Introducing an α-Keto Ester Functional Group through Pt-Catalyzed Direct C–H Acylation with Ethyl Chlorooxoacetate

Abstract

Platinum-catalyzed selective C–H acylation of 2-aryloxypyridines with ethyl chlorooxoacetate provides an efficient way of introducing an α-keto ester functional group. The reaction is oxidant-free, additive-free, and, more significantly, free of any decarbonylative side reactions. The reaction tolerates a variety of substituents from strongly electron-donating to strongly electron-withdrawing groups. Double acylation is feasible for 2-phenoxypyridine and its derivatives with only one substituent at the para position. Although the reaction of 2-(2-methylphenoxy)­pyridine with ethyl malonyl chloride did not produce the desired β-keto ester, the reaction with ethyl succinyl chloride proceeded smoothly to give the γ-keto ester. Ethyl chlorooxoacetate is much more reactive than ethyl succinyl chloride in this Pt-catalyzed C–H acylation reaction.

Isomerization-Induced Multiple Reaction Pathways in Platinum-Catalyzed C–H Acylation Reaction of 2-Aryloxypyridines

“…Recently, we discovered the acylation of cycloplatinated complexes derived from tridentate cyclometalating ligands 6-arylamino-2,2′-bipyridine, 6-phenoxy-2,2′-bipyridine, 6-phenylthio-2,2′-bipyridine, and 6-benzyl-2,2′-bipyridine . Based on the discovery, we developed an oxidant- and additive-free, platinum-catalyzed ligand-directed C–H acylation reaction of 2-aryloxypyridines, which provides an efficient way to introduce an acyl group to the ortho -position of the 2-aryloxypyridines and allow the synthesis of aryl aryl ketones, aryl alkyl ketones, α,β-unsaturated ketones, α-keto esters, and γ-keto esters (Scheme ). The reaction is believed to proceed through two distinct steps: cycloplatination (C–H activation) and acylation of the platinacycle (functionalization).…”

Applications of Oxone® in Organic Synthesis: An Emerging Green Reagent of Modern Era

“…α-Ketoesters and 1,2-diketones possesses a great consequence for the synthesis of diverse pharmaceuticals as well as other interesting organic molecules. [303][304][305] They are broadly used as starting materials for the intercalation reactions, production of carboxylic acids, heterocyclic compounds and also for the asymmetric synthesis of α-hydroxy ketones. 1,2-Diketones also have fascinating applications as photosensitive agents and photoinitiators.…”