Postcondensation modifications of Ugi four-component condensation products: 1-Isocyanocyclohexene as a convertible isocyanide. Mechanism of conversion, synthesis of diverse structures, and demonstration of resin capture

Article abstract of DOI:10.1021/ja953868b

The concept of a 'universal isocyanide' that enables postcondensation modification of Ugi four-component condensation products is introduced. This strategy is suited for the synthesis of libraries. By using 1-isocyanocyclohexene as the isocyanide input in the Ugi reaction, the product cyclohexenamides can be converted to a variety of products. From the original α-(acylamino) amides, new carboxylic acids, esters, and thioesters are produced from acid-activated conversion of the cyclohexenamide moiety. It has been determined that the intermediate in conversion of this type is an oxazolinium-5-one (munchnone) that reacts with many nucleophiles to yield the products above. The munchnone can also undergo cycloaddition with acetylenic dipolarophiles to form pyrroles. Through internal nucleophilic attack, Ugi products are shown to convert to a protected monosaccharide derivative and to 1,4-benzodiazepine-2,5-diones. All of the conversions described consist of a single step. Resin capture of Ugi products is demonstrated, in which a solution condensation reaction is followed by trapping of the products onto solid support resin. Both the trapping step and subsequent cleavage of products from the resin occur in very high yield.