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

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 (münchnone) that
reacts with many nucleophiles to yield the products
above. The münchnone 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.