Pyridine fused-polycyclic

Mirtazapine 105, a polycyclic pyridine derivative containing a pyridine ring fused with an azepine ring system, is an antidepressant <2006W02006/008302>. The piperidine derivatives paroxetine 106, alnespirone 107, and Azaloxan... 

Sml2-H20-amine mediated diastereoselective intramolecular couplings were reported for the synthesis of dihydrobenzofuran, and a radical mechanism was proposed to account for this reaction <03OBC2423>. A similar approach for the synthesis of pyridine-fused polycyclic amines was also developed by use of AlBN/BUjSnH as a reducing system <03TL2995>. 

To carry out MCRs of aminoazoles with aldehydes and cyclic CH-acids, the methods of green chemistry were also applied. For example, treatments of 3-methylisoxazol-5-amine and aromatic aldehydes with 1,3-cyclohexanedione, dimedone, 1,3-indanedione, or titronic acid were proceeded in water under micro-wave irradiation at 120°C [100] (Scheme 31). As a result, clean, efficient, and convenient procedures for the generation of polycyclic-fused isoxazolo[5,4-b] pyridines 71 were developed. An interesting fact is that, in the case of 1,3-cyclohexanedione, dihydropyridine s were obtained while in aU other cases only hetero-aromatized derivatives were isolated. No reason for this experimental fact was discussed in the article. 

Polycyclic aromatic heterocycles that contain pyridine rings fused with benzene rings include quinoline and isoquinoline. Quinine, used to treat malaria, is an example of a naturally occurring quinoline. 

Tu and co-workers [74] have synthesized a series of new polycyclic-fused isoxazolo[5,4-h]pyridines 25-29 by a one-pot tandem reaction under microwave... 

Diazafulvene 424 reacts with alkenylcarbenes 425 through a formal [64-3] heterocyclization in a regio- and stereoselective manner to afford dihydroimidazo[l,2- ]pyridines 426. When enyne carbenes are treated with diazafulvene 424, consecutive and diastereoselective [64-2]/cyclopentannulation cyclization reactions take place affording new polycyclic complex systems 429 that can be appropriately demetallated to the corresponding imidazole-based fused systems. Finally, enyne carbenes undergo consecutive [64-2]/[54-l] cyclization reactions with diazafulvene 424 and rt-butyl-NC to yield tetracyclic adducts 432 (Scheme 102) <2006CEJ3201>. 

Several approaches have been followed for the generation of optically active heteroarenes by homogeneous asymmetric hydrogenation. One approach involves direct asymmetric hydrogenation of the unactivated heteroarene. This approach has been most successful for heteroarenes that are polycyclic, like quinolines, isoquinolines, or quinoxa-lines (benzopyrazines). Less success has been achieved on the direct asymmetric hydrogenation of pyridines. To address this limitation, the hydrogenation of modified pyridines has been conducted. In one set of examples, pyridines and related benzo-fused heteroarenes were modified at tfie nitrogen by acylation or the installation of another auxiliary to make the pyridine more electron poor and to dock the catalyst. In a second set of examples, a chiral auxiliary was placed on the pyridine, and the product was formed diastereoselectively by an achiral catalyst. 

The pyridine ring can be fused with benzene rings to produce polycyclic aromatic heterocycles. The most important examples are quinoline and isoquinoline, analogs of naphthalene (Sec. 4.13) but with N in place of CH at C-1 or C-2. 

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