Mechanism acyloin condensation

There has been considerable discussion of the mechanism of the acyloin condensation. One formulation of the reaction envisages coupling of radicals generated by one-electron transfer. 

Probably the most familiar radical reactions leading to 1,2-D systems are the so called acyloin condensation and the different variants of the "pinacol condensation". Both types of condensation involve an electron-transfer from a metal atom to a carbonyl compound (whether an ester or an aldehyde or a ketone) to give a radical anion which either dimerises directly, if the concentration of the species is very high, or more generally it reacts with the starting neutral carbonyl compound and then a second electron is transferred from the metal to the radical dimer species (for an alternative mechanism of the acyloin condensation, see Bloomfield, 1975 [29]). 

Acetaldehyde itself is transformed by entirely different mechanisms, partly by acyloin condensation, as was found in 1921, and partly by... 

Carboxylic esters react with sodium metal to give a-hydroxy ketones (often referred to as acyloins). The reaction, known as the acyloin condensation, is thought to proceed by the mechanism shown in Figure Si3.13. 

The so-called acyloin condensation consists of the reduction of esters—and the reduction of diesters in particular—with sodium in xylene. The reaction mechanism of this condensation is shown in rows 2-4 of Figure 14.51. Only the first of these intermediates, radical anion C, occurs as an intermediate in the Bouveault-Blanc reduction as well. In xylene, of course, the radical anion C cannot be protonated. As a consequence, it persists until the second ester also has taken up an electron while forming the bis(radical anion) F. The two radical centers of F combine in the next step to give the sodium glycolate G. Compound G, the dianion of a bis(hemiacetal), is converted into the 1,2-diketone J by elimination of two equivalents of sodium alkoxide. This diketone is converted by two successive electron transfer reactions into the enediolate I, which is stable in xylene until it is converted into the enediol H during acidic aqueous workup. This enediol tautomerizes subsequently to furnish the a-hydroxyketone—or... 

Motesharei, K., Myles, D. C. Multistep Synthesis on the Surface of Self-Assembled Thiolate Monolayers on Gold Probing the Mechanism of the Thiazolium-Promoted Acyloin Condensation. J. Am. Chem. Soc. 1997,119, 6674-6675. 

The acyloin condensation converts two esters to an cr-hydroxyketone (an acy-loin), often in an intramolecular fashion. The reaction proceeds by a mechanism very similar to the pinacol coupling, except that after the radical-radical combination step there are two elimination steps and two more electron transfer steps. The intramolecular reaction works well for a wide variety of ring sizes. 

Under the reductive condition, the ester group is reduced to hemiacetal radical by sodium, and the coupling of the radical pairs accompanied with the elimination of alkoxide affords the Qf-dicarbonyl intermediate, which is further reduced by two sodium atoms to ene-diolate. Upon hydrolysis, the ene-diol tautomerizes to acyloin product. A general mechanism for acyloin condensation is displayed below. 

Acetyllactic acid results from an acyloin condensation and loss of carbon dioxide, followed by a very interesting ketol rearrangement, which proceeds in a stereochemically uniform manner. Herein, the hydroxy- and keto-groups are oriented syn-periplanar, so that the methyl group is transferred suprafacially on the (Jle)-side, a mechanism, which is supported by data from NMR spectroscopy on model compounds [260] and by preparative examples. [261, 262] The ketol rearrangement is to some extent related to the benzil-benzilic acid rearrangement. 

Attempted acyloin condensation of A does not take the usual course. Instead, B is formed. Suggest a mechanism. 

Early work on the acyloin condensation (which can also be carried out between separate ester reactants) was effected by Bouveault, L. Locquin, R. Compt. Rend. Seances Acad. Sci., 1903,136,1676, and, in an attempt to establish the mechanism by subsequent investigators, for example, Lynn, X W. English, J. J. Am. Chent Soc., 1951, 75,4284. 

A new and detailed mechanism for the acyloin condensation encompasses many previously inexplicable results 2Uid reactions. Included is the metal-ammonia reduction of dimethyl malonate, for which a series of cyclopropane and cyclopropene epoxide intermediates have been suggested. ... 

Mills, W. H. (1922). LIV.-The cyanine dyes. Part IV. Cyanine dyes of the benzothiazole series.. Chem. Soc. Trans. Vol. 121, pp. 455-466, ISSN. 0368-1645 Mohanazadeh, F. Aghvami, M (2007). Thiazolium Salt Immobilized on Ionic Liquid An Efficient Catalyst and Solvent for Preparation of a-Hydroxyketones. Phosphorus, Sidfitr Silicon Relat. Elem. Vol. 182, No. 10, pp. 2467-2475, ISSN. 1042-6507 Motesharei, K Myles, D. C (1997). Multistep Synthesis on the Surface of Self-Assembled Thiolate Monolayers on Gold Probing the Mechanism of the Thiazolium-Promoted Acyloin Condensation. /. Am. Chem. Soc. Vol. 119, No. 28, pp. 6674-6S75, ISSN. 0002-7863... 

A second important reductive coupling procedure involves the reduction of esters to a-hydroxy ketones (acyloins). This reaction is usually carried out with sodium metal in an inert solvent. Diesters undergo intramolecular reactions and this is also an important method for preparation of medium and large carbocyclic rings. There has been considerable discussion of the mechanism of the acyloin condensation but the picture may be complicated by the possibility that the reaction is a heterogeneous one, taking place on the surface of the reacting metal. 

Although the catalysis of the dimerization of aldehydes to acyloins by thiazolium ion has been known for some tlrae, the development of procedures using anhydrous solvents which give satisfactory yields of acyloins on a preparative scale was first realized in the submitters laboratories. The mechanism proposed by Breslow - for the thiazolium ion-catalyzed reactions is similar to the Lapworth mechanism for the benzoin condensation with a thiazolium ylide replacing the cyanide ion. Similar mechanisms are involved... 

Acyloins (a-hydroxy ketones) are formed enzymatically by a mechanism similar to the classical benzoin condensation. The enzymes that can catalyze reactions of this type arc thiamine dependent. In this sense, the cofactor thiamine pyrophosphate may be regarded as a natural- equivalent of the cyanide catalyst needed for the umpolung step in benzoin condensations. Thus, a suitable carbonyl compound (a -synthon) reacts with thiamine pyrophosphate to form an enzyme-substrate complex that subsequently cleaves to the corresponding a-carbanion (d1-synthon). The latter adds to a carbonyl group resulting in an a-hydroxy ketone after elimination of thiamine pyrophosphate. Stereoselectivity of the addition step (i.e., addition to the Stand Re-face of the carbonyl group, respectively) is achieved by adjustment of a preferred active center conformation. A detailed discussion of the mechanisms involved in thiamine-dependent enzymes, as well as a comparison of the structural similarities, is found in references 1 -4. 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

There are currently two proposed mechanisms for the acyloin ester condensation reaction. In mechanism A the sodium reacts with the ester in a single electron transfer (SET) process to give a radical anion species, which can dimerize to a dialkoxy dianion. Elimination of two alkoxide anions gives a diketone. Further reduction (electron transfer from the sodium metal to the diketone) leads to a new dianion, which upon acidic work-up yields an enediol that tautomerizes to an acyloin. In mechanism B an epoxide intermediate is proposed. ... 

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