Acylpyridinium salt

A study on the effectiveness of various cyclohexyl-based chiral auxiliaries in the asynunetric addition of Grignard reagents to 1-acylpyridinium salts 45 has been published <96TL(37)3807>. 

Porphobilinogen and Studies of Its Biosynthesis, ft. Neier. Synthesis and Cycloaddition Reactions of Iso-Condensed Heteroaromatic Pyrroles, C. K. Sha. Azacyclopentadienyl Metal Compounds Historical Background and Recent Advances, C. Janiak and N. Kuhn. Recent Developments in the Synthesis of Marine Pyridoacridine Alkaloids, A. M. Echavar-ren. Alkaloid Synthesis Using 1-Acylpyridinium Salts as Intermediates, D. L. Comins and S. P. Joseph. Index. S S... 

Allyl and benzyl bromides react with a,/ -unsaturated nitriles in the presence of indium(i) iodide under sonication to produce the corresponding allylated and benzylated imines, involving exclusive addition of the allyl/benzyl group to the nitrile moiety (Equation (63)).273 The reaction of allylindium reagents with methyl cyanoacetates affords the corresponding allylation-enamination products (Equation (64)).27 l-Acyl-l,2-dihydropyridines are prepared by indium-mediated allylation of 1-acylpyridinium salts (Equation (65)).275 Quinoline and isoquinoline activated by... 

Reduction of 1-acylpyridinium salts.1 These salts are reduced regiospecifically in moderate yield to 1-acyl-l, 4-dihydropyridines by a copper hydride prepared from lithium trw-butoxyaluminum (3 equiv.) and CuBr (4.4 equiv.) (equation I). 

Comins reported the regiospecific addition of hydride ion to the 4 position of 1-acylpyridinium salts in moderate yields, but with high selectivity (> 90%). The copper hydride reagent used was prepared in situ from lithium tri-trn-butoxyaluminum hydride and cuprous bromide. l-(Phenoxy-carbonyl)pyridinium chloride (97) gave the 1,4-dihydropyridine 98 exclu-... 

The first asymmetric synthesis of (+)-cannabisativine was achived by D.L. Comins et al. using the addition of metallo enolates to a chiral 1-acylpyridinium salt as one of the key steps.The amide bond was created under the Schotten-Baumann conditions from a bicyclic acid chloride and a 1,4-amino alcohol. 

Kuethe, J. T., Comins, D. L. Addition of Metallo Enolates to Chiral 1-Acylpyridinium Salts Total Synthesis of (+)-Cannabisativine. Ora. Lett. 2000, 2, 855-857. 

The addition of nucleophiles to 1-acylpyridinium salts has surfaced as a powerful method for the synthesis of substituted pyridines. The 1-acylpyridinium salts are formed in situ by adding an acyl chloride to a pyridine in an aprotic solvent such as tetrahydrofuran. The formation of the 1-acylpyridinium salt is very rapid and will occur in the presence of various organometallics without significant competition from the reaction of the nucleophile and the acyl chloride. The addition of ethyl chloroformate to a mixture of pyridine and ethylmagnesium bromide gives 1,2- and 1-4-dihydropyridines 29 and 30 in a ratio of 64/36. Although these dihydropyridine intermediates can be aromatized with hot sulfur to 2- and 4-alkylpyridines, the poor regioselectivity makes this procedure unattractive. 

A recent synthesis of jV-methylconiine (161) has been reported, based on the addition of n-PrMgCl to a chiral 1-acylpyridinium salt [434]. 

Unlike tertiary aliphatic amines, pyridine can be A-acylated even in the absence of complex-forming Lewis acids.615 616 1-Acylpyridinium salts have been studied by Krohnke.503... 

Acylation of amides is naturally much harder to achieve, because of their lower basicity, but it is very greatly facilitated by the presence of pyridine.583 617 618 The reason for this effect is, of course, the intermediate formation of 1-acylpyridinium salts as mentioned above.619 For instance, dibenzamide is formed almost quantitatively from benzoyl chloride and benzamide in pyridine solution even at room temperature, whereas there is no reaction in the absence of pyridine.620 Also, by the action of aromatic acid halides on aliphatic or aromatic amides in the presence of pyridine at temperatures as low as —60° to —70° Thompson617 obtained high yields of triacyl derivatives. 

Two related procedures for the synthesis of the quinolizidine ring system have been reported by Comins et al. which utilize, as the key step, regiospecific attack of a functionalized carbanion at the 2-position of a 4-substituted 1-acylpyridinium salt (Scheme... 

Acylpyridinium salts are of great interest in connection with substituted alkylations (see p. 205), but not for their reactions with Grignard reagents. 

Among the most interesting reactions to be discussed in this Section are those involving an 1-acylpyridinium salt and an enolizable carbonyl compound. The original observation in this connection was made by Glaisen and Haase they found the preparation of acetophenone O-benzoate (see below) by reaction of acetophenone with benzoyl chloride in pyridine to be unsatisfactory, but they isolated a yellow compound, shown by v. Doering and McEwen to have the structure (90 R = R" = Ph, R = H) ... 

In the presence of aluminium chloride, 1-acylpyridinium salts give 4-(/)-dialkylaminophenyl)pyridines with dialkylanilinesi2426 ... 

The first, chiral auxiliary mediated, asymmetric synthesis of (+)-luciduline (160) has been accomplished from readily available materials in 14 steps (10% overall) with a high degree of stereocontrol (94). Key steps include an intramolecular Diels-Alder reaction of a chiral dihydropyridine, a subsequent retro-Mannich ring opening, and a novel cationic reductive cyclization reaction. The enantiopure dihydropyridone 164, prepared from the chiral 1-acylpyridinium salt 161, was converted to the 1,2-dihydro-pyridine 166. Intramolecular Diels-Alder reaction and subsequent reduction leads to 168, which, after retro-Mannich ring opening, is converted into the enecarbamate 171. The... 

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