Wang resin-bound urea

These core structures can be accessed as shown in Scheme 19. Michael addition of primary amines to Wang resin-bound acrylic acid 66 produced 3-aminoesters 67, which were reacted with isocyanates to give precursor ureas 68 for cyclization. Treatment of 68 with TFA/water (19 1) at room temperature cleaved mainly the non-cyclized precursors, whereas cyclized products 69 were formed by treatment under rather harsh conditions (toluene saturated with HCl, sealed vial, 95 °C) and were isolated in yields in the range 13-76% [32]. 

Dewitt et al. [58,59] also reported the synthesis of 40 hydantoins 20 using the Diversomer approach following the condensation of a variety of isocyanates to Wang resin-bound amino acids. Concomitant cyclization and cleavage leading to the hydantoin product occurred on heating the resin-bound urea in 6 M HCl (Fig. 11). 

A novel solid-phase version of the Biginelli three-component condensation has been recently disclosed [359]. Since the reaction proceeds via formation of an N-acyliminium ion intermediate from the aldehyde and the urea precursors, these components were first combined and then reacted with the resin-bound fi-ketoe-ster (454). Highly loaded (2.53 mmol g ) fi-ketoester Wang resin was utilized in order to increase the amount of final product (Scheme 94). Using this strategy, eleven different dihydropyrimidones (458) have been prepared. 

In a similar approach, Kim et coupled N-Fmoc protected amino acids 275 to the Wang resin 84 under standard conditions and, after deprotection, reductively alkylated the free amino group using different aldehydes and NaBHjCN to give polymer-bound amines 277. Reaction with different isocyanates provided immobilised ureas 278. Upon treatment with neat diisopropylamine, hydantoin derivatives 274 were rapidly formed with simultaneous cleavage from the resin in high yields and purities Scheme 4.4.7). 

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