Triethylamine catalysis

The mechanism of the cycloaddition process was partly clarified on the basis of experiments with acetylenic dithio derivatives 102, which were found to be thermally transformable to allenic isomers 103.149 The latter gave expected 2/7-thiopyrans 104 in 41 to 78% yields under triethylamine catalysis, whereas isomeric thiophenes 105 were formed in the presence of protic acids (Scheme 5). The activation energies for some of the processes were also measured.149... 

A more recent synthesis by our group utilized Mukaiyama s trimethylsilyl cyanide addition to aldehydes as the key step to introduce the carboxy functionality [33,36], This approach also required the preparation of (Z)-5-pentadecenal as the key intermediate, Fig. (12). In this case, commercially available decyl aldehyde was coupled with 4-carboxybutyltriphenylphosphonium bromide under Wittig conditions, resulting in a 10 1 mixture of the known (Z)- and ( )-5-pentadecenoic acids. The acids were then reduced to the desired (Z)-5-pentadecenal via (Z)-5-pentadecen-l-ol, a known pheromone. Addition of trimethylsilyl cyanide to (Z)-5-pentadecenal, under triethylamine catalysis, yielded... 

The synthesis of (Z)-2-methoxy-5-hexadecenoic acid (10) was done in a similar fashion, but it first required the preparation of (Z)-4-pentadecenal. In this case, the aldehyde was made starting with commercially available 1-dodecyne that was coupled with 2-(2-bromoethyl)-l,3-dioxolane and n-BuLi in tetrahydrofuran-hexamethylphosphoramide, resulting in the expected 2-(3-tetradecyne)-1,3-dioxolane, Fig. (13). Subsequent catalytic hydrogenation using Lindlar s catalyst afforded the expected 2-(3-tetradecenyl)-l,3-dioxolane. The dioxolane was removed with 5% HC1 in acetone-water (1 1), and the equilibrium favored (Z)-4-pentadecenal. Addition of trimethylsilyl cyanide to (Z)-4-pentadecenal under triethylamine catalysis as described by Mukaiyama for other shorter-chain analogues [36] resulted in 2-trimethylsilyloxy-5-hexadecenonitrile. Under basic conditions the... 

Finally, the stepwise oxidation of the phosphorus atoms in 53a by means of bis(trimethylsilyl) peroxide or by elemental sulfur under triethylamine catalysis should be mentioned these reactions ultimately lead to the tetroxide or tetrasulfide, respectively (53a 68) [15, 58, 59]. 

Bifunctional catalysis in nucleophilic aromatic substitution was first observed by Bitter and Zollinger34, who studied the reaction of cyanuric chloride with aniline in benzene. This reaction was not accelerated by phenols or y-pyridone but was catalyzed by triethylamine and pyridine and by bifunctional catalysts such as a-pyridone and carboxylic acids. The carboxylic acids did not function as purely electrophilic reagents, since there was no relationship between catalytic efficiency and acid strength, acetic acid being more effective than chloracetic acid, which in turn was a more efficient catalyst than trichloroacetic acid. For catalysis by the carboxylic acids Bitter and Zollinger proposed the transition state depicted by H. 

Bifunctional catalysis has also been observed by Pietra and Vitali35 for a more typical nucleophilic aromatic substitution reaction, that of 2,4-dinitrofluorobenzene and piperidine in benzene. For this reaction triethylamine does not have an... 

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. 

Ligand to rhodium ratio is 10, catalysis performed in 13 ml of toluene using 1 ml of 1-octene as the substrate at 80 °C and 50 bar CO/H2. Samples were analysed by means of GC and GC-MS analysis. b Average turnover frequencies were calculated as (mol product)(mol catalyst)1 h 1.c 1 ml of 1-propanol added to the catalyst mixture 1 Initial turnover frequency. 1 ml of triethylamine added to the catalyst mixture. 

Based on nucleophilic addition, racemic allenyl sulfones were partially resolved by reaction with a deficiency of optically active primary or secondary amines [243]. The reversible nucleophilic addition of tertiary amines or phosphanes to acceptor-substituted allenes can lead to the inversion of the configuration of chiral allenes. For example, an optically active diester 177 with achiral groups R can undergo a racemization (Scheme 7.29). A 4 5 mixture of (M)- and (P)-177 with R = (-)-l-menthyl, obtained through synthesis of the allene from dimenthyl 1,3-acetonedicar-boxylate (cf. Scheme 7.18) [159], furnishes (M)-177 in high diastereomeric purity in 90% yield after repeated crystallization from pentane in the presence of catalytic amounts of triethylamine [158], Another example of a highly elegant epimerization of an optically active allene based on reversible nucleophilic addition was published by Marshall and Liao, who were successful in the transformation 179 — 180 [35], Recently, Lu et al. published a very informative review on the reactions of electron-deficient allenes under phosphane catalysis [244]. 

Okamura and coworkers151 studied the base catalyzed Diels-Alder reactions between 3-hydroxy-2-pyrone (224) and chiral l,3-oxazolidin-2-one based acrylate derivatives. Catalysis of the reaction between 224 and 225 by triethylamine gave fair to good de values, somewhat dependent on the solvent system used (equation 63, Table 7). Addition of 5% of water to the solvent isopropanol, for example, increased the de of the endo adduct 226 substantially. When the amount of water was increased, however, the triethylamine catalyzed reaction became less endo and diastereofacially selective, a small amount of exo 227 being obtained. Replacing triethylamine by the chiral base cinchonidine also improved the de, but now independently of the solvent system used. 

Examples of possible intramolecular general acid-base catalysis were reported by Kupchan et al. (1962). The methanolysis of coprostanol acetate and coprostane 3/3, 5/3-diol 3-monoacetate [12] in aqueous methanol was conducted in triethylamine-triethyl-ammonium acetate buffer. The rates of methanolysis at constant... 

In acid catalysis (HCl), the variation in pH of the medium affects the yield of oligoorganylsilsesquioxanes to a lesser extent than in the case of alkaline catalysis. Base catalysts are used in the synthesis of oligosilsesquioxanes mainly in the thermolysis of the primary products of XSiYj hydrolysis (Table 1). The most efficient catalysts, in this case, are those which are readily decomposed upon heating to give inactive products For example, the use of tetraethylammonium 32,45) trimethyl-benzyl ammonium 23.37,41) triethylamine hydroxides has proved successful. 

An unusual example of oxazoline formation is illustrated in the following example in which the hydroxyl moiety is masked as a tetrahydrofuran ring. Depending on reaction conditions, regioselective ring closure to one of the two oxazolines can be realized. Thus, addition of methanesulfonyl chloride to a mixture of substrate and EtsN resulted in the expected oxazoline 46. On the other hand, addition of < 1 equiv of triethylamine to a mixture of substrate and methanesulfonyl chloride, followed by acid catalysis produced oxazoline 47. Intermediate 47, obtained in 72% overall yield from 45, was susequently converted to the human immunodeficiency virus (HlV)-protease inhibitor Nelfinavir 48 (Scheme 8.18). 

The synthesis of phosphino sulfoximine 97 relied significantly on the successful development of methods pursued in parallel in our group. Whereas palladium-catalyzed cross-couplings between 53 and 98 proceeded in low yield, the copper catalysis with a combination of copper(l) iodide and cesium acetate worked well, affording 99 in up to 83% yield [78]. The resulting phosphine oxides 99 were then reduced to the corresponding phosphines 97 using a mixture of trichlorosilane and triethylamine (Scheme 2.1.1.33). 

Catalysis by triethylamine in similar processes was recognized in the case of two regioisomeric dienones 129 and 131, which isomerized to 2//-pyran 130.174... 

Huisgen, Szeimies, and Mobius have studied the addition reactions of aryl azides to a,/S-unsaturated esters and nitriles.1 4 Methyl acrylate (73) reacts with aryl azides to form l-aryl-4-carbomethoxy-A -triazolines in agreement with the orientation rule based on electronic effects. These A -triazolines are completely converted by base catalysis into the ring-opened isomer. Thus l-phenyl-4-carbomethoxy-A2-triazo ine (74) gives, in the presence of triethylamine at room temperature, methyl 3-aniline-2-diazopropionate (75). The A2-triazolines as well as the a-diazoesters are thermolabile. 74 is converted into l-phenyl-2-carbomethoxyaziridine (76) and 75 gives methyl 3-anilinoacrylate (77) as thermolysis product.262... 

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