Palladium‐Catalyzed Route to Three‐Component, One‐Pot Sequential Synthesis of Functionalized Cyclazines: 2,2a¹,4‐Triazacyclopenta[cd]indenes

Abstract

An efficient tandem route to the synthesis of 2,2a 1 ,4-triazacyclopenta[cd]indene derivatives of the cyclazine family has been developed. The target compounds were obtained in moderate to good yields by an ytterbiumA C H T U N G T R E N N U N G (III) triflate/palladium(II) acetate-catalyzed three-component domino reaction involving a palladium-catalyzed intramolecular aarylation of an a-aminocarbonyl functionality. This in turn will set the stage for a wide application of this useful reaction for the synthesis of structurally diverse polyheterocyclic skeletons containing the privileged imidazoA C H T U N G T R E N N U N G [1,2-a]pyridine structure.

Facile Synthesis of New Functionalized Triazacyclopenta[cd]indenones Through a Multicomponent Reaction Followed by an Intramolecular Aminolysis

“…The investigation was initiated with 4a as model substrates to optimize the reaction conditions, which was obtained via a GBB MCR according to the method previously described . Shaaban and Abdel‐Wahab recently also described the use of various salts and weak acids for GBB reaction .…”

“…Modifications on this scaffold are well documented in the literature; a frequently applied strategy is fusing the imidazo[1,2‐ a ]heterocycle motif with a heterocyclic moiety in order to design multiple biologically active agents . We have previously reported the synthesis of functionalized cyclazine, 2,2a 1 ,4‐triazacyclopenta[ cd ]indene by Groebke–Blackburn–Bienaymé (GBB) reaction, followed by in situ palladium(II) acetate‐catalyzed intramolecular cyclization . We herein wish to report the synthesis of a novel functionalized triazacyclopenta[ cd ]indenones, notably, such unique structural moiety is reported as platelet‐derived growth factor inhibitors(I, Scheme ) and corticotropin‐releasing factor receptor antagonists(II, Scheme ) .…”

Recent Developments in the Synthesis of Imidazo[1,2-a]pyridines

“…These products then reacted in the presence of palladium(II) acetate to give cyclazines 75 in good yields via intramolecular by C-H functionalization. 71 The same group reported an effective onepot sequential three-component reaction for the synthesis of 3H-1,2a 1 ,3-triazaacenaphthylenes 77 [Scheme 27 (b)]. The tandem three-component reaction involves the ytterbium(III) triflate catalyzed Groebke-Blackburn-Bienaymélike condensation of 6-alkynyl-2-aminopyridines 76, aldehydes 59, and isocyanides 60, which is followed by intramolecular nucleophilic attack of amine in a 6-endo-dig fashion in the presence silver carbonate to afford fused imidazo[1,2-a]pyridines 77.…”

Metal Free Formation of Various 3-Iodo-1H-pyrrolo[3′,2′:4,5]imidazo-[1,2-a]pyridines and [1,2-b]Pyridazines and Their Further Functionalization

“…Furthermore, imidazo­[1,2- a ]­pyridines are known to exhibit a broad range of biological activities . On the basis of our background in the synthesis and functionalization of imidazo­[1,2- a ]­pyridines, we investigated the formation of tri or tetracyclic fused imidazo­[1,2- a ]­pyridines . Apart from condensation or metal catalyzed amination, electrophilic cyclization on alkyne was recently investigated as a secondary transformation.…”