Halides, aliphatic catalyst effect

Employing protic and halide additives can effectively reverse the deleterious effect with aliphatic amines [8, 11]. The optimum results are obtained when ammonium iodide is employed as the addihve in combination with the second-generation rhodium-iodide catalyst. Under these conditions, a variety of aliphatic amines can be used to generate the aminotetrahn products in high yields and with excellent enantiomeric excess (Scheme 9.4). From a technical perspective, ammonium iodide benefits from being a combined proton and iodide source that is air-stable and nonhygroscopic. 

Further invention of pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI) ligands has led to a remarkable improvement in palladium-catalyzed C—S coupling [159, 160]. This catalyst effectively couples the less reactive aryl chlorides even at room tempauture [161]. Recently, NHC-based catalyst, [Pd(IPr )(cin)Cl] 18, has been developed for the coupling of aryl halides with aliphatic or aromatic thiols (Scheme 20.53) [162]. 

Martin, Padron, and coworkers have reported on the scope and limitations of the use of iron(lll) halides as effective catalysts in the coupling of alkenes or acetylenes with aldehydes to achieve a wide variety of useful synthetic transformations. All these reactions are shown in Scheme 10, which serves as a guide through the aliphatic C-C bond formation section [27]. 

The use of heterogeneous catalysts in the synthesis of urethanes from aliphatic and aromatic amines, C02 and alkyl halides has been explored only recently. Titanosilicate molecular sieves [60a], metal phthalocyanine complexes encapsulated in zeolite-Y [60a], beta-zeolites and mesoporous silica (MCM-41) containing ammonium cations as the templates [60b, c], and adenine-modified Ti-SBA-15 [60d, e] each function as effective catalysts, even without any additional base. 

Aryl chlorides are more reluctant to participate in amination than most other aryl halides/pseudohalides. To tackle this problem, Caddick et al. examined the effect of palladium-N-heterocyclic carbenes as catalysts in rapid microwave-promoted reactions [87]. Para-tolyl and -anisyl chloride were reacted with aromatic and aliphatic amines in mostly good yields within 6 minutes of heating at 160 °C. Reactions using anisyl, tolyl or phenyl chlorides and aliphatic amines have also been reported by Maes et al. using a phosphine ligand and a strong base, which creates the desired products after 10 minutes of heating at 110-200 °C [88]. 

Reactive halogen compounds such as benzyl chloride, 2-thenyl chloride, 2-bromoacetylthiophene, (C HjS)COCH,Br , and 2-chloromethyl-thianaphthene (C,H5S)CHjCl are readily converted to esters by treatment with the sodium salts of carboxylic acids. A small amount of tri-ethylamine has proved to be an effective catalyst. Acetates are oftentimes made by heating halides with fused sodium acetate in glacial acetic acid, e.g., p-ethylbenzyl acetate (93%). The reaction is of little value for the preparation of simple aliphatic esters. Secondary and tertiary halides give increasing amounts of olefin by dehydro-halogenation. 

Alkanesulfonic acids can be prepared from the thiols or disulfides and air using cocatalytic DMSO and HBr.f The use of aqueous DMSO in the absence of air, but in the presence of a halogen or hydrogen halide catalyst, readily converts most aliphatic, aromatic, and heterocyclic thiols or disulfides to the corresponding sulfonic acid. In effect, DMSO oxidizes the hydrohalide to the molecular halogen, which then reacts with the organosulfur substrates. Water serves as a proton and oxygen source, and inhibits the Pummerer-type decomposition of the DMSO. 

The most interesting series of observations in this field have been made on the catalytic action of Lewis acids, which are also effective catalysts of Diels-Alder reactions (Section 4.1.6). In the presence of BF3 or its derivatives it has been possible to obtain 1,3-cycloadditions that do not proceed under uncatalysed conditions, e.g. those of benzonitrile oxide to aliphatic nitriles and carbonylic compounds and to oximes . The method has been applied also to the cycloaddition of diazomethane to CN multiple bonds, by using alkyl aluminium halides . Lewis acid catalysts probably act by making the dipolarophiles more polar, through complexing. 

The Group VIB arene-metal tricarbonyl complexes are effective homogeneous catalysts for the dehydrohalogenation of aliphatic alkyl halides to create an olefin function [17]. Often mixtures of several isomers occur in these reactions with terminal alkenes being formed as the major product (Scheme 5). This suggests that the proportion of products depends on their relative rate of formation (kinetic control). 

The low ionic character of the aluminium-silicon bond has been cleverly utilized to develop a very mild, general and effective synthesis of acyl silanes, successful for aliphatic, aromatic, heteroaromatic, a-aUcoxy, a-amino and even a-chiral and a-cyclopropyl acyl sUanes. Acyl chlorides are treated with lithium tetrakis(trimethylsilyl)aluminium or lithium methyl tris(trimethylsilyl) aluminium in the presence of copper(I) cyanide as catalyst to give the acyl silanes in excellent yields after work-up. Later improvements include the use of 2-pyridinethiolesters in place of acyl halides, allowing preparation of acyl silanes in just a few minutes in very high yields indeed (Scheme 9) °, and the use of bis(dimethylphenylsilyl) copper lithium and a dimethylphenylsilyl zinc cuprate species as nucleophiles. 

The ability of bismuth(III) nitrate pentahydrate as effective catalyst in the Biginelli reaction was reported, while the oxidative property of this salt has been also investigated. By combining both of these characteristics, the authors developed a convenient alternative method for the Biginelli reaction. The direct synthesis of 3,4-dihydropyrimidin-2(lH)-ones by three-component condensation in one pot, using benzyl halides in place of aldehydes in the presence of bismuth nitrate pentahydrate in tetrabutylammonium fluoride (TBAF), afforded the products in good to excellent yields. Some chemoselectivity was observed, the aliphatic halides gave less than 30% of the respective dihydropyrimidinones under the present reaction conditions (Equation 12) [33a]. 

Abstract This review covers the recent recyclable protocols for the C-N bond forming reactions between aromatic, heterocyclic and aliphatic amines such as imidazoles, benzimidazoles, benzylamines, piperidine, pyrrole, imides, anilines, hexyl, cyclohexyl amines, and amides as coupling partners with aryl iodides, bromides, chlorides, and arylboronic acids employing copper-mediated systems. The physical properties and characterization of the catalysts and their use in organic synthesis will be outlined. Most importantly, these recyclable versions developed by many groups in the recent years are potential candidates for commercial exploitation. The effect of additives, solvents, temperature, base, the nature of aryl halides on reactivity, and recycle studies of the heterogeneous catalysts are included in this... 

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