Oxidative esterification of aldehydes

Esters are very useful chemical intermediates, in terms of atom economy and versatility, and can be helpful in further transformations. Esterification is one of the fundamental transformations in organic synthesis and is widely used in laboratories and industry [1]. Oxidative esterification of aldehydes with alcohols is an attractive method for the synthesis of esters because aldehydes are readily available raw materials on a commercial scale. Although several facile and selective esterification reactions have been reported [2], the development of a catalytic method for the direct oxidative esterification of aldehydes with alcohols under mild and neutral conditions in the presence of molecular oxygen as the terminal oxidant is highly desirable from both economic and environmental aspects. 

I 13 Aerobic Oxidative Esterification of Aldehydes with Alcohols... 

The oxidative esterification of aldehydes in the presence of alcohols to produce saturated and unsaturated aliphatic esters has been developed at the Nippon Shokubai laboratories a great result is represented by the new synthesis of methylmethacrylate (MMA) from methacrolein, methanol and molecular oxygen, which allows yields up to 50 mol MMA (kg cat)" h" using supported bimetallic gold catalysts under relatively mild conditions (80 °C and 3 MPa) [7]. 

The Breslow intermediates are quite unstable toward oxidative conditions, providing acyl imidazolinium species that can acylate several nucleophiles or suffer 1,4-conjugated additions. Gois et al. disclosed the oxidative esterification of aldehydes using an iron/NHC catalytic system to prepare benzoic and cinnamic esters using phenols as nucleophiles (Scheme 26.11)... 

Palladium catalysts are widely used in liquid phase aerobic oxidations, and numerous examples have been employed for large-scale chemical production (Scheme 8.1). Several industrially important examples are the focus ofdedicated chapters in this book Wacker and Wacker-type oxidation of alkenes into aldehydes, ketones, and acetals (Scheme 8.1a Chapters 9 and 11), 1,4-diacetoxylation of 1,3-butadiene (Scheme 8.1b Chapter 10), and oxidative esterification of methacrolein to methyl methacrylate (Scheme 8.1c Chapter 13). In this introductory chapter, we survey a number of other Pd-catalyzed oxidation reactions that have industrial significance, including acetoxylation of ethylene to vinyl acetate (Scheme 8. Id), oxidative carbonylation of alcohols to dialkyl oxalates and carbonates (Scheme 8.1e), and oxidative coupling of dimethyl phthalate to 3,3, 4,4 -tetramethyl biphenylcarboxy-late (Scheme 8.1f). 

The preparation of a,p-epo)ty esters was developed by Yan and coworkers via one-pot epoxidation and subsequent oxidative esterification. The product was applied in the synthesis of (—)-clausenamide (Scheme 8.42). At the same time, Jorgensen also published a one-pot Michael addition/oxidative esterification of a,p-unsaturated aldehydes. ... 

An unexpected oxidative esterification of cinnamaldehydes by cinnamyl bromides is catalysed by a simple NHC, A,A -dibenzyl-benzimidazolium chloride, in up to 86% yield in DBU, using dioxygen or Mn02 as oxidant. The mechanism has been probed by 0-labelling, and neither cinnamyl nor cinnamate moieties undergo cis-trans isomerization during the process. The reaction has been successfully extended to other aldehydes, although electron-rich cases are poor substrates. ... 

Furthermore, the first enantioselective oxidative esterification of simple aldehydes... 

A mechanistic investigation of aerobic esterifications of aldehydes with alcohols using NHC catalysis indicates that it is the benzoin that undergoes oxidation, and not the Bres-low intermediate, nor the NHC-aldehyde tetrahedral adduct. ... 

Cinnamils (162) have surprisingly been found to evolve towards 2,3,8-triaryl vinyl fulvenes (163) and o-terphenyl derivatives (164) under NHC catalysis. The formation of these products has been rationalized via a mechanism involving a complex cascade process. Finally, a mechanistic investigation has been carried out on the NHC-catalysed aerobic oxidative esterification of aromatic aldehydes.Aryloin species have not only been identified as key intermediates of such oxidative reactions, but most importantly is that they have been shown to be the species which react with oxygen in the air and not the Breslow intermediates as previously suggested. 

Table 224. Oxidative esterification of alcohols/aldehydes using Au-based supported catalysts.

The resurgence of interest in NHC as catalysts in the last 6 years led several chemists to reinvestigate external oxidants for the azolium-catalyzed esterification of aldehydes. Using cyanide, which shares many similarities to azolium salts in its reactions with aldehyde, Corey had shown in 1968 that the combination of an aldehyde and sodium cyanide in the presence of Mn02 and an alcohol led to esters. Scheldt executed this work with triazolium carbene as a promoter, leading to similar results (Scheme 14.9). Other oxidants including TEMPO radicals (2,2,6,6-tetramethylpiperidine 1-oxyl) and azobenzene" were also found suitable for NHC-catalyzed oxidative esterifications. 

Oxidation. The oxidation of acid sensitive alcohols with Chromium(VI) Oxide in HMPA is one example of the use of HMPA in oxidation reactions. (CAUTION Do not crush CrOs prior to reaction since violent decomposition can occur. The use of DMPU has been reported to have a similar hazardous effect). Recently, a Bromine/NaHCOs/HMPA system was used for the oxidative esterification of alcohols with aldehydes, where the HMPA considerably accelerated the oxidation by bromine and lowered the rate of unwanted halo-genation. Epoxidations of alkenes or allylic alcohols have been accomplished using M0O5 HMPA-pyridine (Oxodiperoxymolyb-denum(pyridine)(hexamethylphosphoric triamide) MoOPH). ... 

Oxidation. Oxidation of the -amyl alcohols produces aldehydes, which after continued oxidation can yield acids. This route to aldehydes has httle merit. However, oxidative esterifications with alkah metal hypohaUtes (eg, calcium chlorite, Ca(OCl)2) (49), bromates (eg, sodium bromate, NaBrO )... 

The simple cleavage of lactones 1 or 2 with alcohol and acid has not been reported. However, when 1 is treated with benzaldehyde diethyl acetal and hydrochloric acid, ethyl 3,5 4,6-di-0-benzylidene-L-gulonate (47) is formed in >90% yield.77,78 No other isomers were observed, and other acetals of benzaldehyde, as well as aliphatic aldehydes, afford similar products in good yield.77 D Addieco prepared36 similarly protected derivatives of L-gulonic acid by oxidation of l,3 2,4-di-0-ethylidene-D-glucitol (15), followed by esterification of the resulting acid with diazomethane. 

Oxidative cleavage of the terminal double bond of 49 by ozonolysis to the aldehyde followed by permanganate oxidation to the acid and esterification with diazomethane produced the methyl ester 50. Dieckmann cyclisation of 50, following the procedure developed in Holton s laboratory (LDA, THF, -78 °C, 0.5 h, then HOAc, THF), gave the enol ester 5J in 93% yield (90% conversion). Decarbomethoxylation of 5J. was carried out by temporarily protection of the secondary alcohol (p-TsOH, 2-methoxypropene, 100%), and heating the resulting compound 52 with PhSK in DMF, at 86 °C (3 h) to provide 53a or, after an acidic workup, the hydroxy ketone 53b. 92% yield. 

Properties. Vanillin is a colorless crystalline solid mp 82-83 °C) with a typical vanilla odor. Because it possesses aldehyde and hydroxyl substituents, it undergoes many reactions. Additional reactions are possible due to the reactivity of the aromatic nucleus. Vanillyl alcohol and 2-methoxy-4-methylphenol are obtained by catalytic hydrogenation vanillic acid derivatives are formed after oxidation and protection of the phenolic hydroxyl group. Since vanillin is a phenol aldehyde, it is stable to autoxidation and does not undergo the Cannizzarro reaction. Numerous derivatives can be prepared by etherification or esterification of the hydroxyl group and by aldol condensation at the aldehyde group. Several of these derivatives are intermediates, for example, in the synthesis of pharmaceuticals. 

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