Palladium-Catalyzed Synthesis of Fluorescent Benzo[4,5]imidazo[1,2-a]pyridines through Annulation Reaction of Benzimidazoles and Alkynyl Bromides with Internal Alkynes

Abstract

An efficient synthesis of fused azapolycycles based on (benz)imidazole and pyridine scaffolds has been developed. In all cases, the first nucleophilic addition of (benz)imidazoles to alkynyl bromides in tert-pentyl alcohol can proceed in a stereoselective manner to provide (Z)-N-(1-bromo-1-alken-2-yl)benzimidazoles at 110 °C. Sequentially, these adducts containing alkenyl bromide can undergo Pd-catalyzed intermolecular C−H annulation in the presence of internal alkynes in dimethylacetamide, affording fluorescent (benz)imidazole-fused pyridines in good to high yields. These compounds generally exhibit blue or green fluorescences (454−503 nm for solution states and 472−506 nm for solid states), and the fluorescence quantum yields remained in 0.19−0.89 and 0.02−0.74 for solution and solid states, respectively.

Benzo[4,5]imidazo[1,2-a]pyridines and benzo[4,5]imidazo[1,2-a]pyrimidines: recent advancements in synthesis of two diversely important heterocyclic motifs and their derivatives

“…In 2020, Chunxia Chen and and co-workers reported the Pd-catalyzed intermolecular C–H annulation using benzimidazole ( 177 ), alkynyl bromide ( 178 ), and alkyne ( 179 ) to construct π-extended benzimidazole-fused pyridine ( 180 ) by a two-step process (Scheme 24). 47 Initially, the reaction was carried out by taking benzimidazole, bromoethynylbenzene, diphenylacetylene, and the reaction condition was optimized for the two steps separately. For the first step, using tert -pentyl alcohol as a solvent, Cs 2 CO 3 as a base at 110 °C were found to be the best conditions.…”

“…For example, by photostimulated cyclization of 2-(2-halophenylamino)pyridines in liquid ammonia, 42 by NHC catalysis, 43 by ruthenium-catalyzed cyclization of o-alkynylaldehydes and substituted benzenediamines 44 and intramolecular C-H amination of N-arylpyridin-2-amines. 45,46 Several other methods have also been developed which are catalyzed by a variety of metals such as Palladium, [47][48][49] rhodium, 50,51 and Copper. [52][53][54][55][56][57] Greener alternatives have also been developed such as those being mediated by Iodine.…”

Simple inorganic base promoted polycyclic construction using mucohalic acid as a C3 synthon: synthesis and AIE probe application of benzo[4,5]imidazo[1,2-a]pyridines

“…Now, many methods have been developed for the preparation of benzo[4,5]imidazo[1,2- a ]-pyridines. Generally, intramolecular or intermolecular tandem C–N coupling/annulation reactions catalyzed by the transition-metal Pd 12 or Cu 13 are the main methods. The oxidative C–H cyclic amination reaction promoted by hypervalent iodine( iii ) or other strong oxidants has provided an alternative synthetic strategy.…”

Cs2CO3-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

“…Of particular synthetic value is the addition to the triple bond of bromoacetylenes to provide vinyl adducts, which can undergo numerous transformations. For example, bromoacetylenes were demonstrated to add imidazoles, imidazolines [ 12 ], and benzimidazoles [ 13 – 14 ] to give vinyl bromides. Sulfonamides reacted with bromoacetylenes to deliver N -bromovinyl- p -toluenesulfonamides that under Heck reaction conditions afforded N -( p -toluenesulfonyl)pyrroles [ 15 ].…”