Heterocyclic synthesis six-membered rings

Phosphorus heterocyclic compounds, 1, 493-538 five-membered ring systems, 1, 513-523 nomenclature, 1, 496 six-membered ring systems, 1, 497-513 Photoaromatization oxirenes from, 7, 125-126 Photobleaching chromenes in, 3, 880 Photochemical reactions heterocyclic compound synthesis from, 5, 159 reviews, 1, 56 heterocyclic compounds reviews, 1, 71, 72... 

Ring transformations heterocyclic compounds reviews, 1, 70 Ring-chain tautomerism polyheteroatom six-membered rings, 3, 1056 Ripariochromene A synthesis, 3, 751, 755 Robinson-Gabriel synthesis oxazoles, 6, 216... 

Dipolar cycloaddUions. Interest in 1,3-dipolar cycloadditions increased dramatically during the past 20 years, largely because of the pioneering studies of Huisgen [7, 2] The versatility of this class of pericychc reactions in the synthesis of five-membered-ring heterocyclic compounds is comparable with that of the Diels-Alder reaction in the synthesis of six-membered-ring carbocyclic systems (equation 1)... 

Table 2 A comparison between conventional heating and microwave-assisted synthesis in an intramolecular Heck coupling to heterocyclic derivatives of 2-quinolones 20 and 21. Note the high selectivity in (b), where two possibilities exist to fuse a six-membered ring...

Many versatile approaches to the construction of fused heterocyclic systems (6 5 6) with ring junction heteroatoms have been reported. More general reactions which can be used for synthesis of derivatives of several tricyclic systems, and transformations which have potential for use in the preparation of a series of substituted compounds, are discussed in this section. Formation of the five-membered ring is presented first because it is a conceptually simple approach. It should be noted, however, that the addition of a fused six-membered ring to a bicyclic component offers much more versatility in the construction of a (6 5 6) system. Each subsection below starts with intramolecular cyclization of an isolated intermediate product. Reactions which follow are one-pot intermolecular cyclizations. 

Synthesis of the heterocyclic core possessing a fully saturated six-membered ring can be achieved using a catalytic hydrogenation (see Section 11.10.4.5.5). The six-membered ring can also be formed starting from the appropriate... 

Irnidazo[ 1,2-tf ]py ridines were covered in CHEC(1984) <1984CHEC(6)613> along with others imidazoles fused to six-membered rings and they were reviewed together with imidazo[l,5- ]pyridines in CHEC-II(1996) <1996CHEC-II(8)249>. The chemical literature on this heterocycle is very abundant, due to its easy synthesis (most of the preparations use readily available 2-aminopyridines) and to the very broad spectrum of bioactivities displayed by many derivatives. A simple Beilstein search on the fully conjugated heterocycle (free sites everywhere) disclosed ca. 3000 hits for the past decade. Therefore, this chapter cannot be exhaustive in view of space limitations, but will mainly focus on the original synthetic methods that have appeared in the last decade. 

We were interested in applications of the high level of stereocontrol associated with the asymmetric Birch reduction-alkylation to problems in acyclic and heterocyclic synthesis. The pivotal disconnection of the six-membered ring is accomplished by utilization of the Baeyer-Villiger oxidation (Scheme 7). Treatment of cyclohexanones 25a and 25b with MCPBA gave caprolactone amides 26a and 26b with complete regiocon-trol. Acid-catalyzed transacylation gave the butyrolactone carboxylic acid 27 from 26a and the bis-lactone 28 from 26b cyclohexanones 31a and 31b afforded the diastereomeric lactones 29 and 30. ... 

As six-membered heterocycles are present in a number of natural products and biologically important molecules, solid-phase synthesis of these has been reported very often (Fig. 3.9). Solid-phase synthesis for nearly every six-membered ring including one nitrogen atom are known piperidines (272) [376], tetrahydropyridines (273) [377, 378], dihydropyridines (274) [219, 379, 380], pyridines (275) [349, 381-386], (Scheme 3.37), piperidinones (276) [387], dihydropyridones (277-279) [313, 378, 388-390], pyridinones (280-281) [328, 329] and piperidindiones (282) [391] derivatives. In contrast, the synthesis of six-membered rings with one single oxygen is rarely described. Nevertheless, solid-phase synthesis of dihydropyrans (283-284) [392-394] and tetrahydropyrans (285) [335, 336] has been reported. 

The A1-piperideines, in contrast to the A2- and A3-isomers, are usually very reactive toward nucleophilic reagents. Depending upon the nature of the nucleophile, two reaction pathways are possible (equation 48). The nucleophile can add to the inline carbon or the nucleophile can abstract the a-hydrogen. Since both of the resulting anions can undergo further reactions, A1-piperideines have potential for the synthesis of complex six-membered ring heterocycles. 

When the synthesis of a heterocyclic system containing a diazole fused onto l,2,3-triazin-4-one (e.g., imidazo[4,5-i [l,2,3]tnazin-4-one (Section 10.13.9.1.l(i)) and pyrazolo[3,4-rf [l,2,3]triazin-4-one (Section 10.13.9.1.1(ii))) or 1,2,3-triazole fused onto pyrimidin-4(7)-(di)one (e.g., [l,2,3]triazolo[4,5-rf pyrimidin-4(7)-(di)one (Section 10.13.9.1.l(iv))) is required, the synthesis of the six-membered ring is the most reliable method. There are several recent accounts of six-membered annulations onto 1,2,3-triazoles to give [l,2,3]triazolo[4,5-r/ pyrimidines (Section 10.13.9.1.l(iv)), which are valuable alternatives to 1,2,3-triazole annulation using nitrosation techniques <1996CHEC-II(7)489>. 

Synthesis of Four-, Five- and Six-membered Rings from Carbocyclic or Heterocyclic Precursors 540... 

Synthesis of Six-membered Rings from Other Heterocycles 548... 

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