Acyl anions benzoin condensation

The dithiane anion 1.9 also reacts with acyl halides, ketones and aldehydes to give the corresponding dioxygenated compounds. Schemes 1.4 and 1.5 show the reaction of dithiane anions 1.11 and 1.12 with ketones. The most common example of umpolung reactivity of a carbonyl group is the benzoin condensation (Scheme 1.6). 

The thiazolium-catal)fzed addition reactions of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) and the benzoin condensation (most often between two aldehydes) are well-known synthetic tools leading to the synthesis of highly funtionalized... 

The mechanism of the benzoin condensation, as depicted in Scheme 1, suggested that anions derived from a protected aldehyde cyanohydrin should function as nucleophilic acylating reagents. The use of protected cyanohydrins as carbanion equivalents has been studied by Stork and by Hunig and has found wide applicability in chemical synthesis. Such species may serve as either acyl anion equivalents or homoenolate anions. ... 

The benzoin condensation has recently been recognized as belonging to the general class of reactions that involve masked acyl anions as intermediates. For example, an aldehyde is converted into an addition product RCH(OX)Y, which renders the C—H acidic. Then under basic conditions, a masked acyl anion (see 1) can be formed and may react with an electrophilic component E. Decomposition of the product RCE(OX)Y should regenerate the carbonyl group with formation of RC(0)E. Intermediates such as (1) are us in the conversion of aldehydes into a-hydroxy ketones, a-diketones and 1,4-dicarbonyl compounds, proving to be a powerful strategy in the development of new synthetic methods. ... 

The C-2-exchange of azolium salts via an ylide mechanism was discussed in Section 24.1.2.1. Thiamin pyrophosphate acts as a coenzyme in several biochemical processes and in these, its mode of action depends on the intermediacy of a 2-deprotonated species (32.2.4). In the laboratory, thiazolium salts (3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride is commercially available) will act as catalysts for the benzoin condensation, and in contrast to cyanide, the classical catalyst, allow such reactions to proceed with alkanals, as opposed to araldehydes the key steps in thiazolium ion catalysis for the synthesis of 2-hydroxy-ketones are shown below and depend on the formation and nucleophilic reactivity of the C-2-ylide. Such catalysis provides acyl-anion equivalents. 

In the traditional benzoin condensation, aromatic and heteroaryl aldehydes are converted to a-hydroxy ketones in the presence of a catalytic amount of cyanide ion. Since the discovery of this reaction in the early 20th century, improvements have made, including the use of quaternary thiazolium salts as the catalyst. This improvement has broadened the scope of this reaction to include aliphatic aldehydes to deliver acyloins. Review Hassner, A. Lokanatha Rai, K. M. In Comprehensive Organic Synthesis, Trost, B. M. Fleming, I. Eds. Pergamon Press Oxford, 1991 Vol. 1, Chapter 2.4 The Benzoin and Related Acyl Anion Equivalent Reactions, pp. 541-577. 

Cyanide also plays a part in the benzoin condensation. The simplest example is the synthesis of benzoin (21) from benzaldehyde. The disconnection and logic are the same as in the synthesis of (4), as the cyanide transforms one molecule of benzaldehyde into the acyl anion equivalent (20). The reaction is successful only for nomenolisable aldehydes. 

A number of methods for the generation of acyl anion equivalents from aldehydes have been developed. Related to the benzoin condensation, aldehyde cyanohydrins, protected as their ether derivatives, are readily transformed into anions by treatment with lithium diisopropylamide (LDA). Reaction with an alkyl halide gives the protected cyanohydrin of a ketone from which the ketone is liberated easily. Reaction with an aldehyde or ketone leads to the formation of an a-hydroxy ketone (1.109). ... 

In early studies of this chemistry we had examined the ability of such thiazolium salts to catalyse the benzoin condensation, a process which also formally involves an acyl anion but which is really of course the anion in which the thiazolium salt has been added to the carbonyl group (Figure 2.10). In this sense the thiazolium anion is very much like cyanide anion, the normal catalyst for simple benzoin condensations. Benzaldehyde would be expected to bind into a j8-cyclodextrin cavity, so we attached a thiazolium salt to a primary carbon of j8-cyclodextrin and examined it as a catalyst. We found that this was not a better catalyst for the benzoin condensation, apparently because there was no room in the j8-cyclodextrin cavity for the binding of two benzaldehyde molecules. However it was clear that at least the reaction intermediate was being formed we got very rapid tritium exchange from the aldehyde by formation of the thiazolium adduct, and as well a very rapid oxidation of para-f-butyl benzaldehyde by ferricyanide ion since it was able to oxidize the reaction intermediate formed when the bound t-butyl benzaldehyde underwent addition of the thiazolium ring. 

The benzoin condensation is an example of a reaction that proceeds via acyl anion equivalent intermediates. Provide mechanisms for the following reactions. (Functional Groups-10)... 

In addition, the use of thiazolium catalyzed processes to prepare conq)ounds which are the result of an acyl anion addition reaction have shown utility in synthetic organic chemistry. The benzoin condensation (21-24) and the Stetter reaction (25-27) represent two of the most powerful exan5>les of these types of transformations (Figure 2.). 

In a series of publications beginning in 1973, Hermann Stetter and coworkers reported that activated olefins could intercept the putative acylanion intermediate of the benzoin reaction. Typical catalysts for the benzoin reaction, sodium cyanide and thiazolylidine carbenes, were found to perform well in this new reaction. Stetter also established that the success of the reaction is due to the reversible nature of the benzoin condensation relative to the irreversible formation of 1,4-dicarbonyl products. As a consequence, benzoins or aldehydes can be used interchangeably as reactants. The reaction has proven to be a highly efficient method for the synthesis of 1,4-dicarbonyl compounds and 4-oxonitriles. A resurgence of interest in acyl anion chemistry has resulted in many new discoveries, including alternative acyl donors, as well as catalysts capable of highly enantioselective intra- and intermolecular Stetter reactions. ... 

The generation and NMR spectroscopic characterization of diverse Breslow intermediates (121), that is, 2,2-diaminoenols, have been reported/or the first time by noixing stoichiometric amounts of the saturated carbene and an aldehyde. The reactivity, as acyl anion equivalents, of the so-generated Breslow intermediates (121) has been further demonstrated in cross-benzoin condensation reactions. 

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