Alkylation reactions polymer-supported

Moberg et al. [146] modified further the bis(pyridylamide) ligand described by Trost for the preparation of a polymer-supported pyridylamide (113 in Scheme 60) for the microwave-accelerated molybdenum-catalyzed al-lylic alkylation. TentaGel resin was tested in the presence of high concentrations of reactants and gave, after a 30 min reaction, total conversion in the... 

Another example where PEG played the role of polymeric support, solvent, and PTC was presented by the group of Lamaty [72]. In this study, a Schiff base-proteded glycine was reacted with various electrophiles (RX) under microwave irradiation. No additional solvent was necessary to perform these reactions and the best results were obtained using cesium carbonate as an inorganic base (Scheme 7.64). After alkylation, the corresponding aminoesters were released from the polymer support by transesterification employing methanol in the presence of triethylamine. 

Another metal-catalyzed microwave-assisted transformation performed on a polymer support involves the asymmetric allylic malonate alkylation reaction shown in Scheme 12.4. The rapid molybdenum(0)-catalyzed process involving thermostable chiral ligands proceeded with 99% ee on a solid support. When TentaGel was used as as support, however, the yields after cleavage were low (8-34%) compared with the corresponding solution phase microwave-assisted process (monomode cavity) which generally proceeded in high yields (>85%) [30],... 

In contrast with the reactions involving sulphide or hydrogen sulphide anions, aryl alkyl thioethers and unsymmetrical dialkyl thioethers (Table 4.3) are obtained conveniently by the analogous nucleophilic substitution reactions between haloalkanes and aryl or alkylthiols under mildly basic conditions in the presence of a quaternary ammonium salt [9-15] or polymer-supported quaternary ammonium salt [16]. Dimethyl carbonate is a very effective agent in the formation of methyl thioethers (4.1.4.B) [17]. 

The base-catalysed addition of thiols to Jt-electron-deficient alkenes is an important aspect of synthetic organic chemistry. Particular use of Triton-B, in place of inorganic bases, has been made in the reaction of both aryl and alkyl thiols with 1-acyloxy-l-cyanoethene, which behaves as a formyl anion equivalent in the reaction [1], Tetra-n-butylammonium and benzyltriethylammonium fluoride also catalyse the Michael-type addition of thiols to a,P-unsaturated carbonyl compounds [2], The reaction is usually conducted under homogeneous conditions in telrahydrofuran, 1,2-dimethoxyethane, acetone, or acetonitrile, to produce the thioethers in almost quantitative yields (Table 4.22). Use has also been made of polymer-supported qua-... 

In a manner analogous to that used for the formation of 5-alkyl thioacetates using a polymer-supported quaternary ammonium salt (4.1.31), the dithiocarbamate anion can be 5-alkylated under mild conditions [3]. The corresponding arylation reaction with activated aryl systems requires more vigorous conditions ... 

Alkyl and glycosyl isocyanates and isothiocyanates are produced in good yield under phase-transfer catalytic conditions using either conventional soluble catalysts or polymer-supported catalysts [32, 33]. Acyl isothiocyanates are obtained under similar conditions [34]. A-Aryl phosphoramidates are converted via their reaction with carbon disulphide under basic conditions into the corresponding aryl isothiocyanates, when the reaction is catalysed by tetra-n-butylammonium bromide [35]. 

In the main, the original extractive alkylation procedures of the late 1960s, which used stoichiometric amounts of the quaternary ammonium salt, have now been superseded by solid-liquid phase-transfer catalytic processes [e.g. 9-13]. Combined soliddiquid phase-transfer catalysis and microwave irradiation [e.g. 14-17], or ultrasound [13], reduces reaction times while retaining the high yields. Polymer-supported catalysts have also been used [e.g. 18] and it has been noted that not only are such reactions slower but the order in which the reagents are added is important in order to promote diffusion into the polymer. 

The reductive dehalogenation of haloalkanes has also been achieved in high yield using polymer supported hydridoiron tetracarbonyl anion (Table 11.15). In reactions where the structure of the alkyl group is such that anionic cleavage is not favoured, carbonylation of the intermediate alkyl(hydrido)iron complex produces an aldehyde (see Chapter 8) [3]. 

Chiral benzamides I and the pyrrolobenzodiazepine-5,11-dio-nes n have proven to be effective substrates for asymmetric organic synthesis. Although the scale of reaction in our studies has rarely exceeded the 50 to 60 g range, there is no reason to believe that considerably larger-scale synthesis will be impractical. Applications of the method to more complex aromatic substrates and to the potentially important domain of polymer supported synthesis are currently under study. We also are developing complementary processes that do not depend on a removable chiral auxiliary but rather utilize stereogenic centers from the chiral pool as integral stereodirectors within the substrate for Birch reduction-alkylation. 

Various transition metal catalysts, including those based on Rh, Pt, Pd, Co, and Ti, have been bound to polymer supports—mainly through the phosphenation reaction described by Eq. 9-65 for polystyrene but also including other polymers, such as silica and cellulose, and also through other reactions (e.g., alkylation of titanocene by chloromethylated polystyrene). Transition-metal polymer catalysts have been studied in hydrogenation, hydroformylation, and hydrosilation reactions [Chauvin et al., 1977 Mathur et al., 1980]. 

Undesirable intermolecular reactions can be avoided during certain synthetic conversions. Thus it is often useful to carry out C-alkylation and C-acylation of compounds that form enolate anions, for example, esters with a-hydrogens. Such reactions are often complicated by self-condensation since the enolate anion can attack the carbonyl group of a second ester molecule. Attachment of the enolizable ester to a polymer support at low loading levels allows the alkylation and acylation reactions (Eq. 9-79) to be performed under... 

Beside borosilicate and fused silica capillaries, PS/DVB monoliths have been fabricated within the confines of steel and PEEK tubings [52]. In order to increase the hydrophobic character of the supports, a Friedel-Crafts alkylation reaction was used for the attachment of Cig-moieties to the polymer surface. The derivatized material was demonstrated to be more retentive and to provide more efficient peptide separations compared with the original, nonderivatized monolith. 

When the reactions of alkyl bromides (n-Q-Cg) with phenoxide were carried out in the presence of cosolvent catalyst 51 (n = 1 or 2,17 % RS) under triphase conditions without stirring, rates increased with decreased chain length of the alkyl halide 82). The substrate selectivity between 1-bromobutane and 1-bromooctane approached 60-fold. Lesser selectivity was observed for polymer-supported HMPA analogue 44 (5-fold), whereas the selectivity was only 1,4-fold for polymer-supported phosphonium ion catalyst 1. This large substrate selectivity was suggested to arise from differences in the effective concentration of the substrates at the active sites. In practice, absorption data showed that polymer-supported polyethylene glycol) 51 and HMPA analogues 44 absorbed 1-bromobutane in preference to 1-bromooctane (6-7 % excess), while polymer-supported phosphonium ion catalyst 1 absorbed both bromides to nearly the same extent. 

Xu, W. Mohan, R. Morrissey, M. M. Polymer Supported Bases in Solution-Phase Synthesis. 2. A Convenient Method for /V-Alkylation Reactions of Weakly Acidic Heterocycles, Bioorg. Med. Chem. Lett. 1998, 8, 1089. 

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