TentaGel-support

Furthermore, cyanation followed by a subsequent cycloaddition, forming a tetrazole, was implemented as a rapid one-pot procedure on TentaGel-support, as depicted in Scheme 18. Only an insignificant decay of the solid support was experienced under the high-temperature conditions applied. 

Wennemers found that tripeptide H-Pro-Pro-Asp-NH2 was a highly active and selective catalyst for asymmetric aldol reactions [44]. This peptide was immobihzed to a polymer support and used as a catalyst for the aldol reaction of p-nitrobenzal-dehyde 73 and acetone (Scheme 3.21). By using a TentaGel-supported peptide 73 the aldol adduct 69 was obtained in 89% yield with 75% ee, while a polyethylene glycol-polyacrylamide (PEGA)-supported peptide gave the same adduct in 93% yield and 79% ee [45]. 

Figure 15 Glycosylation using control pore glass, polystyrene, and Tentagel supports.

The microwave acceleration of Ugi condensations on a sohd support have been utilized in the synthesis of an 18-membered targeted hbrary of a-acylamino amides [60], Irradiation of the four components, immobilizing the amine on TentaGel S RAM, for 3-5 min in a single-mode microwave synthesizer gave the products in moderate to excellent yields and high purity (Scheme 7). 

The first example of microwave-promoted solid-phase methodology in heterocyclic chemistry was the arylation of thiophene and indole via Suzuki couplings on TentaGel S RAM resin, as demonstrated by Hallberg and coworkers in 1996, before temperature- and pressure-controlled microwave instruments were even available [189]. Three years later Schotten and coworkers presented analogous but aqueous Suzuki couplings of 5-bromo-thiophene anchored to PEG soluble support via a carboxylic function at its C-2 position [116]. Unfortunately, this work was performed in a do-... 

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... 

The first solid-phase application of the Ugi four-component condensation, generating an 18-member acylamino amide library, was presented in 1999 by Nielsen and Hoel [53]. The authors described a library generation utilizing amino-functionalized PEG-polystyrene (Tentagel S RAM) as the solid support (Scheme 7.36). A set of three aldehydes, three carboxylic acids, and two isonitriles was used for the generation of the 18-member library. 

The same authors performed a microwave assisted Stille reaction on the Rink amide (RAM) Tentagel polymer-tethered 4-iodobenzoic acid [5 b]. Successful palladium-catalyzed coupling of heteroaryl boronic acid with anchored 4-iodobenzoic acid enabled both >99% conversion of the starting material within 3.8 min (45 W) and a minimal decomposition of the solid support. The coupling reactions were realized in a mixture of polar solvents (H20-EtOH-DME, 2.5 1.5 6). 

Interestingly, the Suzuki reaction worked smoothly on solid supports and high yields of a variety of products were reported under these reaction conditions (Eq. 11.22) [36]. 4-Bromo- and 4-iodobenzoic acid linked to Rink-amide TentaGel re-... 

The coupling and cycloaddition could also be achieved as a one-pot procedure on a polymer support, as shown in Eq. (11.34), in which a Rink linker on TentaGel was used. Negligible decomposition of the solid support was reported [50]. 

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],... 

Table 9.1 shows the method s versatility across several solid-support types. Care must be taken to dry the tentagel resins by lyophilization for 24 h before subjecting them to the reaction conditions. In the examples shown, quantitative conversions were obtained as determined by elemental analysis and 13C NMR. The mild reaction conditions are most evident by the quantitative conversion of SASRIN resin to its corresponding chloromethyl... 

PEG has been converted into a solid support by grafting functionalized polyethylene glycol chains onto polystyrene to form constructs such as TentaGel ... 

Despite the success with gel-phase NMR spectroscopy the spectra obtained are of limited value because of the broad peaks, and indeed the NMR spectra of unlabelled samples need relatively long acquisition times (because of the low abundance of C) especially with lightly loaded resins such as TentaGel and Argo-Gel. NMR [206, 207] and NMR [208, 209] spectroscopy of gel beads have also been shown to be a convenient NMR technique for monitoring reactions of fluorine or phosphorous-containing molecules, respectively, attached to solvent-swollen polymer supports. 

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