Hydroxamic acids polymer-bound

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>. 

The rate-enhancing effect of cationic detergents was analyzed by using Hill s equation. The observed exponent (n = 3 — 4) suggests that polymer-bound detergents facilitate the subsequent binding acceleratively hence the sigmoidshaped dissociation behavior of hydroxamic acid. 

K. 0-Linked Polymer-bound A-Substituted Hydroxamic Acids. 214... 

In 2003, Devocelle and colleagues reported a convenient two-step procedure for the parallel synthesis of hydroxamic acids (or O-protected hydroxamic acids 207) from carboxylic acids and hydroxylamine. It involves the formation of a polymer-bound HOBt active ester 206 from 204 and the acid 205 and subsequent reaction with O-protected or free hydroxylamine (Scheme 89). The use of free hydroxylamine leads to increased yields while maintaining high purities. Recycling of the exhausted resin 204 to prodnce the same or a different hydroxamic acid has been achieved by a three-step protocol, which is easily amenable to automation and cost-economical. 

O-linked polymer-bound Af-substituted hydroxylamines are prepared by reduction of resin-bound oximes with borane-pyridine complex in the presence of dichloroacetic acid (Scheme 94). Other reducing systems commonly used for imine or oxime reduction are ineffective, including borane-pyridine in the presence of acetic acid. Subsequently, the A-substituted products are acylated and cleaved from the resin to afford Af-substituted hydroxamic acids 220. ... 

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 majority of reported solid-phase combinatorial syntheses of the lactam core utilize a [2-i-2] cycloaddition reaction of ketenes with resin-bound imines [33-41]. A further development of the Staudinger reaction was reported by Mata and coworkers using Mukaiyama s reagent [42]. In addition, a stereoselective synthesis of chi-rally pure P-lactams has been performed as a first utilization of polymer-supported oxazolidine aldehydes [43]. Other strategies include an ester enolate-imine condensation [44], an Hg(OCOCF3)2-mediated intramolecular cydization [45], and Miller hydroxamate synthesis [46]. Because of the variability derived from the scaffold synthesis, not many attempts have been made to derivatize the resin-bound lactam template [47]. One of the most detailed descriptions of a versatile (3-lactam synthesis on a resin employed amino acids tethered as esters on Sasrin resin [48]. 

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