Acyl halides with anions

One type of o-aminobenzyl anion synthon is a mixed Cu/Zn reagent which can be prepared from o-toluidines by / i.s-trimethylsilylation on nitrogen, benzylic bromination and reaction with Zn and CuCN[l]. Reaction of these reagents with acyl halides gives 2-substituted indoles. 

The mesomeric anion (157 Scheme 10) reacts readily with electrophilic reagents such as alkyl or acyl halides at N-2, C-4 and the exocyclic oxygen atom. The percentages of the different products formed are controlled by the HSAB principle. The acylium ion (hard) attacks preferentially at oxygen (hard), whilst the softer alkylating agents attack the nitrogen atom. 

Synthesis of Acyl Nitronates The most general approach to the synthesis of acyl nitronates is based on the reactions of anions of the corresponding AN with acyl halides or carboxylic acid anhydrides in the presence of bases. Here, we will not consider a series of studies, where the formation of intermediate O-acyl nitronates was postulated without conclusive proof or by detection of their decomposition products. 

Acyliminophosphoranes are easily accessible from lithiated triphenylimi-nophosphoranes (16), the latter being generated by lithiation of phospho-nium bromides (Scheme 9). The strongly basic iminophosphorane anion reacts either with an acyl halide (17) or a chlorocarbonate (19) to give triphenyl-A-acyliminophosphorane (18) or product (20), respectively (91S382). 

As one of the most reactive groups of carboxylic acid derivatives, acyl halides are very useful substrates for the preparation of the other classes of derivatives. For example, anhydrides may be synthesized by the reaction of carboxylic acid salts with an acyl halide. In this reaction, the carboxylate anion acts as the nucleophile, eventually displacing the halide leaving group. 

Esters also react smoothly with amines, which is a useful reaction if the corresponding acyl halides or anhydrides are not easily available. The reaction proceeds through the anticipated tetrahedral anionic intermediate. There are two possible leaving groups... 

The reduced basicity of phenothiazine nitrogen requires that even acylation proceed via the anion. The amide (34-2) from the methyl thioether (34-1) can be prepared, for example, by sequential reaction with sodium amide and acetic anhydride. Oxidation of that intermediate with peracid proceeds preferentially on the more electron-rich alkyl thioether to give the sulfone this affords the phenothiazine (34-3) on hydrolysis of the amide. Complex side chains are most conveniently incorporated in a stepwise fashion. The first step in the present sequence involves reaction of (34-3) as its anion with l-bromo-3-chloropropane to give (34-4). The use of that halide with alkylate piperidine-4-carboxamide (34-5) affords the antipsychotic agent metopimazine (34-6) [35]. 

Enolate anions of esters, such as ethyl 3-oxobutanoate or diethyl propanedioate, react with aeyl halides or anhydrides to give acylation products. These reactions are carried out best using sodium hydride instead of sodium ethoxide for production of the enol salt, because then no alcohol is liberated to react with the acyl halide or anhydride ... 

The resulting anion undergoes insertion with carbon monoxide or ketone formation with acyl halides in a manner similar to alkylchlorozirconocenes (Section 31-3A) ... 

The second possibly useful reaction in this group is the tetracarbonylcobalt anion-catalyzed conversion of alkyl halides with a base, CO, and conjugated dienes into acylated dienes (24). In this reaction the alkylcobalt intermediate... 

The reactivity of the compounds is rather limited. For example, benzazaphospholes are not attacked by dilute aqueous acids and bases, oxygen, sulfur or alkyl halides. The coordinating abilities, metalation and interaction of the so formed ambi-dent anion with acyl halides is demonstrated in Scheme 3 (4). 

The dithiane anion 1.9 also reacts with acyl halides, ketones and aldehydes to give the corresponding dioxygenated compounds. Schemes 1.4 and 1.5 show the reaction of dithiane anions 1.11 and 1.12 with ketones. The most common example of umpolung reactivity of a carbonyl group is the benzoin condensation (Scheme 1.6). 

Classically, the acylzirconocene chlorides can be converted into aldehydes, carboxyhc acids, esters, and acyl halides. Recently, the usefulness of acylzirconocenes has been extended. In fact, these unmasked acyl anions directly add to aldehydes and imines affording a-hydroxy or a-amino ketones, respectively. The reaction of acylzirconocene chlorides with imines also proceeds under Bronsted acid-catalyzed conditions, even with aqneons acids. ... 

Although a variety of new preparative routes has been developed in recent years (for reviews see refs 1 -10), the transformation of the metal-carbonyl carbon bond of a metal-carbonyl complex into a metal-carbene carbon bond is still the most useful and versatile method for preparing transition-metal carbene complexes. The addition of a carbanion to the carbon atom of a carbonyl ligand yields an anionic acyl complex that subsequently can be reacted with an electrophile to give a neutral carbene complex. Thus, the syntheses of anionic acyl and neutral carbene complexes are closely related, for almost all the carbene complexes considered in this section acyl complexes are precursors, although most have not been isolated and characterized. The syntheses of acyl complexes via CO insertion (for reviews see refs. 11, 12) or by reaction of metal carbonyl anions with acyl halides is outside the scope of this section. 

A variety of bases have been used to effect dehydrohalogenation of halo acids and halo esters. a-Bromo esters or a-bromo acyl halides give a,/3 lefinic acids with alcoholic potassium hydroxide. Yields are poor with the higher-molecular-weigbt a-bromo acids other products are those formed by substitution of the halogen atom by the basic anions. 

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