Rink-isonitrile resin

Gilley CB, Kobayashi Y (2008) 2-nitrophenyl isocyanide as a versatile convertible isocyanide rapid access to a fused y-lactam (3-lactone bicycle. J Org Chem 73 4198 204 Chen JJ, Golebiowski A, Klopfenstein SR, West L (2002) The universal Rink-isonitrile resin applications in Ugi reactions. Tetrahedron Lett 43 4083 085 Hulme C, Peng J, Morton G, Salvino JM, Herpin T, Labaudiniere R (1998) Novel safety-catch linker and its application with a Ugi/De-BOC/Cyclization (UDC) strategy to access carboxylic acids, 1, 4-benzodiazepines, diketopiperazines, ketopiperazines and dihydroqui-noxalinones. Tetrahedron Lett 39 7227-7230... 

Diketopiperazines and benzodiazepin-2,5-diones represent the same target obtained by performing a Ugi MCR on the universal Rink-isonitrile resin [347]. The final product could be cleaved from the resin with HOAc/1,2 dichloroethane 1 9 (v/v). Wang resin-bound isonitrile (419) has been employed in a Ugi MCR-N-acyli-minium ion cyclization [348]. Using aminoacetaldehyde diethyl acetal (420) and then exposing the Ugi products to a 20% dichloromethane solution of TFA, the desired A -2-oxopiperazines (422) were obtained with simultaneous release from the resin (Scheme 86). 

Universal Rink-isonitrile resin (450) has been applied to the synthesis of imi-dazo[l,2-a]pyridines (452) [356], a novel [357] MCR consisting of a condensation among 2-aminopyridines, aldehydes, and isonitriles. During the course of the reaction, the isonitrile component becomes an enamine. The reaction was performed in the presence of a catalytic amount of para-toluenesulfonic add in a desiccating mixture of CHCU/MeOH/trimethylorthoformate (TMOF) (Scheme 92). 

TsOH (0.32 g, 1.8 mmol) were mixed in CHCls/MeOH/TMOF 1 1 1 (v/v/v) for 2 h. The mixture was then added to the Rink-isonitrile resin (2.0 g, 1.8 mmol). The suspension was agitated overnight at ambient temperature. The resin was washed with N,N-dimethylformamide (DMF), MeOH, 10% DIPEA/CH2CI2, CH2CI2, MeOH, and then dried to afford the intermediate resin. 

Good yields and purities were obtained for the two examples shown. Ugi reaction using solid-supported benzenesulfonamide, prepared by coupHng 4-carbox-ybenzenesulfonamide onto Rink resin, has also been described. The sulfonamide took the place of the amino component in the classical Ugi MCR. An extension of this Ugi reaction involving a support-bound amine, furfural, and an isonitrile and an acrylic acid was used by Schreiber [307] to generate support-bound dipeptides capable of performing intramolecular Diels-Alder reactions (see Section 4.5.9). 

Very recently, a polymer-supported construct for quantifying the reactivity of monomers involving multicomponent Ugi strategies was reported [53]. The authors investigated the Ugi four-component condensation of a set of aldehydes, acids, and isonitriles. The amine compound used was bound to a specially modified Rink amide polystyrene resin bearing an ionization leveler and bromine functionality as a mass splitter for accurate analysis by positive electrospray ionization mass spectrometry. The microwave-assisted experiment was performed with a set of ten carboxylic acids, hydrocinnamaldehyde, and cyclohexyl isonitrile in DCM-... 

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