1 -Acyl-2-alkyl-1,2-dihydropyridines

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]. 

Acyl-2-alkyl-2,3-dihydro-4( 1 //)-pyridones A are readily available heterocycles in both racemic and chiral form. l-Acyl-2-alkyl-l,2-dihydropyridines B are much less readily accessible, especially enantiopure, but are much sought after building blocks for alkaloid synthesis. A very efficient (83-96%) and simple procedure has now been developed for the A — B transformation, illustrated as follows treatment of l-allyloxycarbonyl-2-cyclohexyl-2,3-dihydro-4-pyridone with one equivalent of the Vilsmeier reagent in trichloroethylene at room temperature gave l-allyloxycarbonyl-4-chloro-2-cyclohexyl-l,2-dihydropyridine in 92% yield. 

Acyl-2-fluoro-l,4-dihydropyridines 149, easily synthesized by alkylation of 2-fluoropyridinium salts, undergo hydrolysis to form dihydro-2-pyridones 150 in which only the more stable 3,4-/ra t-isomer is formed. 1,4-Dihydropyridines 149 can also be oxidized with DDQ to form 2-pyridones 151 (Scheme 40) <2002JOC7465, 2000CC2459>. 

Eisner and Sadeghi described the isomerization of dihydropyridine with RhClj-PhjP complex in benzene. Isomerization of l-alkyl-4-acyl-1,2,5,6-tetra-hydropyridines into l-alkyl-4-acyl-l,4,5,6-tetrahydropyridines has been observed. Pd/C-catalysed rearrangement of iV-acyl-l,2,3,6-tetrahydropyridines to N-acylenamines is described . Besselievre, Beugelmans and Husson reported the photochemical isomerization of cyclic allylaminc 79 to enamine 80. An equilibrium favouring 81 over 82 by 93 7 was established by treating 81 with t-BuOK-DMSO at 90°C. 

Chiral I-acyl-2-alkyl-l,2-dihydropyridines.1 The useful 1,2-dihydropyridines can be prepared by reaction of Grignard reagents with the chloroformate 1 derived from reaction of (—)-8-phenylmenthol with 4-methoxy-3-(triisopropylsilyl)pyridinc. The bulky group at C, is essential for high diastcreosclectivity in this reaction, and the C4-mcthoxy group facilitates removal of the chiral auxiliary. Reaction of Grignard reagents with 1... 

Reaction of W-acyl-2-phenyl-l. 2-dihydropyridines with maleimides proceeds with endo-maleimlde anf/-phenyl stereochemistry,351 contrary to an earlier report. Pyrroles lacking electron-withdrawing substituents at N fail to give [4+2J adducts with DMAD even at high pressure 36 5-pivaloyl-2H-isoindole is a stable crystalline material which nevertheless readily forms Diels-Alder adducts with N-alkyl and W-aryl maleimides.37 The 1 3 adduct (27) is among the products from reaction of DMAD with 3-ethoxy- 1-methylisoindole.36... 

There are two other classes of dienyl lactams that have been used synthetically, A -alkyl-2-pyridones (160) and Al-acyl-l,2-dihydropyridines (161). Pyridones tend to be relatively unreactive, requiring high temperatures and often giving low yields of the cycloadduct.Al-Acyl pyrrole derivatives also function as diene partners in the Diels-Alder reaction. 

The formation of N-acylpyridinium ions from acyl chlorides and pyridines is effectively promoted by (la) and i-Pr3SiOTf. The N-acylpyridinium ions are usable for the synthesis of dihydropyridines and their derivatives by alkylation with Grignard reagents [128]. This reaction sequence has been applied to asymmetric alkylation of pyridines using a chiral acyl chloride [129]. 

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