o-Styrylnitrene route to 2-substituted indoles. Pyrolysis of o-azidostyrenes

Abstract

The utility of o-azidostyrene derivatives as indole precursors via o-styrylnitrenes has been examined. The cyclization proceeds efficiently for /3-alkyl-and /S-aryl-o-azidostyrenes and is also satisfactory for /3-acyl-o-azidostyrenes. A synthesis of 2-acylindoles involving two steps, base-catalyzed condensation of a methyl ketone with o-azidobenzaldehyde and pyrolysis to the indole, was carried out successfully in five cases with yields from 21 to 73%. These yields are generally superior to yields of 2-acylindoles prepared by the deoxygenation method.An o-styrylnitrene would be expected to cyclize to an indole on the basis of analogy with other cyclizations of aryl azides having adjacent unsaturated substituents.2 The deoxygenation of o-nitrostyrenes to indoles may, indeed, be an example of such a cyclization.3 In view of the efficiency with which azides serve as precursors of nitrenes on thermal or photolytic decomposition,4 5a study of the synthesis and decomposition of the requisite o-azidostyrenes was undertaken.6 Particular attention was focused on 0-acyl-o-azidostyrenes because of the desirability of developing improved methods of synthesis of 2-acylindoles. Some additional studies of the deoxygenation method are also reported for purposes of comparison.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

“…Ortho ‐alkenyl aryl azides also rearrange to indoles upon heating. This reaction, known as the Sundberg cyclization,331, 332 takes place by direct attack at the β‐carbon atom and not after insertion into the CH bond 332. This reaction was recently applied to the synthesis of complex indoles (Scheme ) 333–335.…”

Rh2(II)-Catalyzed Nitro-Group Migration Reactions: Selective Synthesis of 3-Nitroindoles from β-Nitro Styryl Azides

“…In our first report, 7b no alkyl- or aryl group migration was observed for styryl azides with β-hydrogen substituents (entry 1). Our subsequent study revealed that aryl groups migrate in preference to alkyl groups (entry 2).…”

“…3–5 While nitro group migrations have been observed in isolated cases, 6 these transformations have not been harnessed for the regioselective synthesis of nitro-substituted N -heterocycles. Styryl azides are established as useful indole precursors, 7 and our group has previously reported that Rh 2 (II) octanoate catalyzes a phenyl group migration to transform β,β-diphenylstyryl azide into 2,3-diphenylindole. 2b When the styryl azide contains a β-hydrogen, a C–H amination reaction occurs: thermolysis of β-nitro-substituted 1 was reported by Gribble and co-workers to produce 2-nitroindole 2 as the major product (eq 1).…”

“…12a Neither group, however, will migrate in the presence of a β-hydrogen. 7b Consequently, we rank their migratorial aptitude behind hydrogen. While hydrogen migration is preferred over amide migration in 7d , azide 10e revealed that when the β-hydrogen is replaced with a phenyl group, only amide migration is seen.…”

Reaction of aromatic azides with strong acids: formation of fused nitrogen heterocycles and arylamines

“…After the evolution of nitrogen stopped, the excess AlCl 3 was destroyed by 10% NaOH and after purification on silica gel plates, we isolated trans-2-aminostilbene, mp 101-103 °C 13 , (formed by triplet nitrenium ion hydrogen atom abstraction) in 45% yield and only traces of 3. Thermolysis of 1 in ethylene glycol (reflux for 4 h) also furnished the 2-phenyl-1H-indole in 87% yield but in this case the intermediate is a nitrene 12 . Decomposition of 1, either in acidic conditions or by thermolysis, gave 2-phenyl-1H-indole 3 with comparable yields.…”