Iminium-2-carboxylate

B188) and the realization that the oxidative desamination of amino acids 4 proceeds via 5 by a sequence involving the decarboxylation of an iminium-2-carboxylate (6 7), followed by desamination (7 8)... 

As a matter of fact, the iminium-2-carboxylate 6 is the model of a partial stmcture of hetarenium-carboxylates 9—14 which have proved to be versatile starting materials for the generation of NHCs 15—20 (vide infra) (Scheme 5). 

Furthermore, (L)-proline and paraformaldehyde give (L)-N-hydroxymethyl-proline (as the iminium carboxylate -i- H2O) upon large scale milling and stoichiometric millings of imidazole (0 °C) or benzimidazole (r. t.) with (HCHO) quantitatively provide the corresponding solid 1-imidazolylmethanols [22]. 

Figure 2 illustrates the formation of 5-acetyl-7-methyl-[iv], 5-acetyl-6-methyl-[v], 7-formyl-5-methyl-[vi] and [vii] 7-acetyl-5-methyl-2,3-dihydro-(lH)-pyrrolizines after Tressl et al. (5). The 2,3-dihydro-(lH)-pyrrolizines require both carbohydrate fragmentation products and proline for their formation. Both the 5-acetyl- pyrrolizines [iv] and [v] increased in quantity as the reaction temperature increased while [vi] and [vii] were found at maximum quantity at 152.5°C. The first pair are formed through an iminium carboxylate intermediate which is decarboxylated into an exocyclic iminium ion which then undergoes an aldol... 

The 7-formyl- and 7-acetyl- pyrrolizines are formed by an iminium carboxylate intermediate followed by decarboxylation to the cyclic iminium ion which underwent nucleophilic addition followed by aldol ring closure. This pathway accounts for the 7-formyl-5-methyl [vi] and 7-acetyl-5-methyl [vii] depending if the iminium addition is by OHCCH2OH or CH3COCH2O. 

During investigations on the carbonyl-assisted decarboxylation of N-alkylated ot-amino acids, Rizzi found that azomethine ylide intermediates are involved in the decarboxylative condensation (70JOC2069). Heating sarcosine and benzophenone at 170°C (or benzaldehyde at 150-170°C) gave 3-methyl-2,2,5,5-tetraphenyloxazolidine, which corresponds to the cycloadduct of azomethine ylide 98 to the carbonyl compound. This sequence may involve the initial formation of iminium carboxylate betaines and subsequent decarboxylation to generate nonstabilized azomethine ylides [Eq. (15)]. This... 

In the end, the stereochemistry of the reacting dipole is determined by the relative rates of the reversible ring closure of the iminium carboxylate betaine into 2,4-trans-5-oxazolidines (kj), the decarboxylative ylide generation (kj), the isomerization of anti-ylides into syn-ylides (kj), and cycloaddition trappings 1(4 and kj), as shown in Eq. (23). 

The piperazine cocatalyst seemed to act as a counter cation to the iminium carboxylate in the transition state thus leading to higher enantioselectivities [157,158],... 

Moyano, Rios, and co-workers [38] have shown that the beneficial effect of hydrogen-bond donors in proline-catalyzed aldol reactions in nonpolar solvents [39] is due both to the facilitation of proline solubilization by formation of an oxazolidinone with the ketone and to the stabilization of the iminium carboxylate zwitterionic form that is the direct precursor of the reactive enamine intermediate,... 

Step 2 of Figure 29.11 Decarboxylation The TPP addition product, which contains an iminium ion j8 to a carboxylate anion, undergoes decarboxylation in much the same way that a jB-keto acid decarboxylates in the acetoacetic ester synthesis (Section 22.7). The C=N+ bond of the pyruvate addition product acts... 

Eq. 25) [295]. A similar mechanism has also been proposed for the electrolysis of isobutyric and pivalib acid in acetonitrile [296]. As the intermediate alkyl cation can rearrange and the intermediate iminium cation can furthermore react with the starting carboxylic acid three different amides can be isolated (Eq. 26) [295 a]. The portion of the diacylamide can be considerably increased if the electrolyte consists of acetonitrile/ acetic acid [295 b]. 

A catalytic mechanism, which is supported by deuterium-labeling experiments in the corresponding Ru-catalyzed procedure [146], is shown in Scheme 47. Accordingly, the reactive Fe-hydride species is formed in situ by the reaction of the iron precatalyst with hydrosilane. Hydrosilylation of the carboxyl group affords the 0-silyl-A,0-acetal a, which is converted into the iminium intermediate b. Reduction of b by a second Fe-hydride species finally generates the corresponding amine and disiloxane. 

Iminium Acyl Aldehyde Ester Amide Carboxylate Group 111... 

Appropriate activation of carboxyl groups enables reduction of aliphatic carboxylic acids to the corresponding aldehydes. The electroreduction of iminium salts prepared from aliphatic carboxyKc... 

The anodic lactonization of a 2-pipe-ridinone carboxylic acid (Scheme 28) [39] results from a coupling reaction between the nucleophilic carboxylate and the electrogenerated iminium intermediate. 

Irradiation of matrix-isolated imidazole-2-carboxylic acid gave the 2,3-dihydro-imidazol-2-ylidene-C02 complex (31) characterized by IR spectroscopy and calculated to lie 15.9 kcal mol above the starting material. A series of non-aromatic nucleophilic carbenes (32) were prepared by desulfurization of the corresponding thiones by molten potassium in boiling THF. The most hindered of the series (32 R = Bu) is stable indefinitely under exclusion of air and water and can be distilled without decomposition. The less hindered carbenes slowly dimerize to the corresponding alkenes. Stable aminoxy- and aminothiocarbenes (33 X = O, S) were prepared by deprotonation of iminium salts with lithium amide bases. The carbene carbon resonance appears at 260-297 ppm in the NMR spectrum and an X-ray structure determination of an aminooxycarbene indicated that electron donation from the nitrogen is more important than that from oxygen. These carbenes do not dimerize. 

Hine has demonstrated that simple amino acids, such as glycine and p-alanine, are not capable of intramolecular deprotonation in the reaction with isobutyraldehyde-2-d (Scheme 8) [62], Apparently, the carboxylate moiety in the iminium ion intermediate 29 is a relatively weak base and, as such, external bases, present in the buffer used (e.g. acetate ions), are largely responsible for the formation of the enamine intermediate 30. 

In a series of reports between 1991 and 1997 Yamaguchi showed that rubidium salts of L-proline (9) catalysed the conjugate addition of both nitroalkanes [29, 30] andmalonates [31-33] to prochiral a,p-unsaturated carbonyl compounds in up to 88% ee (Scheme 1). Rationalisation of the selectivities observed involved initial formation of an iminium ion between the secondary amine of the catalyst and the a,p-unsaturated carbonyl substrate. Subsequent deprotonation of the nucleophile by the carboxylate and selective delivery using ion pair... 

The 6//-l,3-thiazin-6-iminium hydroperchlorate salts 78-81 give interesting products when treated with nucleophiles <2003H(60)2273>. Hydrolysis of 6-imino-6//-l,3-thiazine hydroperchlorate 78 affords (2Z,4Z)-2-cyano-5-hydroxy-5-phenyM-azapenta-2,4-dienethioamide 82 in excellent yield, while treatment with morpholine gives 2-(morpholinomethylene)malononitrile 83 and thiobenzamide. The 5-(ethoxycarbonyl) -(methylthio)-2-aryl-6/7-l,3-thiazin-6-iminium salts 79 and 80 react with hydroxide or morpholine to afford ethyl 4-(methylthio)-2-aryl-6-thioxo-l,6-dihydropyrimidine-5-carboxylates 84 and 85. In the case of the 4-chloro analogue 80, the (Z)-ethyl 2-(5-(4-chlorophenyl)-37/-l,2,4-dithiazol-3-ylidene)-2-cyanoacetate 87 is also formed for the reaction with sodium hydroxide. The 1,2,4-dithiazoles 86 and 87 can be obtained as the sole product when 79 and 80 are treated with sodium acetate in DMSO. Benzoxazine 88 is isolated when the iminium salt 81 is treated with morpholine or triethylamine. Nitrile 89 is formed as a ( /Z)-mixture when 6-imino-67/-l,3-thiazine hydroperchlorate 79 is reacted with triethylamine and iodomethane in methanol <2003H(60)2273>. 

Hence, if the proline-catalyzed aldol reaction between acetone and 4-nitrobenzal-dehyde in DM SO is carried out using 5 mol% proline, decarboxylation occurs and [3 + 2] cycloaddition between the resulting ylide and benzaldehyde gives a 1,3-oxazolidinone as the maj or side product [98]. Therefore, it is important that if catalyst loadings are to be reduced, either the carboxylic acid should be unable to decarbox-ylate (e.g. Appendix 7.B, Entries 12 [97, 98], 35 [99]) or else must be replaced by an isostere [101, 102] (e.g. Appendix 7.B, Entries 7 [103, 104], 8-10 [105], 11 [106], 28 [107]). Alternatively, the relative rate of the aldol reaction can be increased in order to minimize the concentration of iminium ion in solution and remove it from equilibrium before decarboxylation can take place. 

RCOOH — RCHO. The iminium salt (1) formed on reaction of a carboxylic acid with the Vilsmeier reagent (formed from DMF and oxalyl chloride) is reduced by lithium tri-/-butoxyaluminum hydride (1 equiv.) to an aldehyde. The chemo-selectivity is noteworthy ester, nitrile, keto, and halide groups are not affected.3... 

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