Supported Amine

Palladium-catalyzed organic synthesis has been utilized throughout the pharmaceutical industry, taking advantage of its C-C bond formation capability. However, the issue of residual levels of palladium has been a major concern due to its ability to attenuate biological screens. To address this, several scavengers 

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Polymer-NH(CH2),NH2, (jc = 2, 4, 6), BuOH, 85°, 92-96% yield. The polymer-supported amine helps in the final purification of oligosacchar-rides that have used the TCP group for —NH2 protection. ... 

The Pictet-Spengler reaction has been carried out on various solid support materials " and with microwave irradiation activation.Diverse structural analogues of (-)-Saframycin A have been prepared by carrying out the Pictet-Spengler isoquinoline synthesis on substrates attached to a polystyrene support. Amine 20 was condensed with aldehyde 21 followed by cyclization to give predominantly the cis isomer tetrahydroisoquinoline 22 which was further elaborated to (-)-Saframycin A analogues. 

In place of N-methylimidazole (Melm), only dimethylaminopyridine (DMAP) could be substituted. The solid-supported amines piperidinomethyl- or morpholinomethyl polystyrene resins, pyridine, and tertiary amines like triethylamine andN-methylmorpholine were not effective. 

As for the solid support, several polymer-supported amines were tested (Fig. 2). For either the pyrazole and isoxazole synthesis, the best results were given by aniline-functionalized cellulose, which has also the advantage of a relatively low cost. For the 2-aminopyrimidine library, polystyrene-based piperazine and piperidine gave products with a much higher purity compared with other secondary non-cyclic or primary amines, hi both cases, the resins could be reused for up to four times before degradation in their behavior was observed. This reusability could be further enhanced (up to 10 cycles for cellulose-based aniline) when the microwave-assisted protocols were used. 

Kobayashi S, Aoki Y. />-Benzyloxybenzylamine (BOBA) resin. A new polymer-supported amine used in solid-phase organic synthesis. Tetrahedron Lett 1998 39 7345-7348. 

A number of amines have been investigated for their suitability as polymerisation initiators, including aliphatic amines (such as butylamine [17] and 1,3-diaminopropane [18]), polymer supported amines (such as cross-linked aminomethyl polystyrene [CLAMPS], Fig. 1, giving rise to immobilised polyamino acids [19]) and resin-bound amines. 

Polymer-supported amine oxides 47-49 were catalytically active for the reaction of 1-bromooctane with aqueous sodium cyanide, 66). 

The catalysts were conditioned in a 1-cyanooctane/aqueous NaCN mixture for 24 h at room temperature to avoid the induction period of the reaction. Rates (converted from a weight basis to a molar basis) with catalysts 47-49 significantly decreased as the % RS increased over the range 5 % to 50 %. With equal loadings activities of the polymer-supported amine oxides decreased with decreased lipophilicity of the catalysts (49 > 48 > 47). Lipophilic character appears to be an important factor for activity of polymer-supported cosolvents. 

Both the rhodium and the cobalt complexes catalyze olefin isomerization as well as olefin hydroformylation. In the case of the rhodium(I) catalysts, the amount of isomerization decreases as the ligands are altered in the order CO > NR3 > S > PR3. When homogeneous and supported amine-rhodium complexes were compared, it was found that they both gave similar amounts of isomerization, whereas with the tertiary phosphine complexes the supported catalysts gave rather less olefin isomerization than their homogeneous counterparts (44, 45). 

Four supported amines, one primary, one secondary, and two arylamines, were reacted with guanylating agents in solution and on a solid phase in a set of comparative experiments (Scheme 19).41 The supported primary and secondary amines 15 and 16 gave high yields of product (>85%) when... 

Base catalysis is one of the less-well developed areas of heterogeneous catalysis. We have developed novel bases derived from amines via the one-step process outlined above. A range of supported amines have been prepared and evaluated in a series of reactions We have also investigated the nature of the amine groups attached to the surface in comparison with those formed by grafting onto pre-formed silica. While many workers have studied the use of basic catalysts for the Knoevenagel condensation of aldehydes, with three articles on the use of MCM derivatives[ 12], little has been done on the more demanding condensation of ketones. 

Although various chiral glycosyl aldehydes with a direct attachment of the carbonyl group to the anomeric center showed low diastereoselectivity [52], a moderate stereoselectivity was observed in the condensation of 45 with methyl isocyanoa-cetate, propionic acid and a solid-supported amine [53]. 

Finn [66] has reported that when alkenyl boronic acids are used in this process, the aminomethylphenol intermediates can undergo a further transformation to generate 2Ff-chromenes 153 (Scheme 7.20). This process can be done efficiently with catalytic amounts of dibenzylamine or the corresponding polymer-supported amine 154 to afford a variety of substituted 2H-chromenes 155-159 in one step. 

Tanthana J, Chuang SSC (2010) In situ infrared study of the role of PEG in stabilizing silica-supported amines for C02 capture. ChemSusChem 3(8) 957-964... 

Alkyl iodides may be transformed into aldehydes by reaction with polymer-supported amine oxide reagents359. This type of reagent dramatically reduces side-reactions, compared to other traditional oxidations in solutions and usually occurs much faster and in higher yields. Oxidation with 4-dimethylaminopyridine N-oxide has also given excellent yields of aldehydes, starting from both chlorides and bromides360. 

Different applications of these functional materials can be designed like their use as scavenger -in particular for supported amine and acids- and as supported catalysts. An example of such a last application could be found in the reduction of alkyl halides by triethylsilane. 

The amorphous silica-supported amine systems show promising selectivity and recyclability for the heterogeneous catalysis of the Knoevenagel reaction (scheme 1). However they also demonstrate distinct limitations on the choice of solvent for the reaction and moderate turnover numbers.3 Materials prepared via grafting of HMS or in-situ preparation of organo-functionalised HMS will hopefully overcome these limitations. 

The halide linkers 1.8 (64), which can be prepared from Wang resin, have been used to support amines and to release sulfonamides using 95% TFA-DCM (R = H) or 5% TFA-DCM (R = OMe). 

The indole linker 1.11 (68), easily prepared from aminomethyl PS resin and N-carboxyalkylated indole-3-carboxaldehyde, was used to support amines and to transform them on SP, obtaining, by release with TFA-DCM 1/1 in 30 min, a variety of compounds, including amides, sulfonamides, guanidines, ureas, and carbamates. 

The acetyldimedone linker 1.16 (73) is another example of a linker attached to an aminomethyl PS resin and has been used to support amines and amino acids during SPS. The products are released containing free amino groups. The cleavage conditions are typically 2% hydrazine-DMF for 5 min at rt. 

Oxaziridine 313 was prepared by Ley and co-workers using solid-supported reagents and scavengers <2002T6285>. Reaction of imine 312 with MCPBA followed by treatment with a solid-supported amine afforded the oxaziridine in 95% yield. 

Since silica is such a common support for immobilization, the effect of the weakly acidic silanol groups has been studied. A cooperative silanol effect is thought to improve the catalytic activity of mesoporous silica-supported amines in base-catalyzed reactions such as the nitroaldol (Henry) condensation [6, 7], Knoevenagel condensation [6, 8,9], and Michael addition [6]. Thus immobilizing amines onto supports with stronger acid groups could be expected to further increase the catalytic activity. 

Nucleophilic reactions of unmodified aldehydes are usually diiScult to control, affording complex mixture of products, often due to the high reactivity of the formyl group under either basic or acidic reaction conditions. The activity order of the supported amines was secondary > primary > tertiary, which may suggest the intervention of an enamine pathway the enals were exclusively obtained as ( ) isomers. Notably, FSM-16-(CH2)3-NHMe exhibited higher activity than conventional solid bases such as MgO and Mg-Al-hydrotalcite [hexanal self-aldol condensation FSM-16-(CH2)3-NHMe 97% conversion and 85% yield in 2h, MgO 56% conversion and 26% yield in 20 h, Mg-Al-hydrotalcite 22% conversion and 11% yield in 24 h]. 

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