Acyloin coupling reactions with esters

Attempts to bring about the acyloin coupling reaction with the diester (31) were unsuccessful. The failure can be attributed to the severe nonbonded interactions between the two ester groups in the cisoid conformation required for coupling to occur. 

Acyloin-type reactions of esters provide the simplest route to 1-siloxy-l-alkoxycyclopropane [21,22] Eq. (6). The reaction of commercial 3-halopropionate with sodium (or lithium) in refluxing ether in the presence of Me3SiCl can easily be carried out on a one mole scale [21]. Cyclization of optically pure methyl 3-bromo-2-methylpropionate [23], available in both R and S form, gives a cyclopropane, which is enantiomerically pure at C-2, yet is a 1 1 diastereo-meric mixture with respect to its relative configuration at C-l Eq. (7). Reductive silylation of allyl 3-iodopropionate with zinc/copper couple provides a milder alternative to the alkali metal reduction [24] Eq. (8). 

Another important coupling reaction uses esters as the electron-accepting species and leads to a-hydroxy ketones (acyloin coupling). Sodium, potassium (less frequently) or sodium-potassium alloys are commonly used as electron donors in nonpolar solvents such as toluene or xylene. The first detectable reaction intermediate after the primary reductive step is the enediolate which can be trapped with tri-alkylsilyl chloride. This method is widely used to synthesize highly nucleophilic alkenes and/or protected acyloins (Scheme 12) [50, 51]. 

The bimolecular reductive coupling of carboxylic esters by reaction with metallic sodium in an inert solvent under reflux gives an a-hydroxyketone, which is known as an acyloin. This reaction is favoured when R is an alkyl. With longer alkyl chains, higher boiling solvents can be used. The intramolecular version of this reaction has been used extensively to close rings of different sizes, e.g. paracyclophanes or catenanes. 

Another important reductive coupling is the conversion of esters to a-hydroxyketones (acyloins). This reaction is usually carried out with sodium metal in an inert solvent. 

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. 

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. 

The reductive coupling of carbonyl compounds with active metals (Na, Mg, Al) yields pinacols. An electron transfer from the metal surface to the carbonyl oxygen (ketyl formation), a soft-soft interaction, is undoubtedly involved. The conversion of esters to acyloins (22, 23) on the surface of metallic sodium is well known. Here the enediolate products can be trapped in situ by Me3SiCl (24). The chlorosilane does not interfere with the coupling, yet it effectively removes the alkoxide ions and neutralizes the enediolate ions immediately on formation. The elimination of RO is imperative, for otherwise Claisen or Dieckmann condensations would compete with the normal course of reaction. These complicating processes require a hard base (e.g. RO ) to abstract a proton from the starting esters, whereas the desired coupling is accomplished by a soft base which is the electrons on the metal surface. 

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