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The present review provides a broad description of the methods reported for the synthesis of α-acyloxy ketones and some of their derivatives. α-Acyloxy ketones and their derivatives are vital synthetic intermediates and are ubiquitous as biochemical constituents of living organisms, biologically active natural products and pharmaceuticals. Due to their biological importance, new methods for their synthesis are being continuously developed and documented in the recent past. However, the chemical literature lacks a comprehensive summary on the synthetic methodologies targeting α-acyloxy ketones. In an attempt to fill this void, this review discusses their synthetic procedures developed over time. The synthetic approaches are systematically classified based on the substrates used. The mechanistic details for certain critical cases are also discussed. In the past, preparation of α-acyloxy ketones was reported from functionalized ketones like α-haloketones and diazo esters. Later on, among the reactions that formed the acyloxy ketones, oxidative coupling of ketones with carboxylic acids both under metal and metal-free conditions made their synthesis simple and versatile. Specifically, in the last decade, many oxidative coupling reactions emerged as a powerful tool for the synthesis of α-acyloxy ketones. Quite recently, acyloxy ketones' synthesis has been reported from commercially available alkenes and alkynes through oxidative addition reactions. Subsequently, the mechanistic details for these coupling reactions became interesting to many organic chemists. The asymmetric version of the title compounds hails from their enzymatic resolution to metal catalysed chiral synthesis. Besides, the synthesis of acyloxy ketones from epoxides, alcohols and enamides using various oxidative reagents has also been documented.

Simple and inexpensive polyhalides (CCl4 and C2Cl6 ) have been found to be effective and versatile oxidants in removing electrons from Breslow intermediates under N-heterocyclic carbene (NHC) catalysis. This oxidative reaction involves multiple single-electron-transfer (SET) processes and several radical intermediates. The α, β, and γ-carbon atoms of aldehydes and enals could be readily functionalized. Given the low cost of the oxidants and the broad applicability of the reactions, this study is expected to greatly enhance the feasibility of oxidative NHC catalysis for large-scale applications. Also this new SET radical process with polyhalides as single-electron oxidants will open a new avenue in the development of NHC-catalyzed radical reactions. Accepted version We acknowledge financial support from the National Natural Science Foundation of China (No. 21132003; No. 21472028), Singapore National Research Foundation (NRF-NRFI2016-06), the Ministry of Education of Singapore (MOE2013-T2-2-003), Nanyang Technological University (NTU, Singapore), China's Ministry of Education, Thousand Talent Plan, Guizhou Province Returned Oversea Student Science and Technology Activity Program, Science and Technology of Guizhou Province, and Guizhou University.

A concise enantioselective synthesis of 1,4-dideoxy-1,4-imino- d -arabinitol, (+)-DAB-1, has been described in good overall yield (18.1%) and with high enantiomeric purity (up to 98% ee) starting from a simple raw material, cis -2-butene-1,4-diol. The Co-catalyzed hydrolytic kinetic resolution of a two-stereocentered racemic azido epoxide followed by asymmetric dihydroxylation of the alkene and ‘one pot’ reductive cyclisation of the azido diol are key reactions in the synthetic sequence.

An unprecedented conversion of alkenes and enol ethers to the corresponding α-imido carbonyl compounds with excellent regioselectivity and yields has been developed. This oxo-amination process employs readily available N-bromosuccinimide (NBS) and secondary amines as N-sources and dimethyl sulfoxide (DMSO) as the oxidant and also leads to the production of amino alcohols in a single step on reduction, thus broadening the scope of this operationally simple reaction. For the first time, the formation of reactive Me2S(+)-O-Br species generated by the interaction of NBS with DMSO has been proven.

A novel, N-heterocyclic carbene (NHC) catalyzed direct oxidative coupling of styrenes with aldehydes has been described for the synthesis of α,β-epoxy ketones in good yields. This unprecedented regioselective oxidative coupling employs NBS/DBU/DMSO (DBU=1,8-diazabicyclo [5.4. 0] undec-7-ene, DMSO=dimethylsulfoxide, NBS=N-bromosuccinimide) as an oxidative system at ambient conditions. Additionally, first NHC-catalyzed Darzens reaction of α-bromoketones and aldehydes under mild reaction conditions has also been described. Interestingly, mechanistic studies have revealed the preferred reactivity of NHC with alkene/α-bromoketone rather than aldehydes, thus proceeding via the ketodeoxy Breslow intermediate.

5 p. A carbene-catalyzed intermolecular C−N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused β-lactones, is disclosed. The nitrogen-containing bicyclic β-lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene-catalyzed asymmetric carbon–heteroatom bond-forming reactions. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version

An unprecedented conversion of alkenes and enol ethers to the corresponding α-imido carbonyl compounds with excellent regioselectivity and yields has been developed. This oxo-amination process employs readily available N-bromosuccinimide (NBS) and secondary amines as N-sources and dimethyl sulfoxide (DMSO) as the oxidant and also leads to the production of amino alcohols in a single step on reduction, thus broadening the scope of this operationally simple reaction. For the first time, the formation of reactive Me2S(+)-O-Br species generated by the interaction of NBS with DMSO has been proven.

A high-yielding synthesis of α-acyloxyketones using a N-heterocyclic-carbene (NHC)-catalyzed, oxidative ring-opening of epoxides with aromatic aldehydes is described. This regioselective, oxidative process utilizes a N-bromosuccinimide (NBS)/DMSO combination as the oxidant system and Et3N as the base under mild reaction conditions.

NBS/DBU/DMSO is used as oxidative system for the regioselective oxidative coupling reactions.

The simple regioselective oxo-acyloxylation process of alkenes and enol ethers with carboxylic acids provides α-acyloxyketones and esters.

A simple protocol is described for the oxidative transformation of aldehydes to the corresponding organotin(IV) carboxylates in high yields (up to 90%) that utilizes atmospheric O 2 as the sole oxidant, N -heterocyclic carbene as catalyst (at 10 mol %), and tributyl tin chloride as stannylating agent. The uniqueness of the reaction lies in the direct conversion of aldehydes to the corresponding organotin(IV) carboxylates via stannylation of carboxylic acids, generated from the reaction of a Breslow intermediate with O 2 .

I2-catalyzed oxo-acyloxylation of alkenes and enol ethers with carboxylic acids providing for the high yield synthesis of α-acyloxyketones and esters is described. This unprecedented regioselective oxidative process employs TBHP and Et3N in stoichiometric amounts under metal-free conditions in DMSO as solvent. Additionally, I2-catalysis allows the direct hydroxy-acyloxylation of alkenes with the sequential addition of BH3·SMe2 leading to monoprotected diol derivatives in excellent yields.

A novel organocatalytic process for the facile synthesis of α-acyloxycarbonyl derivatives via an oxo-acyloxylation of alkenes with aromatic aldehydes is developed.

Aerobic oxidation followed by stannylation of the resulting carboxylic acids allows the preparation of the target compounds.

An N-heterocyclic carbene (NHC)-catalyzed reaction of alkenes with aromatic aldehydes providing for a high yield synthesis of α-acyloxy ketones and esters has been described. This unprecedented regioselective oxidative process employs NBS and Et3N in stoichiometric amounts and O2 (1 atm) as an oxidant under ambient conditions in DMSO as a solvent.