Acyloins, preparation

ACYLOINS PREPARED BY THIAZOLIUM ION-CATALYZED CONDENSATION OF ALDEHYDES ... 

Acyloins (la) [29,30] and bis-silylated derivatives of their enediols (lb) [31] have been demonstrated to be useful acyl anion equivalents (RCO ) and have been employed in an indirect but facile way for the preparation of ketones (3) (Equation 7.1). The hydroxy ketones (2), which are the key intermediates in this method, have been prepared by the reaction of acyloins (la) with organic halides in the presence of sodium hydroxide in dimethyl sulfoxide [29, 30] according to the Hein s procedure [32] or using sodium hydride in 1,2-dimethoxyethane (DME) (glyme) [33]. They also have been prepared by the alkylation of lithium enedi-olates of acyloins prepared from the corresponding lb and methyllithium [31]. These reactions proceed with C-alkylation however, the reaction conditions employed are quite basic which would limit substrate choice. 

Preparation of Acyloins. When aUphatic esters are allowed to react with metallic sodium, potassium, or sodium—potassium alloy in inert solvents, acyloins (a-hydroxyketones) are formed (45) ... 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

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... 

Butyroin has been prepared by reductive condensation of ethyl butyrate with sodium in xylene, or with sodium in the presence of chloro-trimethylsilane. and by reduction of 4,5-octanedlone with sodium l-benzyl-3-carbamoyl-l,4-dihydropyridine-4-sulfinate in the presence of magnesium chloride or with thiophenol in the presence of iron polyphthalocyanine as electron transfer agent.This acyloin has also been obtained by oxidation of (E)-4-octene with potassium permanganate and by reaction of... 

Acyloins are useful starting materials for the preparation of a wide variety of heterocycles (e.g., oxazoles and imidazoles ) and carbocyclic compounds (e.g., phenols ). Acyloins lead to 1,2-diols by reduction, and to 1,2-diketones by mild oxidation. 

A solution of bismuth trioxide in hot glacial acetic acid provides a specific method for the oxidation of acyloins. " The reaction rate is dependent on the steric accessibility of the ketol system. A 2,3-ketol requires less than one hour for completion but an 11,12-ketol is not yet fully oxidized in thirty hours." The reaction is highly selective as a-keto acids, hydrazines and phenols are not oxidized. In a direct comparison with cupric acetate, this procedure is somewhat superior for the preparation of a 2,3-diketone from a 2-keto-3-hydroxy steroid. ... 

A spectacular application of the acyloin ester condensation was the preparation of catenaries like 11. These were prepared by a statistical synthesis which means that an acyloin reaction of the diester 10 has been carried out in the presence of an excess of a large ring compound such as 9, with the hope that some diester molecules would be threaded through a ring, and would then undergo ring closure to give the catena compound ... 

As expected, the yields of catenanes by this approach are low, which is why improved methods for the preparation of such compounds have been developed. The acyloins are often only intermediate products in a multistep synthesis. For example they can be further transformed into olefins by application of the Corey-Winter fragmentation. 

The Corey-Winter reaction provides a useful method for the preparation of olefins that are not accessible by other routes. For instance it may be used for the synthesis of sterically crowded targets, since the initial attack of phosphorus at the sulfur takes place quite distantly from sterically demanding groups that might be present in the substrate molecule. Moreover the required vicinal diols are easily accessible, e.g. by the carbon-carbon bond forming acyloin ester condensation followed by a reductive step. By such a route the twistene 10 has been synthesized ... 

Of the many enzymes capable of catalyzing the formation of acyloins only transketolases5 (EC 2.2.1.1) and those of the pyruvate decarboxylase complex6 (EC 4.1.1.1) have, as yet, gained considerable importance for preparative purposes. Therefore, applications of both of these enzymes will be discussed here,... 

The acyloin condensation was used in an ingenious manner to prepare the first reported catenane (see p. 113). ° This synthesis of a catenane produced only a small ield and relied on chance for threading the molecules before ring closure. 

The present procedure for ring expansion has also been applied to l,2-bis(trimethylsilyloxy)bicyclo[n.l.0]alkanes, which are prepared by cyclopropanation of l,2-bis(silyloxy)cycloalkenes. The latter are readily available from acyloin condensations in the presence of chlorotrimethylsilane. " This reaction provides a new route to cyclic 1,3-diketones and macrocyclic compounds containing two 1,3-diketone units in the ring. 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

The O-silylated acyloins such as 1920 c and 1927 are useful synthons for preparation of five-membered aromatic heterocycles such as the substituted imidazole 1925, pyrrole 1926, and furan 1928 [119] (Scheme 12.35). 

Another important reductive coupling is the conversion of esters to a-hydroxyketones (acyloin condensation).267 This reaction is usually carried out with sodium metal in an inert solvent. Good results have also been obtained for sodium metal dispersed on solid supports.268 Diesters undergo intramolecular reactions and this is also an important method for the preparation of medium and large carbocyclic rings. 

Bis(trimethylsiloxy)cyclobutene, a very useful building block, is easily prepared by the modified acyloin condensation of diethyl succinate with sodium in xylene in the presence of trimethylsilylehloride 62). 

The preparative importance of the acyloins depends on the fact that they are intermediate products, from which many 1 2-diketones can be obtained. The simplest aromatic member of this group is benzil (anisil and furil are analogous) like its aliphatic prototype diacetyl CH3.CO.CO.CH3 (and like anhydrous glyoxal) it is yellow in colour. Diacetyl is obtained from methyl-ethyl ketone via the monoxime of the former compound (von Pechmann). It is remarkable that diacetyl condenses to p-xyloquinone. (Formulate). 

Preparation and phytochemical reduction of 2,2 -thenoin and 2,2 -thenil have been studied in the authors laboratory (20a). It has been shown that 2,2 -thenoin gives a color reaction similar to that shown by benzoin and other acyloin condensation products in- the presence of alcoholic alkali. The hydroxy ketone may be oxidized by iodine in the presence of sodium methoxide to give the diketone, 2,2 -thenil, in excellent yields. Phytochemical reduction was shown also to be applicable to both compounds. It is significant that thenoin differs from benzoin, since reduction products were not obtained enzymatically from the latter. 

Aqueous solutions of vanadous chloride (vanadium dichloride) are prepared by reduction of vanadium pentoxide with amalgamated zinc in hydrochloric acid [213], Reductions are carried out in solution in tetrahydrofuran at room temperature or under reflux. Vanadiiun dichloride reduces a-halo ketones to ketones [214], a-diketones to acyloins [215], quinones to hydroquinones [215], sulfoxides to sulfides [216] and azides to amines [217] (Procedure 40, p. 215). 

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