Acyl halides methylenation

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Pyrrole and alkylpyrroles can be acylated by heating with acid anhydrides at temperatures above 100 °C. Pyrrole itself gives a mixture of 2-acetyl- and 2,5-diacetyl-pyrrole on heating with acetic anhydride at 150-200 °C. iV-Acylpyrroles are obtained by reaction of the alkali-metal salts of pyrrole with an acyl halide. AC-Acetylimidazole efficiently acetylates pyrrole on nitrogen (65CI(L)1426). Pyrrole-2-carbaldehyde is acetylated on nitrogen in 80% yield by reaction with acetic anhydride in methylene chloride and in the presence of triethylamine and 4-dimethylaminopyridine (80CB2036). 

Other synthetic routes to benzazepines involving ring expansion of six-membered heterocycles include the action of diazomethane (77CPB321), sulfonium ylides (77H(7)37> or acyl halides (75T1991) on quaternary 3,4-dihydroisoquinolines that of sulfoxonium ylides on quaternary quinolines (74IJC(B)1238) and the zinc-acetic acid reduction of quaternary 1-acyltetrahydroisoquinolines (77BSF893). Photoaddition of acyl- or aryl-nitrenes to the exocyclic alkene bond of 2-methylene-1,2-dihydroquinolines results in ring expansion to... 

Ostrovskii et al. <1996MC24> described an unusual acylation reaction of tetrazole triethylammonium salts 231 bis(5-phenyltetrazol-2-yl)acetone 257 was obtained by interaction of various tetrazole triethylammonium salts 231 with 5-phenyl-2-tetrazolylacetyl chloride 256. The mechanism of the reaction is suggested to include a heterolysis of the iV-acyl intermediate resulting in acyl cation formation followed by transacylation of the methylene group in the second molecule of the acyl halide (Equation 40) <1996MC24>. 

Quantitative conversion of 1-adamantanecarbonyl chloride to 1-adamantanecarbox-aldehyde has been accomplished by reduction of the acyl halide at carbon and mercury in MeCN containing TEAP [227]. Lozano and Barba [228] reduced 2-chloro-2-phenylacetyl chloride at mercury in methylene chloride containing TEACl and obtained derivatives of pyran-2-one and pyran-4-one. In subsequent work [229,230], these authors investigated the reduction of 2-bromo-2,2-diphenylacetyl bromide at graphite in methylene chloride containing TEABr and in the presence of inorganic sulfur compounds in the first study, a new sulfurated heterocyclic product was obtained ... 

In an earlier chapter, we saw how to reduce the carbon chain by one methylene unit using the Hunsdiecker reaction. The opposite of this, namely the extension of the carbon chain by one unit, may be achieved with the Amdt-Eistert synthesis. In the first step, an acyl halide is treated with diazomethane to form the a-diazo ketone. This is then treated with water and silver oxide. The resultant product is the free acid. If an alcohol is used instead of water, then the related ester is formed. Suggest what is the pathway for this reaction. 

For acyl halides or anhydrides which do not afford ketenes in the presence of base (such as perfiuoroacyi halides), however, the a-acylmethylenephosphoranes can be prepared directly in one step from the phosphonium salts by using two equivalents of base by the present procedure (Table I).2 Both tetrahydrofuran and methylene chloride have been used as solvents and in the case of the title compound, tetrahydrofuran provides the best results. Good yields of the phosphoranes are generally obtained when is an electron-withdrawing group such as ester or nitrile. The yields of phosphoranes obtained for the thiomethyl or phenyl cases can be... 

A thiazole ring may also be constructed from a lactam thiocarbonyl and one of the following reagents DMAD [3177], a 2-bromoacrylic acid or its nitrile [20S1, 3509], an aryl isothiocyanate and an alkyne [2706, 2915], a reactive a-methylene ketone such as dimedone [3944], an acyl halide [2433] or a halo ketone which is prepared in situ [2475]. 

The bisacylation of methylene-active compounds mentioned above can be avoided by using acylimidazoles in place of acyl halides (acylimidazoles are obtained from the carboxylic acid and sulfinyldiimidazole) for example, reaction of the magnesium enolate of ethyl hydrogen malonate and an acylimid-azole, with concomitant decarboxylation, gives the corresponding / -oxo ester 430... 

Acyl halides, on the other hand, do not methylenate, but give an enolate (Eq. 11.35) ... 

In the Barbier-Wieland degradation, the alpha-methylene group in an aliphatic carboxylic acid is removed in a sequence of reaction steps, effectively a chainshortening. The inverse procedure is the Amdt-Eistert synthesis, where an acid is converted into acyl halide and reacts with diazomethane to give the highest homolog. 

The reaction of acyl halides with carboxylic acids affords good yields of simple and mixed anhydrides. The use of pyridine or triethylamine helps to remove the hydrogen chloride by-product. However, the preparation of benzoic anhydride from benzoic acid and benzoyl chloride has also been carried out in the absence of trialkylamines by heating under reduced pressure, in the presence of zinc chloride or by refluxing in chlorohydrocarbons such as methylene chloride. 

Alkyl- and arylmercury(II) halides are used for the ketone formation[402]. When active methylene compounds. such as /f-keto esters or malonates are used instead of alcohols, acylated / -keto esters and malonates 546 are produced, For this reaction, dppf is a good ligand[403]. The intramolecular version of the reaction proceeds by trapping the acylpalladium intermediate with eno-late to give five- and six-membered rings smoothly. Formation of 547 by intramolecular trapping with malonate is an example[404]. 

Triflates of aluminum, gallium and boron, which are readily available by the reaction of the corresponding chlorides with triflic acid, are effective Fnedel-Crafis catalysis for alkylation and acylation of aromatic compounds [119, 120] Thus alkylation of toluene with various alkyl halides m the presence of these catalysts proceeds rapidly at room temperature 111 methylene chloride or ni-tromethane Favorable properties of the triflates in comparison with the correspond mg fluorides or chlorides are considerably decreased volatility and higher catalytic activity [120]... 

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