Driver indole synthesis

Tom G. Driver of the University of Illinois, Chicago found (Angew. Chem. Int. Ed. 2008, 47, 5056) that Rh octanoate catalyzed the well-known thermal conversion of an azide such as 28 to the indole 29. Valeriya S. Velezheva of the A. N. Nesmeyanov Institute of Organoelement Compormds uncovered (Tetrahedron Lett. 2008, 49, 7106) an improved protocol for the Nenitzescu s mthesis, combining 30 and 31 to give 32. For an overview of the nine t5 es of indole synthesis, see our upcoming review in Angewanrfie Chemie. 

Jia [11] and Driver [12] both discovered a Ru-catalyzed intramolecular amination of aryl azides to give indoles, carbazoles, and carbolines (Scheme 2, eqnations 1 and 2), including a synthesis of the y-carboline alkaloid dimebolin... 

Safety considerations were a driver to change the supply route in the synthesis of AZD1981 where the Makosza reaction was conducted above the flash point of acetone in the presence of air and the product nitro-indole (1, Scheme 8.2) was found to be thermally unstable. Furthermore, the yield in the first stage was low and variable (24 to 48%) impacting the overall cost and throughput. The AZ team developed a scalable, potential commercial route to AZD1981 by use of a Semmler-Wolff aromatisation of 2 to 3 to prepare the indole in 51% overall yield (Scheme 8.3). ... 

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