N,N‐Dimethylacetamide (DMA) as a Methylene Synthon for Regioselective Linkage of Imidazo[1,2‐a]pyridine

Abstract

Ac opper(II)-catalyzed oxidative methylene-bridged dimerizationo ft wo analogousi midazo[1,2-a]pyridines has been achieved using N,N-dimethylacetamide (DMA)a ss olvent cum methylene source.T hisr eactionw orks with av ariety of substituted imidazo[1,2-a]pyridines giving theirp roductsi n moderate to good yields. Isotopic labellinge xperiments revealed that the methylene group in the product originates from the N,N-dimethyl moiety of DMA.

Reaction Medium as the Installing Reservoir for Key Functionalities in the Molecules

“…Like earlier reports for the dimerization of imidazo pyridines, Kaswan et al . (2016) explored DMA as a source of methylene for the construction of bis‐imidazopyridines using vanadyl acetylacetonate catalyst iodobenzene diacetate (IBD) oxidant (Scheme ) .…”

“…A very similar reaction conditions as well mechanism was proposed by Modi et al . (2016) for the dimerization of imidazopyridines using DMA as methylene synthon (Scheme ) …”

Solvent‐Driven Iodine‐Mediated Oxidative Strategies for the Synthesis of Bis(imidazo[1,2‐a]pyridin‐3‐yl)sulfanes and Disulfanes

“…With an anticipation to synthesize sulfur‐bridged dimeric imidazo‐heterocycles, and following a trail from our recent report on phenyliodine diacetate (PIDA)‐mediated homocoupling of 2‐arylimidazo[1,2‐ a ]pyridines, we attempted the reaction of 2‐phenylimidazo[1,2‐ a ]pyridine ( 1 a ) with 3 equiv of sodium sulfide (Na 2 S) as a model reaction under PIDA‐mediated conditions (Table , entry 1). Sodium sulfide failed to participate in the reaction, and consequently 3,3′‐biimidazo[1,2‐ a ]pyridine– was obtained in a variety of solvents under reflux conditions over the targeted 3,3′‐bis(imidazo[1,2‐ a ]pyridin‐3‐yl)sulfane (entry 1). Moreover, PIDA‐mediated reaction of 1 a and Na 2 S in dimethyl sulfoxide (DMSO) or N , N ‐dimethylacetamide (DMA) failed to yield any product at all (entry 2).…”

Methylene Surrogates for the Synthesis of 3,3’‐Diindolylmethanes

“…Patel and co-workers synthesized methylene bridged imidazo [1,2a]pyridines using N,N-DMA as methylene synthon in the presence of Cu(OAc) 2 catalyst and K 2 S 2 O 8 as oxidant (Scheme 27). [33] Both symmetrical and unsymmetrical products can be obtained in high yields using this synthetic protocol.…”

“…As such, there are two essential bond cleavages, the first one is the CÀ H cleavage to generate an iminium ion while the second is the CÀ N cleavage in order to furnish the methenyl group (Scheme 38). Use of Cu(II) catalyst preferentially furnishes 3,3'-diindolylmethanes (32) while use of Co(II) in place of Cu(II) preferentially furnishes indole-3-carboxaldehydes (33) in the presence of a small amount of AcOH as additive.…”