Catch-and-release

High-speed synthesis of thiadiazoles has been recently completed on a solid support system using a catch and release technology to provide novel thiadiazoles. The solid-supported sulfonylhydrazine reacts with ketones to provide the solid phase hydrazones (catch) and formation of the thiadiazole with subsequent release of the... 

Catch and Release Synthehc Route to 2,4,5-trisubstituted Pyrimidines. . 98... 

A very interesting catch and release methodology has been developed by Porcheddu for the preparation of several interesting heterocycles [76,77]. The... 

Scheme 13 Divergent catch-and-release synthesis of heterocycles...

Fig. 2 Various polymer-supported bases used in the catch-and-release synthesis of pyra-zoles, isoxazoles and 2-aminopyrimidines...

A catch and release synthesis of tetrazoles and cyclic amidines has been reported making use of solid-supported oximes [94]. When bound sulpho-nyloximes, obtained by reacting polymer supported sulfonyl chloride with oximes, were reacted with nucleophiles, tetrazoles or cychc amidines were obtained (Scheme 19). Alternatively, the use of TMS-CN affords imino nitriles, which have been used as intermediates for the preparation of indoles, 1,2,3,4-tetrahydropyridines, quinoxalines and benzimidazoles. 

Canthine skeleton 52 Cardiotonic agent, heart failiu-e 3 Caspase-3 inhibitors, non-peptide 269 Catch and release , 2,4,5-trisubstituted pyrimidines 98 Chloro dehydroxylation 17 Click chemistry, 1,4-disubstituted triazoles 45... 

Figure 16.5 A catch-and-release ICAT design incorporates a gem-methyl group and an isopropyl group on either side of a disulfide bond within its spacer arm. The hindered disulfide permits the use of standard reducing gel electrophoresis conditions using DTT without reduction. After purification on a (strept)avidin affinity column, however, the disulfide group can be cleaved with TCEP, which provides recovery of the labeled peptides prior to mass spec separation.

Gartner, C.A., Elias, J.E., Bakalarski, C.E., and Gygi, S.P. (2007) Catch-and-release reagents for broads-cale quantitative proteomics analyses./. Broteome Res. 6(4), 1482-1491. 

A parallel synthesis of 1,2,3-thiadiazoles employing a catch-and-release strategy has been reported using the Hurd-Mori reaction. A polymer-bound tosyl hydrazide resin reacted with a-methylene ketones to afford a range of sulfonyl hydrazones. Treatment of these sulfonyl hydrazones with thionyl chloride causes 1,2,3-thiadiazole formation and cleavage of the resin in one step <1999JOC1049>. 

Baxendale IR, Ley SV, Smith CD, Tranmer GK (2006d) A flow reactor process for the synthesis of peptides utilizing immobilized reagents, scavengers and catch and release protocols. J Chem Soc Chem Commun 4835-4837... 

Figure 3.17 Amine catch and release purification with a silica-supported acid.

Unfortunately, many reactions do not occur with quantitative conversion and in near absolute purity. The work-up and purification of most chemical processes probably takes up most of a bench chemists time. Therefore techniques that simplify and accelerate these operations not only free up valuable time, but allow greater creativity and increased levels of output. Here again, supported systems can be used to aid the chemist in the guise of scavengers, quenching agents and catch and release systems. 

Scheme 2.12 Catch and release purification of carbonyl compounds.

Scheme 2.13 Systematic reaction/ catch and release purification. 

A number of polymer assisted procedures have been described that have subsequently become standard practice within the domain of solution-phase hbrary synthesis (complementary molecular reaction and recognition, scavenging, tagged reagent systems and catch and release protocols). A number of these concepts have... 

Scheme 2.49 A modified catch and release protocol for the synthesis of 1,2,3-thiadia-zoles.

An alternative strategy towards benzimidazole synthesis relies on the palladium-catalysed cyclisation of (2-bromophenyl)amidines. This chemistry has been reported to take place under aqueous reaction conditions, in the presence of sodium hydroxide in sealed microwave vials. The products were isolated by a catch and release method using a strongly acidic ion exchange resin, thereby avoiding conventional chromatographic purification (Scheme 3.14)23. Selectively, N-functionalised benzimidazoles were conveniently prepared by this method. 

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. 

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