Pyridinium salts, 1-acyl

Acylation of 7-ACA with 2-thienylacetylchloride gives the amide cephalothin (43). Displacement of the allylic acetyl group by pyridine affords the corresponding pyridinium salt cephalori-dine (44). Both these compounds constitute useful injectable antibiotics with some activity against bacteria resistant to penicillin by reason of penicillinase production. 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

Both pyridinium salts and pyridine A-oxides are of increased interest as chiral catalysts in organic reactions. Connon and Yamada independently designed and examined pyridinium salts as chiral catalysts in the acylation of secondary alcohols <06OBC2785 06JOC6872>. These two catalysts can be used for kinetic resolution of various sec-alcohols and uf/-diols in good to moderate enantiomeric excess. 

Silylcuprates have been reported to undergo reactions with a number of miscellaneous Michael acceptors [65]. Conjugate addition to 3-carbomethoxy acyl pyri-dinium salts [65a] affords 4-silyl-l,4-dihydropyridines. Oxidation with p-chlorand generates a 4-acyl pyridinium salt that gives the 4-silylnicotinate upon quenching with water, and methyl 4-silyl-2-substituted dihydronicotinates upon quenching with nucleophiles (nucleophilic addition at the 6-position). The stabilized anion formed by conjugate addition to an a, j8-unsaturated sulfone could be trapped intramolecularly by an alkyl chloride [65b]. 

Just as pyridine is a weaker base than piperidine, it is also a poorer nucleophile. Nevertheless, it reacts with electrophiles to form stable pyridinium salts. In the examples shown, primary alkyl halides form N-alkylpyridinium salts, whereas acyl halides and anhydrides react to give N-acylpyridinium salts. 

In l,3,4-oxadiazolo[3,2-a]pyridinium salts (15) an 0/As exchange can be achieved with tris(tri-methylsilyl)arsine in boiling acetonitrile to yield l,2,4-diazaarsolo[l,5-a]pyridines (16) (R = Me, Pr, Bu, Ph) (Equation (4)) <87TLl5li>. In a corresponding way the compound (17) with R = O-TMS is obtained. Methanolysis gives the hydroxy derivative (18) which exists exclusively in this tautomeric form and which can be O-acylated via the sodium salt (Scheme 3) <88TL3387>. 

The intermediacy of an anhydro base (57) was referred to in Scheme 46. Analogous anhydro bases (pyridone methides) can be formed by deprotonation of quaternary salts of 2- and 4-benzylpyridines and the like. The pyridone methides are usually highly reactive and not readily isolable some stable examples are shown in Scheme 49. Pyridine methides are intermediates in the base-catalyzed alkylation and acylation reactions of pyridinium salts at the exocyclic carbon. Compounds of type (60) have been estimated to have 25-30% dipolar character. Protonation of (60) occurs at the 2 - and 3 -positions in the ratio 4 1 respectively (70JCS(C)800). 

Table 15 Synthesis of 1,3-Disubstituted 2-Azaquinolizinium Salts (267) by Reaction of Ammonium Acetate on 2-Acyl-l-acylmethyl-pyridinium Salts (266 Scheme 131)...

At the 2,3-positions reactions of 2-substituted pyridinium salts with acyl anhydrides... 

A novel microwave-mediated three-component coupling of a-acyl bromides, pyridine and internal alkynes was carried out in the absence of a solvent on activated basic alumina to provide a collection of indolizines (Scheme 3.5)7. It was proposed that the reaction proceeded via in situ generation of a dipole from an N-acyl pyridinium salt, followed by a [3+2] cycloaddition reaction. A dedicated laboratory microwave system was... 

The indolizines constitute the core structure of many naturally occurring alkaloids, such as (-)-slaframine, (-)- dendroprimine, indalozin 167B and coniceine. There are a number of different routes to the synthesis of indolizines and they are most commonly synthesised by sequential N-quaternisation, intramolecular cyclocondensation reactions or the cycloaddition reaction of /V-acyl/alkyl pyridinium salts. 

It was found that basic alumina worked well as the basic catalyst for the in situ dipole generation from the AT-acyl pyridinium salt. A three-component mixture of phenacyl bromide (1 mmol), pyridine (1.2 equiv.) and the acetylene (1.2 equiv.) was thoroughly mixed in basic alumina (1 g) and then irradiated for 8 min at 80% power in a domestic microwave. The products were formed in 87-94% yields when running the reaction under solvent-free conditions and in 60-71% yields when using anhydrous toluene as the solvent. 

The reaction of 2-chloro-2-arylnaphthalides 396 with amines, followed by treatment with thionyl chloride and then antimony pentachlo-ride (73KGS1127), or the intramolecular C-acylation of a-chloro-a-(naphthyl-1/isocyanate 397 by the action of antimony pentachloride (84CB3211), leads to N-protonated or N-alkylated 9-aryI-2-oxonaphtho[c[Pg.66]

Fu has demonstrated that acetate anion attack on the silicon center of the silyl ketene acetal, as well as formation of an acyl pyridinium salt, contribute towards the promotion of these reactions [62]. Additionally, silyl ketene imines have also been shown to participate in analogous asymmetric C-acylation reactions to yield chiral quaternary nitriles, and this method was employed as a key step in the synthesis of verapamil [65]. 

---