An Efficient and Metal–free Synthesis of α‐Ketoesters via Oxidative Cross Coupling of Arylglyoxals with Alcohols

Abstract

An efficient and metal‐free protocol has been developed for the synthesis of α‐ketoesters via oxidative cross coupling of arylglyoxals with alcohols by using N‐bromosuccinimide as an oxidant and 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene (DBU) as a base. The process involves cleavage of a C−H bond and construction of a C−O bond. Mild reaction conditions, short reaction time, broad substrate scope, operational simplicity and good to excellent yields of the products are remarkable features of this method.

Metal-Free Oxidative Esterification of Ketones and Potassium Xanthates: Selective Synthesis of α-Ketoesters and Esters

“…Traditional approaches for constructing α-ketoesters include esterification of α-ketoacyl halides or α-ketoacids, oxidation of α-hydroxy esters, etc., but these approaches suffer from problems such as low conversion, large amounts of byproducts, and limited substrate scope. In recent years, effective approaches to synthesize α-ketoesters have gradually emerged, such as oxidative dehydrogenative coupling of α-carbonyl aldehydes and alcohols, decyanation esterification of β-ketonitriles, copper-catalyzed aerobic oxidation of (hetero)­aryl acetimidates, and oxidative esterification via C–C bond cleavage . Some of these approaches require the use of transition-metal catalysts, hypervalent iodine reagents, or difficult-to-prepare raw materials.…”

Novel Effect of Zinc Nitrate/Vanadyl Oxalate for Selective Catalytic Oxidation of α-Hydroxy Esters to α-Keto Esters with Molecular Oxygen: An In Situ ATR-IR Study

“…For example, phenylglyoxylate and its derivatives are used as key intermediates for synthesis of herbicide metamitron [2], and pyruvate and its derivatives can be employed for the preparation of pharmaceutical pindolol and pesticides thiabendazole [3]. In the past several decades, several methods for synthesis of α-keto esters have been reported, such as esterification of α-keto acids or α-carbonyl aldehydes, oxidative cleavage of β-diketones, oxidative esterification of aryl-ketones and so on [4,5,6]. Considering the excellent atom efficiency, there is a growing interest to develop efficient catalytic oxidation of α-hydroxy esters into their corresponding α-keto esters [7,8].…”

Heterogeneous Esterification from α-Hydroxy Ketone and Alcohols through a Tandem Oxidation Process over a Hydrotalcite-Supported Bimetallic Catalyst

“…α-Keto esters, as key structural motifs, have been found in various biologically active compounds, pharmaceuticals, and anticancer agents. − Moreover, α-keto esters are important precursors in organic synthesis, such as in asymmetric reduction, aminohydroacylation, and aldol reactions. − Therefore, the efficient synthesis of α-keto esters in a straightforward way is of great importance. Traditional synthetic methods involve esterification of α-ketoacyl derivatives, direct oxidation of α-hydroxy esters, and Pd-catalyzed carbonylation using CO. − In recent years, acetophenone was directly used as a substrate to react with alchohols for the synthesis of α-keto esters in the presence of copper salts or I 2 . − Additionally, Jiao and co-workers reported a method for the synthesis of α-keto esters using α-carbonyl aldehydes and alcohols as raw materials and catalyzed by copper with pyridine as an additive. − Novel synthetic approaches involving copper-catalyzed C–C or C–N oxidative cleavage have also emerged. , However, stoichiometric amounts of iodide reagents, additives, ligands, and peroxide (e.g., tert -butyl hydroperoxide) were inevitably employed in the previous methods. From a green and environmental perspective, the development of an atom-economical oxidative esterification for the synthesis of α-keto esters based on a recyclable heterogeneous catalyst using oxygen as a green oxidant is highly desirable and challenging.…”