Four-Component Cascade
Heteroannulation of Heterocyclic
Ketene Aminals: Synthesis of Functionalized Tetrahydroimidazo[1,2‑<i>a</i>]pyridine Derivatives
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Abstract
An efficient and straightforward four-component synthetic
protocol
has been developed to synthesize imidazo[1,2-<i>a</i>]pyridines
and imidazo[1,2,3-<i>ij</i>][1,8]naphthyridine derivatives
incorporating medicinally privileged heterosystems from heterocyclic
ketene aminals, aldehydes, diketene, and amines via cascade reactions,
including diketene ring-opening, Knoevenagel condensation, aza–ene
reaction, imine–enamine tautomerization, cyclocondensation,
and intramolecular S<sub>N</sub>Ar. This strategy can provide an alternative
approach for easy access to the highly substituted imidazo[1,2-<i>a</i>]pyridine derivatives in moderate to good yields using
four simple and readily available building blocks under mild conditions.
Importantly, the unusual splitting peaks in the <sup>1</sup>H NMR
spectra of the products derived from heterocyclic ketene aminals with
an <i>o</i>-halogen atom on the aryl ring were explained
reasonably by varying the temperature in NMR analysis