Studies on the Chemistry and Reactivity of α-Substituted Ketones in Isonitrile-Based Multicomponent Reactions†

Using the Passerini and Ugi reactions as representative tests, the utility of several α-substituted ketones R−CO−CH2−X (X = sulfonyloxy, acyloxy, azido, halo, hydroxy, and sulfonyl) in isonitrile-based multicomponent reactions was explored. In a relative rate study (R = PhCH2CH2), each of the α-substituted ketones underwent Passerini condensation more rapidly than the parent ketone. Short, highly convergent routes to oxazoline, β-lactam, di-O-acylglyceramides, and other molecular frameworks were developed.