Resin-Bound CICs

SCHEME 7.91 Mechanism of hydrolysis of the l-hydroxy-2-methyl-2-propyl isocyanide group. 

2 Resin Bound CyEIC Piscopio, at Amgen, reported a synthesis of odorless resin-bound CIC Izh based on Armstrong s CIC [108]. It can be prepared from 4-(4-hydroxyphenyl)-cyclohexanone using Merrifield as a base resin. Loading in the 0.7-0.8 mmol/g range was achieved and reactions can be monitored by on-bead Fourier transform infrared spectroscopy. Hulme and coworkers have employed the resin-bound CIC Izh in the so-called UDC (Ugi/De-Boc/Cyclization) strategy to synthesize bicyclic y-lactam 304 [109]. The U-4CR of resin-bound CIC Izi, y-keto acid lOza and amine 6zg affords resin-bound y-lactam 304. Acetyl chloride 

SCHEME 7.94 Synthesis of bicyclic y-lactam 305 using resin bound CIC Izh. 

3 Universal Rink Resin CIC Chen and coworkers utilized Hofheinz-Isenring s CIC concept and developed universal rink resin isocyanide Izi [110]. 

Chen and coworkers have utilized resin-bound CIC Izi in the U-4CR [108,111 ] to synthesize a wide variety of biologically relevant heterocyclic scaffolds, for example, 3-acylamino imidazo[l,2-a]pyridines 308, DKPs 310, BDZs 312 and 5-substituted 

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Universal Resin-Bound Carbonate CIC Kennedy and coworkers developed a novel, universal resin-bound carbonate CIC Izj on the basis of Lindhorst and Ugi s CIC Ip [112], Resin-bound chloroformate 315 can be generated by treating hydroxymethyl polystyrene twice with a 20% phosgene/toluene solution and washing extensively. The lithium alkoxide lo can be prepared by the treatment of -butyl lithium with 4,4-dimethyl-2-oxazoline (135) in anhydrous THF at -78°C under a steady flow of argon and transferred via cannula to the solution of 315 in anhydrous THF at 0°C to afford Izj (Scheme 7.97). The resin is stable at room temperature and can be reproduced on a 200-g scale with a loading level of 0.87 mmol/g [112]. 

The resin-bound carbonate CIC Izj has been found to perform well with a variety of amines, aldehydes, and acids in the U-4CR to provide acyclic Ugi products 316 and... 

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