Aryl compounds azide 1,3-dipolar cycloadditions

The general procedure used for the synthesis of [l,2,3]triazolo[l,2-tf][l,2,4]benzotriazin-l-5(6//)-dione derivatives 506 is shown in Scheme 86. Ionic 1,3-dipolar cycloaddition of the appropriate azide 503 to ethyl phenylacetates gives l-(2-nitrophenyl)-4-aryl-5-oxo[l,2,3]triazoles 504. Catalytic reduction of these compounds affords the corresponding amines 505. Cyclocondenzation of these amines to the final tricyclic compounds 506 is performed using triphosgene in anhydrous tetrahydrofuran solution at room temperature (Scheme 86) <2005JME2936>. 

Molander and Hiersemann (60) reported the preparation of the spirocyclic keto aziridine intermediate 302 in an approach to the total synthesis of (zb)-cephalotax-ine (304) via an intramolecular 1,3-dipolar cycloaddition of an azide with an electron-deficient alkene (Scheme 9.60). The required azide 301 was prepared by coupling the vinyl iodide 299 and the aryl zinc chloride 300 using a Pd(0) catalyst in the presence of fni-2-furylphosphine. Intramolecular 1,3-dipolar cycloaddition of the azido enone 301 in boiling xylene afforded the desired keto aziridine 302 in 76% yield. Hydroxylation of 302 according to Davis s procedure followed by oxidation with Dess-Martin periodinane delivered the compound 303, which was converted to the target molecule (i)-cephalotaxine (304). 

The utility of the Paal-Knorr reaction allows it to stiU remain at the forefront of organic chemistry for the preparation of highly complex substrates and drug-like compounds. The Paal-Knorr reaction was used to synthesize iV-aryl pyrroles 25 with an azide group on the aryl ring. These substrates were subsequently employed in a tandem azide-alkyne 1,3-dipolar cycloaddition reaction to synthesize medicinally important molecules with a diazepine scaffold 27 (14OL560). 

Dipolar cycloaddition of aryl (or benzyl) azides to l,l,l-trifluoro-4-ethoxy-3-butene-2-one proceeded smoothly by heating without solvent. As a result 1-substituted 4-trifluoroacetyl-l/f-l,2,3-triazoles 55 were formed regioselectively in good yield [58]. These compounds were readily hydrated at air exposure. 

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