3- Acylpyridines, synthesis

Dicarbomethoxyacetylene has also been added to the pyrrolidine enamine derivative of acetylacetone, demonstrating a new synthesis of phthalic esters (345). A 3-acylpyridine synthesis was achieved by the addition of an acetylenic aldehyde to the vinylogous amide derived from ammonia and dihydroresorcinol (346). 

Synthesis of acylpyridines, pyridinecarboxylic acids and their derivatives 98KGS1013. 

Transition metal complexes have been used in a number of reactions leading to the direct synthesis of pyridine derivatives from acyclic compounds and from other heterocycles. It is pertinent also to describe two methods that have been employed to prepare difficultly accessible 3-alkyl-, 3-formyl-, and 3-acylpyridines. By elaborating on reported194,195 procedures used in aromatic reactions, it is possible to convert 3-bromopyridines to products containing a 3-oxoalkyl function196 (Scheme 129). A minor problem in this simple catalytic process is caused by the formation in some cases of 2-substituted pyridines but this is minimized by using dimethyl-formamide as the solvent.196... 

A direct synthesis of 1 -hydroxyquinolizinium salts has been reported only recently.20 This involves the base-catalyzed cyclization of quaternary salts derived from a-bromoketones (e.g. phenacyl bromide) and 2-acylpyridines to give 9 in good yield [Eq. 9]. 

A general synthesis of 2-alkyl-3-acylpyridines is achieved from 2-substituted pyridines via a [2,3]-sigmatropic rearrangement of an intermediate a-cyanoamine... 

In 2014, the You group reported a highly efficient synthesis of enantio-merically enriched substituted piperidines by CPA (l )-32b catalyzed cascade hydrogenative dearomatization of substituted pyridines and AFC reaction with pyrroles (Table 6.3). The reaction of 3-benzoylpyridine with a wide range of 2-arylpyrroles proceeded smoothly, and high yields and ee were obtained for 3-acylpyridines bearing either an electron-poor or electron-rich aryl group. 

With well-positioned substituents, the product from the Ortoleva-King reaction may be followed by readily ring closures to yield a variety of heterocycles. Case in point was made by an elegant synthesis of 2-pyridyl-pyrrocoline 22 reported by Krdhnke et al First, picoline salt 21 was prepared from the Ortoleva-King reaction of acylpyridine 20 and picoline. Upon treatment of saturated sodium bicarbonate 21 underwent rapid cyclization to give rise to pyrrocoline 22 in excellent yield. 

CuBr-catalyzed synthesis of multifunctional imidazo[l,5-a]pyridines through direct C(sp )-H amination of 2-acylpyridines with aliphatic amines using O2 as the green oxidant under 80 C was reported by Ye, Zeng, and coworkers (Scheme 8.62). The electron-rich or poor 2-acylpyridines and aliphatic amines are compatible in this transformation, and the desired products could be obtained in moderate to good yield [107]. 

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