Acyl anions synthetic utility

In 1976, Stetter extended the synthetic utility of the Breslow intermediate (1) as an acyl anion equivalent by showing that aldehydes could be coupled with Michael acceptors to generate 1,4-dicarbonyl compounds [55]. 

The synthetic utility of a-phosphorus- and a-thio-stabilized carbanions is the subject of numerous reviews.21 Notable are additions of phosphonium ylides (237),183 sulfonium ylides (238),l84 ° oxosulfo-nium ylides (239)184 " and sulfoximine ylides (240)184,1 to electron-deficient alkenes which afford nucleophilic cyclopropanation products. In contrast, with a-(phenylthio)-stabilized carbanions, which are not acyl anion equivalents, either nucleophilic cyclopropanation or retention of the hetero substituent occurs, depending on the acceptor and reaction conditions used. For example, carbanion (241) adds to 1,1-... 

The possibilities for assembling carbogenic structures have sharply increased in recent years with the advent of various synthetic strategies for generating the equivalents of carbon electrophiles and nucleophiles which are unavailable in structures containing simple core functional groups such as carbonyl, amino, or hydroxyl. For example, acyl anions (RCO), which for various reasons are not readily available, can be utilized in synthesis in modified or equivalent forms. Several acyl anion... 

The most straightforward method for nucleophilic introduction of acyl and aroyl groups into organic molecules is the use of carbonyl anions, represented by acyl-and aroyllithiums, as nucleophiles. Their synthetic utility, however, has been severely limited for a long time because of difficulties both in their generation and in controlling their reaction courses. A practically useful route to acyl- and aroyllithiums has been developed, based on the efficient lithium-tellurium exchange of tellurol esters [123]. 

In a similar manner, conjugate addition of azlactones possessing isopropyl or isobutyl groups at the C4-position to a series of acyl phosphonates proceeded with y-selectivity and high stereoselectivity under the catalysis of quinine-derived thiourea 19c. The phosphonate moiety of the resulting adducts was readily replaced with various heteronucleophiles such as alcohols and amines in situ under the influence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (Scheme 17) [33]. The synthetic utility of azlactones as an acyl anion equivalent in this y-selective addition... 

The perhydroxyl anion, HO2 , is quite a powerful nucleophile and, as seen later, will attack substrates such as electron-deficient olefins (e.g. a,P-unsaturated ketones) and aldehydes - reactions with some synthetic utility, and also of value in bleaching and product purification, particularly of natural materials. In addition, HO2 can be used to generate more powerful oxidants by mixing with electron-deficient acyl compounds (giving peracids) or with nitriles (Payne system, see section 9.3.3.3). 

The synthetic utility of the elimination reaction is enhanced by its usefulness in preparing a number of compounds difficult or impossible to synthesize by other methods. For example, in the preparation of RMn(CO)s compounds by the reaction of XMn(CO)s with anionic alkylating agents, reduction of XMn(CO)s to Mn2(CO)io lowers the yields (63). The alternative route of reacting the metal carbonyl anion with an acid chloride and then decarbonylating the resulting acyl complex is often more desirable (55, 64). 

Most simple acyl- and hydroperoxides readily add oxygen to any tertiary amine giving amine oxide (RgN+O ). These facile reactions are usually carried out at room temperature in water, alcohol or benzene solvent with dilute solutions (even as low as 3%) of an organic peradd. Hydrogen peroxide and Caro s add are less effective, presumably because of the poorer leaving characteristics of the bisulphate and hydroxide anions. The synthetic utility of the various reagents has been reviewed . 

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.). 

An unusual and useful synthesis of spiro-dihydrofuran-3(2/f)-ones has been discoveredand follows the study of the synthetic utility of methoxyallene as a /S-acyl anion equivalent (Scheme 10). High yields were obtained overall (42% for n = 2 73% for n = 3), and the method has been applied to the synthesis of a new class of 17-spiro steroid derivatives. ... 

Trost has published additional applications of a-lithiocyclopropyl phenyl sulphide, including an approach to spiro-sesquiterpenes, involving geminal alkylation, which utilizes a process that is formally the reversal of dithian-carbonyl addition(also see related studies by Marshall Synthetic applications of the highly nucleophilic methoxy-phenylthio-methyl-lithium PhSCH(Li)OMe and of the acyl anion equivalent methylthioacetic acid dianion RSCHCLOCOgLi (R = Me or Ph ) have also been described, as have synthetic procedures based on anions of a-alkylthio- or a-phenylthio-ketones and methylthiomethyl dithiocarbamates. ... 

Negatively charged carbonyl species, which are referred to as carbonyl anions (e.g. acyl- and aroyllithium derivatives), represent one of the more reactive organic intermediates that heretofore has rarely been utilized in practical synthetic reactions [1]. The carbonyl anion is a strong nucleophile, and at the same time it is an electrophile since it has a carbonyl function which is electrophilic in nature. Therefore, reactions involving a carbonyl anion are not straightforward, and usually a complex mixture is obtained from a reaction. 

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