Ru-Catalysed synthesis of fused heterocycle-pyridinones and -pyrones

Abstract

The synthesis of fused heterocycle-pyridinones has been achieved by oxidative coupling of N-unprotected primary heterocycle-amides with internal alkynes. The reaction, which is catalysed by Ru(ii) and assisted by Cu(ii), takes place through C-H and N-H bond activation of the heterocyclic unit. The scope of the reaction includes a variety of alkynes, electron-rich thiophenes, furans and pyrroles, and even electron-poor pyridines. The reaction is fully regioselective with respect to the position of the C-H bond activation due to the directing effect of the amide group. In the same way, the synthesis of fused heterocycle-pyrones (isocoumarins) has been developed by Ru-catalysed oxidative coupling of heterocyclic carboxylic acids and internal alkynes. The reaction involves C-H and O-H bond activation. This reaction also has a broad scope, from electron-rich thiophenes, furans and pyrroles to electron-deficient pyridines and quinolines.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…Similar, but Ru catalysed cyclisations have been disclosed by the groups of Swamy 220 and Urriolabeitia (not shown). 221 The former one used chromene-3-carboxamides as substrates, the latter one various heterocyclic amides. Hence, in both cases a pyridinone ring was annulated to another heterocyclic ring, giving access to interesting scaffolds.…”

Rhodium(III)‐Catalyzed Formal Cycloaddition between Thienopyridine/Thienopyrazine Carboxylic Acids and Alkynes, Triggered by C−H Activation

“…The reaction required a high amount of the Ru dimer precatalyst (10 mol %), and was only effective with aliphatic alkynes. Thus, in presence of diphenylacetylene as coupling partner the reaction only gave a 10 % yield of the expected cycloadduct [7c] . More recently, Wu, Shang et al .…”

“…Especially attractive are those reactions in which the directing group is also engaged in the bonding process, as this can lead to formal cycloaddition reactions [6a,b,7a–e] . This is the case with benzoic acids, that can participate as four‐atom components in catalytic cycloadditions with alkynes to give isocoumarins, in a formal (4+2) process (Scheme 1a) [8a–b] .…”

Ruthenium-catalyzed C–H bond functionalization in cascade and one-pot transformations

“…), NaOAc (2 equiv.) operating in toluene at 120 °C during 24 h. From 1-methyl-2-phenylethyne and 1,2-diphenylethyne, the corresponding alkenylated thieno[2,3-c]pyridin-7(6H)-ones were isolated in 28 and 19% yield, respectively [86]. Scheme 18.…”