Palladium-Catalysed Synthesis and Transformation of Quinolones

Abstract

Palladium-catalysed reactions have had a large impact on synthetic organic chemistry and have found many applications in target-oriented synthesis. Their widespread use in organic synthesis is due to the mild conditions associated with the reactions together with their tolerance of a wide range of functional groups. Moreover, these types of reactions allow the rapid construction of complex molecules through multiple bond-forming reactions in a single step, the so-called tandem processes. Pd-catalysed reactions have been applied to the synthesis of a large number of natural products and bioactive compounds, some of them of complex molecular structures. This review article aims to present an overview of the most important Pd-catalysed reactions employed in the synthesis and transformations of quinolin-2(1H)-ones and quinolin-4(1H)-ones. These compounds are widely recognized by their diverse bioactivity, being privileged structures in medicinal chemistry and useful structural moieties for the development of new drug candidates. Furthermore, they hold significant interest due to their host–guest chemistry; applications in chemical, biochemical and environmental analyses and use in the development of new synthetic methods. In some cases, the quinolone formation step cannot be ascribed to a claimed Pd-catalysed reaction but this reaction is crucial to get the appropriate substrate for cyclization into the quinolone. Herein we present and discuss different economical, efficient and selective synthetic strategies to access quinolone-type compounds.

Palladium‐Catalyzed [3+2] and [2+2+2] Annulations of 4‐Iodo‐2‐quinolones with Activated Alkynes through Selective C−H Activation

“…In summary,w eh aves uccessfully developedt he palladiumcatalyzed annulation of 4-iodo-2-quinolones with activated internal alkynes involving CÀHa ctivation. 4-Iodoquinolones were treated with activated alkynes,s uch as DMAD in the presence of Pd(OAc) 2 and Ag 2 CO 3 in DMF at 100 8Ct op roduce the [3+ +2] annulation products( cyclopenta[de]quinoline-2(1 H)-ones) through aromatic CÀHa ctivation along with the [2+ +2+ +2] annulationp roducts (phenanthridine-6(5 H)-ones) by vinylic CÀH activation.T he product selectivity ([3+ +2] vs. [2+ +2+ +2]) varied depending on the substituents on the benzene ring of the quinolone substrate, the activated alkyne, and the reactionc onditions. It wasf ound that 4-iodo-2-quinolonei sa ne xceptional substrate for the present palladium-catalyzed annulation;4 -iodoquinoline and 3-iodo-4-quinolone all failed to undergo the annulation, and 4-iodo-1,8-naphthyridin-2(1 H)-one,4 -iodocoumarin, and 4-iodo-1-isoquinolone exhibited diminished reactivity.W ea lso investigated the individual steps in the catalytic cycle by using DFT calculations on model 4-iodo-2-quinolones.…”

“…[1] Therefore, various synthetic methods have been reported for the synthesis of 2-quinolone derivatives. [2] However,t he discovery of an unprecedented synthetic route is stilli mportantt oward the identificationo fn ovel bioactive 2-quinolones. In this regard, we have reported the modular assembly of 3,4-fused 2-quinolones and 4-aryl-2-quinolones by using suitably protected (ortho-aminophenyl)propiolates as buildingb locks.…”

Recent Developments in the Synthetic Strategies of 4‐Quinolones and Its Derivatives

“…The mechanism of the reaction is shown in figure 9. [52] A facile metal-free approach for the synthesis of 3-(Iso) quinolinyl 4-quinolones (40) from (Iso) quinoline N-oxides (39) and ynones (38) was developed by Zhang and co-worker. The optimized reaction conditions involved the condensation between ynone (38, 0.3 mmol) and (Iso) quinoline N-oxides (39, 0.45 mmol) in the presence of 0.5 equivalent of hydrochloride (12.5 μL of 12 mol L À 1 HCl solutions) in 0.5 mL of DMF in a sealed tube at 140°C to provide the best yields of the final compounds [scheme 13].…”

“…[37] Silvia et al cover the palladium-catalyzed synthesis of 4-quinolones. [38] Jiang et al reviewed the antibacterial activity of 4-quinolones [39] while Naeem et al reviewed the method of synthesis and antibacterial activity of quinolones. [40] The current review describes the various advances made in the synthesis of 4-quinolones and its derivatives using metal catalysis, metal-free synthesis, and visible light assisted synthesis.…”

Recent Advances in One-Pot Modular Synthesis of 2-Quinolones

“…Nishiwaki reviewed synthetic methodologies for nitroquinolones and examples of elaborative synthetic application using them [ 82 ]. A comprehensive review by Silva covered palladium-catalyzed reactions for 2- and 4-quinolone synthesis, some of which are one-pot methods for the preparation of 2-quinolones [ 83 ]. This focused review aims to provide an extensive survey of recently developed one-pot intermolecular reactions to prepare functionalized 2-quinolone derivatives; it limits the scope to examples involving the construction of the core structures but not including mere functionalization of 2-quinolones.…”