Polycyclic Azaheterocycles

In this section the transition metal catalyzed cycloaddition reactions of polyunsaturated aza-macrocycles are considered for the creation of condensed polycyclic structures. The effect of structural construction of the polialkyne- and enediyne-aza-macrocycles were studied with respect to their chain length, effect of substituents in certain positions, and the nature of unsaturation in the [2- -2- -2] cycloaddition reaction. 

The [2-I-2-I-2] cycloaddition reaction is a pathway to construct complex molecules in a single step in an economical procedure. The potential of the transformation within the macrocyclic unit was successful and resulted in the formation of fused tetracyclic macrocycles in high yield. Thermally induced cycloisomerization that could not be initiated by metals also occurs in the case of such macrocycies. 

Even in 1976 Vollhardt and coworkers had synthesized 1,5,9-cyclododecatriyne, which is stable to irradiation, high pressure, and 

In this chapter, we also evaluate the application polyalkyne and enediyne azamacrocyclic systems [177,182,183]. Since the macrocyclic systems include a nitrogen atom between multiple bonds, their [2-1-2- -2] cycloaddition reactions represent a route to the structures with the polycyclic aza-heterocycles. 

Reaction of macrocycle 2.379a with a catalytic amount of Pd(PPh3)4 failed. The cyclization needed 1.1 equivalents of Pd in refluxing in toluene. The 2,5,8-tris[(2,4,6-triisopropylphenyl)sulfonyl]-2,5,8-triazatrindane 2.381a formed in 54% yield (entry 1). 

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The dipolar cycloaddition chemistry of isomiinchnones is a powerful and concise route to polycyclic azaheterocycles, and Padwa has been the pioneer in this effort. Sheehan and Padwa (159) employed the rhodium-catalyzed isomiinchnone generation and subsequent trapping to a synthesis of 2-pyridones and the alkaloid... 

The dipolar cycloaddition chemistry of isomunchnones is a powerful and concise route to polycyclic azaheterocycles, and Padwa has been the pioneer in this effort. Sheehan and Padwa employed the rhodium-catalyzed isomunchnone generation and subsequent trapping to a synthesis of 2-pyridones and the alkaloid ( )-ipalbidine (465) (Fig. 4.144). Thus ot-diazo imide 462 was readily constructed from 2-pyrrolidinone and allowed to react with rhodium acetate in the presence of c/i-l-(phenylsulfonyl)-l-propene to afford 2-pyridone 464 after loss of phenylsul-finic acid. Further manipulation, featuring a Stille coupling, gave ( )-ipalbidine 465. 

Inter- and intra-molecular [3 + 2] photocycloadditions of 1,3-dipolar species generated by elimination of nitrogen from tetrazoles (103) with alkenes (104) have been reported giving pyrazolines (105). Polycyclic azaheterocycles (108) (110) were also synthesized by [3 + 2] tandem photocycloaddition reactions. Intramolecular-proton-transfer mediated photocycloaddition of 3-hydroxyquinolones (111) with alkenes (113) to give [3 + 2] cycloadducts (114). ... 

A general transformation important for the synthesis of polycyclic heterocycles is the Smiles rearrangement of azaheterocycles. In the case of uracils, 6-chloro-5-nitro derivatives react with o-aminothiophenols. By such S - N rearrangements (710R99 73MI1), pyrimido[5,4-6][l,4]ben-zothiazines besides pyrimido[4,3-/>]benzothiazolines are formed (74CPB1265 80T2097) (Scheme 116). 

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