Dedication
To Paul Knochel, whose creative genius has transformed functionalized organometallics
into a new form of molecular artistry.
Abstract
Isocyanoalkenes are a largely underexplored subset of isocyanides whose natural occurrence,
synthesis, and reactivity are elucidated in this review. The discussion begins with
an overview of the biosynthesis and natural occurrence, which provides a valuable
context for the synthetic approaches to these unusual π-substituted alkenes. Building
on this foundation, the review explores the characteristic reactivity of isocyanoalkenes,
which is shaped by the strong electron-withdrawing nature of the isocyanide group
and an almost complete lack of π-conjugation. Two primary modes of reactivity are
highlighted: conjugate additions – especially in systems containing additional electron-withdrawing
substituents – and radical additions to the isocyanide, often followed by annulation
via iminyl radical intermediates. Special attention is given to two particularly versatile
isocyanoalkenes – β-dimethylaminoisocyanoacetates and β-bromoisocyanoacetates – which
readily undergo nucleophilic addition–elimination–cyclization sequences to efficiently
assemble nitrogen-containing heterocycles. Overall, this review underscores the synthetic
potential of isocyanoalkenes and highlights their emerging value in the construction
of diverse heterocyclic scaffolds.
Keywords
Isocyanoalkenes - Synthesis - Reactivity - Additions - Heterocycles
