Cyclizations 2- imidazole pyridines

Breslow demonstrated the catalytic effect of having not only a Lewis acid zinc center but also an auxiliary catalytic center held in close, but non-binding, proximity. An imidazole or thiophenol (81) demonstrated increase in effectiveness in cyclization of a phosphate derivative.706,707 Pyridine pendents on this macrocycle gave a stability for zinc in line with the Irving Williams series for two pyridine and three pyridine pendents.708 A contrast was noted with other metals (Ni, Cu, Cd, Pb, Fe, and In), all of which increase in stability with three pendent arms as does zinc this was attributed to coordination preferences. 

This alkylation reaction can be applied to intramolecular alkylation affording cyclic products, as shown in Equations (19)-(21). The reaction of 2-vinylpyridines with 1,5- or 1,6-dienes results in the formation of five- or six-membered carbocycles with good efficiency.20,20a,20b In addition to pyridine functionality, oxozole and imidazole rings can be applied to this intramolecular cyclization. When the reaction is conducted in the presence of a monodentate chiral ferrocenylphosphine and [RhCl(coe)2]2, enantiomerically enriched carbocycles are obtained. A similar type of intramolecular cyclization is applied to TV-heterocycles. The microwave irradiation strongly... 

More recently, a new and straightforward one-pot approach was reported by Bu et al. <2003JOC5415>. This reaction involves the cyclocondensation of l,2-dipyridin-2-yl-ethane-l,2-dione 120 and arylaldehydes, in the presence of ammonium acetate. Imidazo[l,5- ]pyridines 121 were obtained in reasonable yields, but competitive formation of imidazoles 122 was observed. The amount of ammonium acetate used in this reaction was also shown to strongly influence the yield of the cyclization (Scheme 38). 

D. la Intramolecular attack by the dialkylamino-group on a neighbouring ester group 254, D.lb Intramolecular nucleophilic attack by imidazole and pyridine 255, D.2 Intramolecular attack by the NHR group 256, D.3 The cyclization of halogeno-amines, etc. 256, D.4 Intramolecular nucleophilic attack on phosphorus 259... 

The imidazolyl-annelated dihydroisoquinoline 78 was accessible from the cyclization of imidazole 79. The outcome of intramolecular substitutions on pyridines turned out to be strongly dependent on the linker between the aromatic cores (Scheme 30). With a c/.v-configured alkene in place, as in 80, the expected benzoisoquinoline 81 was isolated in excellent yield. The frans-configured alkene and the saturated C2-alkane were shown to be less suitable tethers due to the formation of side products. 

Analogous high-yield cyclizations were reported with l-amino-2-nitro-derivatives of pyridines and isoquinolines, which gave the corresponding furoxans [53,54], Anilines oxidized in the presence of indoles afforded Schiff s bases from 2- and/or 3-position in low yield [55], An unexpected rearrangement occurred on treatment of l-phenyl-4-methyl-5-aminopyrimidinone with DIB and catalytic amounts of nickel dichloride, resulting in the formation of an imidazole derivative [56] ... 

The Horner-Wittig reaction of 1-substituted imidazole-2-aldehydes (304) gave intermediates (305) that cyclized to imidazo[l,2-a]pyridin-5-ones (306) (80LA542). 

Intramolecular cyclization of the imidazoles (433) also gave rise to 4,5,6,7-tetrahydro-imidazo[4,5-c]pyridines (434) (75JHC1039). 

Dihydroxyimidazo[4,5-c]pyridine (3-deazaxanthine 436 R = H) and related 2-substituted derivatives (436 R = Cl) and (438) were prepared from the requisite imidazole 4-acetamide-5-carboxylic acid esters (435) and (437) by base-catalyzed cyclization to the imide structure (63JOC304l). 

When primary amines react with a-acylaminoketones the resulting Schiff bases can be cyclized in the presence of phosphoryl chloride, phosphorus pentachloride, or triphenylphosphine and triethylamine in hexachloroethane to give 1-substituted imidazoles (11) (Scheme 2.1.4). The starting a-acyl-aminocarbonyls are readily prepared from a-amino acids by reduction with sodium amalgam [31, 32] or by the Dakin-West reaction [33, 34], which is most conveniently conducted in the presence of 4-(AUV-dimethylamino)pyridine (DMAP) as an acylation catalyst [35 37]. 

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>. 

---