — 78°C to yield an ylid (33) which reacts with aldehydes in a Wittig reaction. Deprotonation with potassium tert-butoxide followed by addition of aldehyde 34 gives the E isomer (35) only [Eq. (20)] (182). Trimethylphosphite... 

Tab. 13.4 Thermochemistry of Selected Acid/Base Reactions Deprotonation Enthalpies (kcal/mol) for Deprotonations of /PrOH with Various Organolithium Compounds and Lithium Amides...

We should include the somewhat similar cyclisation onto a phosphine oxide here, even though no carbonyl group is involved. In this strange reaction, deprotonation of 88 a to phosphorus protects this position while halogen-metal exchange generates an aryllithium which displaces PhLi from phosphorus to give 89.50... 

Reverse reaction Deprotonation, followed by loss of the nucleophile. 

Phenyl vinyl sulfide possesses a number of synthetically useful attributes. It participates as an electron-rich alkene in 1 +2,2 2+2,3 3+2,4 and 4+25 cycloaddition reactions. Deprotonation of phenyl vinyl sulfide with strong base affords an a-metallated sulfide that reacts with electrophiles.6 The metallation-electrophile sequence and the cycloaddition reactions afford products amenable to further synthetic manipulation via the sulfide functionality. Furthermore, phenyl vinyl sulfide is a convenient precursor to the synthetically useful phenyl vinyl sulfoxide and phenyl vinyl sulfone.7... 

Although Bronsted proton transfer reactions appear to belong to a unique category not described by Scheme 14, they are examples of polar-group transfer reactions and are not different in principle from nucleophilic displacement reactions. Deprotonation by hydroxide ion can be regarded as the shift of an electron from HO to the Bronsted acid synchronously with the transfer of a hydrogen atom from the Bronsted acid to the incipient HO- radical, with the reaction driven by covalent bond formation between the HO- radical and the H- atom to form water (equation 161). 

Alkylation of pseudoephedrine a-fluoropropionamide can be used to prepare enantiomerically enriched tertiary alkyl fluoride centers (eq 27). In contrast to the alkylation of pseudoephedrine a-fluoroacetamide, alkylation of pseudoephedrine a-fluoropropionamide proceeds with high diastereoselectivity when LDA in used as the base in the reaction and low diastereoselectivity when LHMDS is used. In these reactions, deprotonation of pseudoephedrine a-fluoropropionamide with LDA, proposed to occur under kinetic control, is believed to form the corresponding... 

The first step is an aldol reaction Deprotonation of methyl acetate by LDA is followed by addition to the aldehyde 16, affording ester 28 as a diastereomeric mixture in a ratio of-2 1. 

In 1978, Larcheveque and coworkers reported modest yields and diastereoselectivities in alkylations of enolates of (-)-ephedrine amides. However, two years later, Evans and Takacs and Sonnet and Heath reported simultaneously that amides derived from (S)-prolinol were much more suitable substrates for such reactions. Deprotonations of these amides with LDA in the THF gave (Z)-enolates (due to allylic strain that would be associated with ( )-enolate formation) and the stereochemical outcome of the alkylation step was rationalized by assuming that the reagent approached preferentially from the less-hindered Jt-face of a chelated species such as (133 Scheme 62). When the hydroxy group of the starting prolinol amide was protected by conversion into various ether derivatives, alkylations of the corresponding lithium enolates were re-face selective. Apparently, in these cases steric factors rather than chelation effects controlled the stereoselectivity of the alkylation. It is of interest to note that enolates such as (133) are attached primarily from the 5/-face by terminal epoxides. ... 

The reverse reaction, deprotonation of a vanadium hydride complex to produce an anion, is known. Thus, V(CO)4L2H (L2 = a chelating diphosphine" or diarsine ligand) can be converted to [V(CO)4L2] with OH or NEts. (t -l,3,5-Me3C6H3)V(CO)3H can also be deprotonated with hydroxide ion . 

In the aldol reaction the nucleophilic ketone is first converted into an enol by protonation and deprotonation. The enol then adds to the protonated ketone in an aldol reaction. Deprotonation of the positively charged O gives the aldol. 

Direct metallation. Direct C-H metallations are of several types, of which the most important is reaction ( deprotonation ) with a strongly basic reagent, usually a lithium compound, but is also possible for magnesium and zinc. Electrophilic metallation can be carried out with palladium(II) and mercury(II) salts, and neutral C-H insertion by other transition metals is becoming increasingly important, usually for catalytic reactions. 

An unusual case of internal proton return in a highly chirotopic environment was reported for the L-alanine derivative ( + )-2. On deprotonation with less than one equivalent of LDA in the presence of lithium bromide, and alkylation with iodomethane, 3 is isolated in which the methyl group has entered the ring from the less hindered side (sec also Section 2.1.4.2.). However, complete epimerization of the side chain occurred during this alkylation reaction. Deprotonation first produces the ester enolate. This enolate is selectively reprotonated from the less hindered side by internal proton transfer which produces the starting material for the alkvla-tiony5a. 

Whereas reactions with dimethylacetamide often give poor yields, those with dimethylbenzamide generally are quite successful. An important side reaction, deprotonation of the reagent by RM, may be favoured by high kinetic basicity of RM (e.g. M = K) or the presence of a strongly polar solvent, such as HMPT. 

Usually, the formation of radical cation from a neutral substrate is associated with the increase in its acidity [14,15] and, therefore, facile deprotonation processes may be expected as the common step from some of these intermediates. In majority of instances, the proton transfer takes place between radical cation/ radical anion pairs, with the net result being the bimolecular coupling product. However, during sensitized PET reactions, deprotonation from radical cation is associated either with unilateral radical reactions or their further oxidation to produce carbocationic species [7]. Normally, the rate of proton transfer depends on the kinetic acidity of the cation radical and the basicity of the anion radical. 

Reductive amination with formaldehyde and sodium cyanoborohydride provides a convenient method for methylation of a secondary amine (or dimethylation of a primary amine). An alternative procedure uses formaldehyde together with formic acid (HCOOH) as the source of hydride in what is termed the Eschweiler-Clark reaction. Deprotonation of formic acid provides the formate anion, which delivers hydride to the iminium ion with concomitant formation of carbon dioxide. 

Shibasaki developed the first catalytic enantioselective hydropho-sphonylation of aldimines with the use of chiral heterobimetallic lantha-num(iii) potassium(i) tris(binaphtholate) 89, which provides optically active a-amino phosphonates with high enantioselectivities (Scheme 2.50). Similar to lithium catalyst 26 and sodium catalyst 67, potassium catalyst 89 acts as an acid-base bifunctional catalyst to activate both nucleophiles and electrophiles. In particular, in this reaction, deprotonation of dimethyl phosphite by more basic potassium catalyst 89 was essential for increasing the reactivity and enantioselectivity, while less basic lithium catalyst 26 and sodium catalyst 67 were not effective. 

The kinetically controlled reactions Deprotonation 1 and Deprotonation 2 are discussed in the next section, and the thermodynamically controlled reactions Epimerization 1 and Epimerization 2 in the following section. The third section deals with selective reactions, starting with title compound. The focus will be particularly on this lithiated (aminomethyl)benzylsilane (R,S)-2, whose synthesis, stability of configuration and further transformations (stereochemical course) have been investigated thoroughly. 

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