A simple approach to complexity: The reactivity pattern of α‐isocyanoacetates can be tuned by modulating the acidity of the α CH bond(s) against the nucleophilicity of the conjugate base. The unique reactivity of the α‐(p‐nitrophenyl)‐α‐isocyanoacetate 1 was exploited in a three‐component synthesis of 5‐methoxyoxazoles 2 and four‐component synthesis of furopyrrolones 3. R1,R2,R3=alkyl, aryl, benzyl; R4=aryl.

Heteroaromatic 2-pyridyl tosylates were successfully applied as electrophiles in palladium(0)-catalyzed Mizoroki-Heck-coupling reactions to electron-rich olefins with complete alpha-regioselectivity. This protocol represents a general strategy for the application of pyridyl tosylates and mesylates in the Mizoroki-Heck coupling. The catalytic system also proved adaptable to changes in the heteroaromatic core as well as large-scale applications. Finally, the synthetic utility of the functionalized alpha-heteroarylvinyl amides was established providing straightforward access to highly functionalized heteroaromatic compounds including chiral benzylic amide derivatives.

[reaction: see text] Conditions have been developed for the multicomponent synthesis of di- and tetrapeptide (7) based on the unique reactivity of alpha-isocyano acetic acid (4 and its alpha-substituted derivatives) by an Ugi four-component, five-center reaction. Simply mixing 4, a carbonyl compound (aldehyde or ketone, 8), and a secondary amine (9) (ratio: 1:1:2) in toluene in the presence of 1.5 equiv of ammonium chloride afforded the desired product in good to excellent yield as a mixture of two diastereomers.