Microwave‐Assisted, Rhodium(III)‐Catalyzed N‐Annulation Reactions of Aryl and α,β‐Unsaturated Ketones with Alkynes

Abstract

New Rh(III)-catalyzed, one-pot N-annulation reactions of aryl and α,β-unsaturated ketones with alkynes in the presence of ammonium acetate have been developed. Under microwave irradiation conditions, the processes lead to rapid formation of the respective isoquinoline and pyridine derivatives with efficiencies that are strongly dependent on the steric nature of the aryl ring and enone substituents. By employing this protocol, a variety of isoquinoline and pyridine derivatives were prepared in high yields. In addition, a new one-pot approach to the synthesis of pyridines, involving four-component reactions of ketones, formaldehyde, NH(4)OAc, and alkynes, has been uncovered. This process takes place through a route involving initial aldol condensation of the ketone with formaldehyde to generate a branched α,β-unsaturated ketone that then undergoes Rh(III)-catalyzed N-annulation with NH(4)OAc and the alkyne

Benefits and applications of microwave-assisted synthesis of nitrogen containing heterocycles in medicinal chemistry

“…al. 46 investigated a novel MW-promoted, one-pot reaction of aryl and a,b-unsaturated ketones 52, alkynes 53 and ammonium acetate 54 to produce N-annulated pyridine derivatives 55 bearing diverse cyclic substituents (eqn (16)). This protocol allows for the synthesis of "crowded" pyridines in high yields, and thus bypasses steric effects, which typically decrease the efficiency of their synthesis.…”

C–H Activation and Alkyne Annulation via Automatic or Intrinsic Directing Groups: Towards High Step Economy

“…In 2014, Jun et al . developed a microwave‐assisted pyridine synthesis via four‐component reaction of ketones, paraformaldehyde, NH 4 OAc and alkynes, in which the α,β ‐unsaturated ketones are auto‐formed by condensation to further improve the step economy …”

Rh(III)-Catalyzed One-Pot Three-Component Diannulation of Benzils, Ammonium Acetate, and Alkynes to Build 1,1′-Biisoquinolines

“…In recent decades, transition-metal-catalyzed C–H annulations of oximes, imines, hydrazone, azines, and azides to construct isoquinolines (half-structure of BIQs) have been well established. Considering these examples still need an extra step to install the directing groups (DGs), Hua, Zhang, Jun, and Ackermann realized one-pot isoquinoline synthesis by three-component reactions of aryl ketones, N sources, and alkynes. However, one-pot access to 1,1′-BIQs from all commercially available agents via C–H annulations has not been reported.…”