Pyridines dihydro-, review

Pyridine-based N-containing ligands have been tested in order to extend the scope of the copper-catalyzed cyclopropanation reaction of olefins. Chelucci et al. [33] have carefully examined and reviewed [34] the efficiency of a number of chiral pyridine derivatives as bidentate Hgands (mainly 2,2 -bipyridines, 2,2 6, 2 -terpyridines, phenanthrolines and aminopyridine) in the copper-catalyzed cyclopropanation of styrene by ethyl diazoacetate. The corresponding copper complexes proved to be only moderately active and enantios-elective (ee up to 32% for a C2-symmetric bipyridine). The same authors prepared other chiral ligands with nitrogen donors such as 2,2 -bipyridines 21, 5,6-dihydro-1,10-phenanthrolines 22, and 1,10-phenanthrolines 23 (see Scheme 14) [35]. 

Galatsis, P. Hantzsch Dihydro-Pyridine Synthesis In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, 304—307. (Review). 

Stanovnik and co-workers (100,101) systematically investigated the cycloaddition reactions of diazoalkanes with unsaturated nitrogen heterocycles, such as azolo-[l,5-fl]pyridines, pyridazin-3(2/7)-ones, and [fo]-fused azolo- and azinopyridazines. The Stanovnik group have studied the further transformations of the products and reviews of this chemistry are available. In a typical example, the reaction of 6-chlorotetrazolo[l,5-/7]pyridazine (37) with 2-diazopropane yields the NH,NH-dihy-dro-pyrazolo[4,3-(i]tetrazolo[l,5-/7]pyridazine 38 (102) (Scheme 8.11). The latter substrate reacts with acetone to produce an azomethine imine 39 that thermally rearranges to give the fused dihydro-1,2-diazepine 40. The azomethine imine obtained with glucose can be trapped with methyl acrylate to furnish the C-nucleoside 41 (103). 

Ab initio and density functional theoretical studies of the 4 + 2-cycloaddition of 2-azabutadiene with formaldehyde predict a concerted reaction that agrees well with experimental evidence.184 The azadiene A-phcnyl-l -aza-2-cyanobuta-l, 3-dicnc reacts with electron-rich, electron-poor, and neutral dipolarophiles under mild thermal conditions.185 5,6-Dihydro-4//-1,2-oxazines have been shown to be useftd as synthon equivalents of 2-cyano-l-azabuta-1,3-dienes.186 The intramolecular Diels-Alder reaction of 1-aza-1,3-butadienes (106) can be activated by a 2-cyano substituent (Scheme 37).187 Stereoselectivity in the hetero-Diels-Alder reactions of heterobutadienes, nitrosoalkenes, and heterodienophiles has been extensively reviewed.188 The azadiene l-(t-butyldimcthylsilyloxy)-l-azabuta-l, 3-diene (107) reacts with halobenzo-quinones, naphthoquinones, and /V-phcnylmalcimidc to yield low to good yields of various pyridine heterocycles (108) (Scheme 38).189 The 4 + 2-cycloaddition of homophthalic anhydride with /V-(cinnarnylidcnc)tritylamine produces the 3,4-adduct whereas with /V-(ci nnamyI i dcnc)bcnzyI idi nc the 1,2-adduct is produced.190... 

The reaction catalysed by alcohol dehydrogenases is a transfer of hydride ion from the alcohol to the 4-position of the pyridinium ring of the coenzyme NAD+ (Scheme 6), [For a review of hydride transfer in model systems, see Watt (1988).] The two hydrogen atoms at the 4-position of the dihydro-pyridine ring of NADH are diastereotopic, and over the years it has become apparent that some alcohol dehydrogenases transfer the pro-/ ... 

The formation of some pyrroles, pyrrolines, pyrrolidines, pyridines, and tetra-hydropyridines were considered above. Next come the pyrazines, a very important group of odorants. Pyrazines have been reviewed periodically by Maga.231-233 Vemin and Parkanyi216 have tabulated 26 pyrazines, as well as 11 6,7-dihydro-(5//)-cyclopentapyrazines and 9 5,6,7,8-tetrahydroquinoxalines from 15 systems. 

The attacks of heterocyclic A -oxides, e.g. of pyridine, quinoline, isoquinoline, phenanthridine, etc., on activated alkynes (RC CR R = R = COOMe R = Ph, R = COOEt R = Ph, R = CN) pose similar problems . An acyclic intermediate has been postulated but is rarely detected. Some of the possibilities are illustrated in equation (126) . If the open intermediate is formed, then the paths to the ylid and the 2-substituted quinoline in equation (126) seem simple enough, but several possible mechanisms can lead to the 3-substituted products . Other workers regard the reaction of the nitrone (or azomethine oxide) with alkyne as simple cycloadditions - which yield 2,3-dihydro-l,2-oxazoles since these are often unstable, only decomposition products may be found (equation 127). The construction of the indolizine skeleton initiated by a similar process has been reviewed (equation 128). ... 

C-Hydroxy-8-azapurines do not exist as such but as equilibrium mixtures (e.g., 8 9) in which the cyclic amide tautomers greatly preponderate over the hydroxy tautomer. This behavior parallels what was found in the pyridine, pyrimidine, and purine series on evidence from ionization constants and the UV spectra of C- and A -methyl derivatives. A formal name for9 is 1,6-dihydro-8-azapurin-6-one but such specification of the hydrogen atom s position is, in the absence of data, risky for example, pyrimidin-4-one is an equilibrium mixture in which tautomers with mobile hydrogen on N-3 and N-1 preponderate in a 5 2 ratio, respectively. Hence the simpler names, such as 8-azapurin-6-one, will be used in this review. 

The use of A/ -heterocychc carbenes (NHC) as catalysts in the preparation of3,4-dihydro-2H-pyran-2-ones (14EJ05631),the copper-catalyzed synthesis of 3-substimted isocoumarins from o-halobenzoic acids and 1,3-diketones (14JOC8507) and the synthesis and reactivity of pyridine-flised 3-substituted 2-amino-4-arylchromenes (14H(89)1557) have been reviewed. 

Early review F. Krohnke, Synthesis 1976, 1-24. Synthetic applications J. N. Chatteijea et al, Indian J. Chem. 15B, 430 (1977) G. R. Newkome etal, J. Org. Chem. 51, 850 (1986) P. Lhotak, A. Kurfiirst, Coll. Czech. Chem. Commun. 57,1937 (1992) T. R. Kelly et al, J. Org. Chem. 62, 2774 (1997). Cf. Chichibabin Pyridine Synthesis Guareschi-Thorpe Condensation Hantzsh (Dihydro)Pyridine Synthesis. 

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