4-DMAP polymer-supported

Polymer-bound 1-hydroxybenzotriazole 1008 reacts with carboxylic acids in the presence of 1,3-diisopropylcarbo-diimide (1,3-DIC) and DMAP to produce esters 1009. Treated with hydroxylamine, esters 1009 are converted to hydroxamic acids 1010 (Scheme 167) <20030BC850>. Starting 1-hydroxybenzotriazole 1008 is recycled in the process and can be used for other syntheses. This method is well suited for automated synthesis of a library of hydroxamic acids. In similar applications of polymer-supported 1-hydroxybenzotriazole 1008, a wide variety of amides is synthesized <1997JOC2594, 2002JC0576>. 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

Insoluble polymer-supported catalysts ion exchange resins, poly-DMAP, poly-vinyl pyridine, and others... 

RCO2H, R OH, DCC/DMAP, EtjO, 25°C, l-24h, 70-95% yield. This method is suitable for a large variety of hindered and unhindered acids and alcohols. The use of Sc(OTf)3 as a cocatalyst improves the esterification of 3° alcohols. Carboxylic acids that can form ketenes with DCC react preferentially with aliphatic alcohols in the presence of phenols whereas those that do not show the opposite selectivity. In some sterically congested situations the 0-acyl urea will migrate to an unreactive A-acyl urea in competition with esterification. Carbodi-imide I was developed to make the urea by-product water soluble and thus easily washed out. Isoureas are prepared from a carbodiimide and an alcohol which upon reaction with a carboxylic acid give esters in excellent yield. A polymer supported version of this process has been developed. This process has been reviewed. Note that DCC is a potent skin irritant in some individuals. 

Polymer-supported sulfonyl chlorides can be used for the selective monosulfonyl-ation of anilines, as demonstrated by the Ley group [71, 72], Commercially available polystyrene-DMAP (4-dimethylaminopyridine) was treated with different aryl sulfonyl chlorides to form polymer-bound sulfonylation reagents. These were reacted with substituted anilines to form an array of hydroxamic acids (Scheme 6.17), using a synthetic strategy involving polymer-bound reagents in all steps. The products were subsequently evaluated as histone deacetylase inhibitors. 

The resin-supported carbodiimide 2 (R = Cy), related to the popular solution phase reagent dicyclohexylcarbodiimide (DCC), has been the most successfully employed polymeric carbodiimide of this series, especially in the presence of additives to accelerate the coupling reaction and avoid the acylisourea-unreactive acylurea rearrangement [2]. This carbodiimide has been used for esterification reactions, as exemplified in the reaction of dithiane-containing alcohol 3 with Fmoc-protected valine in the presence of a catalytic amount of N,N-dimethylami-nopyridine (DMAP) to give ester 4 [10] (Scheme 7.1). This polymer-supported reagent 2 (R = Cy) has also been used without any additive in the amidation reaction of 3,4-diaminocyclopentanol scaffolds with 2-(methylsulfanyl)acehc acid [11]. 

Polymer-supported equivalents of the widely used organic base 4-(dimethylamino)pyridine (DMAP) were soon developed, but many of their reported applications are as a stoichiometric base. Resin 37 (Scheme 10.10), containing a polyethylene imine) matrix was the first supported system to be prepared. Those materials were more efficient catalysts than DMAP itself, under the same conditions, for the hydrolysis of p-riilropheriyl esters in aqueous solution [175, 176],... 

For synthetic applications, DMAP analogues supported on PS-DVB resins have been the most widely used. Polymer 39 was prepared from a 4% cross-linked... 

Selective protection of dihydropyrimidinones has been used in a novel approach to improve the synthesis of valuable Biginelli compounds with different substitution patterns [130]. This procedure has been successfully catalyzed by polymer-supported NjN-dimethylaminopyridine (PS-DMAP) (Scheme 16.85). This micro-... 

The microwave-assisted one-pot three-step synthesis of thiohydantoins has been studied together with a polymer-supported catalyst and/or reagent [55]. Cyclization of a number of AT-substituted amino acids of type 50 and thioiso-cyanates 51 has given satisfactory yields within 5 min at 170 to 180 °C (see Scheme 29). Polymer-supported dimethylaminopyridine (PS-DMAP) 52 has been utilized as a supported base herein to catalyse the reaction however, in most cases the yield was comparatively lower to the use of triethylamine (TEA). PS-DMAP also assisted in simplifying the purification. 

Using these methods we more recently reported the synthesis of another isoquinoline alkaloid, (-)-norarmepavine (Scheme IS.IO). " This was accomplished by coupling the amine 26 with the ester 27 to give an intermediate amide (28). This was best done using focused microwave irradiation under solvent-free conditions. Next, 28 was converted to a Bischler-Napieralski product by using a combination of triflic anhydride and PS-DMAP. This was followed by scavenging with polymer-supported A(-(2-aminoelhyl)aminomethyl polystyrene to remove any excess anhydride. The intermediate triflate was then converted to the free base 29 with PS-BEMP (7), mentioned earlier. Finally, a proline-derived reductant... 

DMAP = N,N-dimethylaminopyiidine, DMF = N -dimethylformamide, DCM = dichloromethane, PTAT = phenyltrimethylammonium tribromide, EO = ethylene oxide, PO = propylene oxide, ECH = epichlrohydrin, SO = styreneoxide, AGH = allylicglycidil ether. BO = butylene oxide, HO = n-hexene oxide, DO = N-decene oxide, PPO = 2-phenylpropylene oxide, PS-DFILX = polymer supported diol functionalized ionic liquids, acac = acetyl acetonate, CIL= carboxylic-acid functionalized imidazolium-based ILs, note active site consideration for TOP calculation is not uniform. Co-valent triazine complexes... 

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