Activated carboxylates, catalytic

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

A key step in the synthesis of 13-membered meta ansa and 14-membered para ansa peptide alkaloids involves catalytic hydrogenolysis of carbobenzyl-oxypeptide pentafluorophenyl esters. The most suitable solvent is dioxane with addition of a catalytic amount of pyrrolidinopyridine and 2% ethanol. Temperature should not exceed 90°C. The authors believe that after deblocking, the amino function remains on the surface until ring formation with the activated carboxylic function is accomplished (/5/). 

Compound A, C/H, was found to be optically active. On catalytic reductior over a palladium catalyst, 2 equivalents of hydrogen were absorbed, yielding compound B, CyH. On ozonolysis of A, two fragments were obtained. One fragment was identified as acetic acid. The other fragment, compound C, wa an optically active carboxylic acid, C5Hl002- Write the reactions, and drav structures for A. B and C. 

The second step, nucleophilic attack of an alcohol or phenol on the activated carboxylic acid RCOIm (carboxylic acid imidazolide), is usually slow (several hours), but it can be accelerated by heating[7] or by adding a base[8] [9] such as NaH, NaNH2, imidazole sodium (ImNa), NaOR, triethylamine, diazabicyclononene (DBN), diazabicycloimdecene (DBU), or /7-dimethylaminopyridine to the reaction mixture (see Tables 3—1 and 3—2). This causes the alcohol to become more nucleophilic. Sodium alcoholate applied in catalytic amounts accelerates the ester synthesis to such an extent that even at room temperature esterification is complete after a short time, usually within a few minutes.[7H9] This catalysis is a result of the fact that alcoholate reacts with the imidazolide very rapidly, forming the ester and imidazole sodium. 

The proposed catalytic cycle for this reaction begins with the initial attack of the in situ generated thiazolylidene carbene on the epoxyaldehyde followed by intramolecular proton transfer (Scheme 28, XXXII-XXXIII). Isomerization occurs to open the epoxide forming XXXIV which undergoes a second proton transfer forming XXXV. Diastereoselective protonation provides activated carboxylate intermediate XXXVI. Nucleophilic attack of the activated carboxylate regenerates the catalyst and provides the desired P-hydroxy ester. 

Recently, Bode et al. were able to demonstrate that the products formed after generation of the homoenolate equivalents 67 are determined by the catalytic base [64]. Strong bases such as KOt-Bu led to carbon-carbon bond-formation (y-butyrolactones), while weaker bases such as diisopropylethylamine (DIPEA) allowed for protonation of the homoenolate and the subsequent generation of activated carboxylates. The combination of triazolium catalyst 72 and DIPEA in THF as solvent required no additional additives and enabled milder reaction conditions (60 °C), accompanied by still high conversions in the formation of saturated esters out of unsaturated aldehydes (Scheme 9.21). Aliphatic and aromatic enals 62, as well as primary alcohols, secondary alcohols and phenols, are suitable substrates. a-Substituted unsaturated aldehydes did not yield the desired products 73. 

The broad scope of the catalytic generation of activated carboxylates was demonstrated by Bode et al. in the diastereoselective synthesis of / -hydroxy esters 79 from a,/ -epoxy aldehydes 80 employing achiral thiazolium salts 81 as precatalysts (Scheme 9.24) [67]. The incorporation of a reducible functionality into the aldehyde substrate is the premise for a catalyst-induced intramolecular redox reaction generating the activated carboxylate 82. 

Chow KYK, Bode JW (2004) Catalytic generation of activated carboxylates direct, stereoselective synthesis of fi-hydroxyesters from. J Am Chem Soc 126 8126-8127... 

Sohn SS, Bode JW (2005) Catalytic generation of activated carboxylates from enals a product-determining role for the base. Org Lett 7 3873-3876... 

A new type of latent-active glycosyl donors, 2 -carboxybenxyl glycosides and their benzyl esters, have been recently introduced [62-64]. The active carboxylic acids are readily available from the latent benzyl esters by catalytic hydrogenation in the presence of ammonium acetate. In an example [62] shown in Scheme 5.24 the latent mannoside (136) was glycosylated with the active donor (135) to provide exclusively the p-linked disaccharide (137) in excellent yield. The latent... 

The Bode group have documented an NHC-catalyzed enantioselective synthesis of ester enolate equivalents with a,p-unsaturated aldehydes as starting materials and their application in inverse electron demand Diels-Alder reactions with enones. Remarkably, the use of weak amine bases was crucial DMAP (conjugate acid = 9.2) andN-methyl morpholine (NMM, conjugate acid pAa = 7.4) gave the best results. A change in the co-catalytic amine base employed in these reactions could completely shift the reaction pathway to the hetero-Diels-Alder reaction, which proceeded via a catalytically generated enolate. An alternative pathway that occurred via a formal homoenolate equivalent was therefore excluded. It is demonstrated that electron-rich imidazolium-derived catalysts favor the homoenolate pathways, whereas tri-azolium-derived structures enhance protonation and lead to the enolate and activated carboxylates (Scheme 7.71). 

In crosslinking reaction of polyacrylic elastomer which contains carboxyl and epoxy groups as cure-sites by onium salt catalyst, the effective center is an active carboxylate onium salt. The catalytic activity showed good agreement with the nucleophilicity of the counter anion of onium salt and followed I > Br > Clo... 

Once bicarbonate has been activated, the catalytic reaction can begin. The mechanism for the carboxylation of acetyl CoA is shown next. 

Our first reaction protocol proved to be broadly applicable with regard to aryl bromides, but only in combination with 2-nitrobenzoic acid and a few other highly activated carboxylic acids (Scheme 9). It was a decisive first step, but failed to fulfill my high expectations. I will never forget the face of Dr. Deng when I told him that I did not yet want to pubhsh the results of his meanwhile more than 1,200 reactions. I did not want to draw the attention of big research groups to this concept until our two-man team had achieved the next critical step and made the reaction catalytic also with regard to the decarboxylation catalyst. Fortunately, we did not know that despite all our mechanistic considerations, this would require another 800 experiments. 

Since these initial reports, the NHC-catalyzed generation of activated carboxylates from a-functionalized aldehydes has been extended to a remarkably wide range of substrate classes. Bode first reported the generation of activated carboxylates from a,p-unsaturated aldehydes as part of his work on the catalytic generation of homoenolates vide infra) These studies were further explored to develop improved catalysts and render this a general process. This work, which identified the uniquely high reactivity of A-mesityl substituted triazolium pre-catalysts as superior to all other catalyst classes for NHC-catalyzed redox reactions of a,p-unsaturated aldehydes, was crucial to the development of the remarkable annulation reactions described below. Zeitler reported analogous... 

Scheme 14.5 Catalytic generation of activated carboxylates (DIPEA = A, Af-diisopropylethylamine).

Consideration of the reaction pathways shown in Scheme 14.12 for the NHC-catalyzed generation of activated carboxylates from enals reveals the intermediacy of an NHC-bound ester enol or enolate equivalent that could be trapped by a suitable electrophile. This was first achieved by Bode, who in 2006 reported highly enantioseleetive inverse electron-demand Diels-Alder reactions of the catalytically generated enolate equivalents and ot,p-unsaturated N-sul-fonyl imines (Scheme 14.19). At the time, this was the first report of a highly... 

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