Synthesis of Spiro[chromene-imidazo[1,2-a]pyridin]-3′-imines via 6-exo-dig Cyclization Reaction

Abstract

A transition-metal-free postmodification of the Groebke–Blackburn–Bienaymé (GBB) reaction for the synthesis of spiro­[chromene-imidazo­[1,2-a]­pyridin]-3′-imine was discovered. The unusual transformation represents the first example of activation and the reaction of the imidazole carbon atom. In this postcondensational modification, KOt-Bu acts as a base, which, after the isomerization of an alkyne moiety to allene, causes the next unique nucleophilic reaction of the imidazole carbon atom that results in spirocyclic structures. The proposed reaction mechanism was confirmed based on the DFT calculations.

Synthesis of Triazolo[4′,5′:4,5]furo[2,3-c]pyridine via Post Modification of an Unusual Groebke–Blackburn–Bienaymé Multicomponent Reaction

“…Recently, we demonstrated an undergraduate laboratory experiment wherein GBB-MCR-derived products were synthesized via in situ generated isocyanides from N -formylamines . The diverse fused heterocycles generated via GBB reaction include bicyclic imidazo­[1,2- a ]­pyridine, imidazo­[1,2- a ]­pyrimidine, imidazo­[1,2- a ]­pyrazine, imidazo­[2,1- b ]­thiazole, imidazo­[2,1- b ]­[1,3,4]­thiadiazole, imidazo­[1,2- b ]­[1,2,4]­triazole, imidazo­[1,2- b ]­pyrazol, and imidazo­[2,1- b ]­oxazole. − Various polycyclic scaffolds (1–11, Figure ) are also synthesized via post modification of the GBB-derived products. , Recently, we demonstrated that the one-pot-derived GBB products can be elaborated to fused polycyclic heterocycles (12–14) involving Pictet–Spengler cyclization (Figure ). …”

Synthesis of Imidazo[1,2-a]pyridine-Fused 1,3-Benzodiazepine Derivatives with Anticancer Activity via a One-Pot Cascade GBB-3CR/Pd(II)-Catalyzed Azide-Isocyanide Coupling/Cyclization Process

“…14 For example, a transitionmetal-free synthesis of spiro[chromene-imidazo[1,2-a]pyridin]-3′-imines was discovered by a post-GBB/6-exo-dig cyclization reaction under mild conditions. 15 Subsequently, Stahlberger and co-workers have developed a sequential synthesis route toward annulated imidazo [4,5-c]isoquinolines via a novel GBB-3CR/ imidoylative Hartwig−Buchwald amination sequence. 16 In the past decades, isocyanides and azides have been known as versatile synthetic intermediates in organic synthesis.…”

“…Recently, various post-condensation transformations of the GBB-3CR have become a powerful method in the synthesis of structurally diverse heterocyclic compounds . For example, a transition-metal-free synthesis of spiro­[chromene-imidazo­[1,2- a ]­pyridin]-3′-imines was discovered by a post-GBB/6- exo -dig cyclization reaction under mild conditions . Subsequently, Stahlberger and co-workers have developed a sequential synthesis route toward annulated imidazo­[4,5- c ]­isoquinolines via a novel GBB-3CR/imidoylative Hartwig–Buchwald amination sequence .…”

Transition-metal-free intramolecular double hydrofunctionalization of alkyne to access 6/7/5-fused heterocyclic skeletons

“…The previous observations and following our long-lasting interest in applying different types of isocyanides, 12 led us to design and synthesize a new class of functionalized isocyanides with an alkyne moiety. With the suitable choice of other components in the Groebke–Blackburn–Bienaymé (GBB) reaction, we wish to access the unprecedented 6/7/5-fused heterocyclic skeletons through intramolecular transition-metal-free double hydrofunctionalization (hydroamination and hydroalkoxylation) of nonactivated alkyne, which was completed upon preparative thin layer chromatography (PTLC) on silica gel plate.…”