Acyloins synthesis

The reason why the acyloin synthesis is especially characteristic of aromatic aldehydes, depends on the circumstance that in the aromatic series the tertiary carbon atom in the ring does not allow of the aldol condensation, a reaction for which conditions are otherwise much more favourable. The simplest example of the acyloin condensation, moreover, was already encountered in the case of formaldehyde (p. 218) glycollic aldehyde is the simplest acyloin. Acyloin compounds are also produced, in the aliphatic series, by the action of sodium or potassium on esters, and hence are also formed as by-products in the acetoacetic ester synthesis (Bouveault, Scheibler). 

BOUVEAULT HANSLEY- PRELOG - STOLL Acyloin synthesis... 

BOUVEAULT Aldehyde synthesis 39 BOUVEAULT - BUNC Reduction 44 BOUVEAULT - HANSLEY - PRELOG - STOLL Acyloin synthesis 44 BOUVEAULT - LOCQUtN Amino ad synthesis 45... 

Acyloin synthesis. In a novel synthesis by Lawesson and Gronwall t-butyl acetoacetate is prepared from diketene and t-butanol and alkylated, and the benzoyl oxy group is introduced in the a-position by reaction of the sodio derivative with dibenzoyl peroxide. Elimination of the /-butyl group and decarboxylation is accomplished by heating the ester at 160° with a catalytic amount of p-toluenesulfonic... 

Corey and Wat17 found that the method of forming cycloolefins from allylic dihalides and nickel carbonyl provides an unusually efficient route for the formation of large rings. Because it leads to cyclic 1,5-dienes, it makes available a variety of cyclic structures not obtainable in a practical way via the acyloin synthesis. Diacetylenic diols (10) were converted by selective reduction into the corresponding cis.cis- and owu,/ra -ethylenic diols followed by reaction with PBr3 to form the diallylic dibromides (12), which were then cyclized with nickel carbonyl. 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

Carbon—Carbon Bond Formation. Asyimnetiic microbial acyloin condensation was discovered in 1921 (78) and utilized in 1934 in the stereospecific synthesis of (32) (79). 

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with A -bromosuccinimide from cyolo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - ... 

Guareschi imides are useful synthetic intermediates. They are formed from a ketone reacting with two equivalents of the cyanoacetic esters and ammonia. This transformation is illustrated in the formation of 4,4-dimethylcyclopentenone 30.The synthesis was initiated with the Guareschi reaction of 3-pentanone 27 with 28 to generate imide 29. This product was hydrolyzed to the diacid and esterified. Cyclization of the diester via acyloin condensation followed by hydrolysis and dehydration afforded the desired target 30. 

Upon heating of a carboxylic ester 1 with sodium in an inert solvent, a condensation reaction can take place to yield a a-hydroxy ketone 2 after hydrolytic workup. " This reaction is called Acyloin condensation, named after the products thus obtained. It works well with alkanoic acid esters. For the synthesis of the corresponding products with aryl substituents (R = aryl), the Benzoin condensation of aromatic aldehydes is usually applied. 

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 ... 

In general, yields of (/ )-acyloins and (2S,3/ )-diols, respectively, are low due to the formation of several byproducts (mainly reduction products of the substrate). Nevertheless, the optically active compounds thus obtained are extremely useful intermediates for the synthesis of many natural products51. 

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 latter part of the synthesis is straightforward, though silicon must again be used to control the acyloin. 

Scheme 9 Synthesis of bis( 1,2-dithiolene) complexes by sulfuration of acyloins or vicinal diketones and complexation in situ...

The two most important natural pentoses, 1 -arabinose and 1 -xylose, occur in nature as polymeric anhydrides, the so-called pentosans, viz. araban, the chief constituent of many vegetable gums (cherry gum, gum arabic, bran gum), and xylan, in wood. From these pentapolyoses there are produced by hydrolysis first the simple pentoses which are then converted by sufficiently strong acids into furfural. This aldehyde is thus also produced as a by-product in the saccharification of wood (cellulose) by dilute acids. Furfural, being a tertiary aldehyde, is very similar to benzaldehyde, and like the latter undergoes the acyloin reaction (furoin) and takes part in the Perkin synthesis. It also resembles benzaldehyde in its reaction with ammonia (p. 215). 

A relatively recent application to natural product synthesis stems from efforts to synthesize a sesquiterpene called 1-sterpurene 7 [17]. This substance is thought to be the causative agent of the so-called silver leaf disease that affects certain species of shrubs and trees. The strategy focuses on three key steps (a) electrochemical cyclization of the bis unsaturated ester 11 to produce the five-membered ring of 10, (b) a Ruhlman-modified acyloin condensation to... 

The effect of phytoreduction of different types of substances is essentially a result of a competition between the added hydrogen acceptor and the natural acceptor, acetaldehyde. When the latter is displaced it can be identified as such or in the form of its products of dismutation or carboligatic synthesis (acyloin formation). 

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