7- Cyano-6-nitroindole

In contrast, reaction of 82 with NaCN in DMF-H2O at reflux results in the formation of 7-cyano-6-nitroindole (201, 15%) and 83 (4%) as isolable products together with tar matter, and, to our surprise, 2- and/or 3-cyano-6-nitroindoles are not detected at all. When the reaction is carried out in DMSO at 150°C, only demethoxylation occurred to give 83 (62%). On the other hand, utilizing KOt-Bu and p-chlorophenoxyacetonitrile (25), the vicarious substitution reaction (87ACR282) of 82 proceeds smoothly to give a 7-cyanomethylated indole (202, 67%) (2001H1151). 

Yang described the Pd-induced cyclization of an aryl bromide onto a pendant cyano group leading to y-carbolines and related compounds [488], Genet studied the use of chiral palladium complexes in the construction of the C-ring of ergot alkaloids, a study that culminated in a synthesis of (-)-chanoclavine I [489-491]. For example, nitroindole 388 is cyclized to 389 in 57% yield and with enantioselectivities of up to 95% using Pd(OAc)2 and (S)-(-)-BINAP. 

Moreover, a VNS was a key step in the first synthesis of pyrrolo[3,2-e]indole -a heterocyclic fragment of the antitumor antibiotic CC 1065. The a-cyano side chain is installed at the C-4 position on V-(benzyloxymethyl)-5-nitroindole 39 in good yield [25]. This intermediate (40) is then reductively cyclized using Pd(C) to produce the new ring system 41 in 69% yield however, the protecting group does not remain intact at 65°C. If this reaction is carried out at 45°C, the benzyloxy-methyl (BOM) group is left intact, and the pyrrolo[3,2-c]indole is isolated in 62%. 

A versatile synthesis of pyrrolo-annelated quinolines has been reported to occur via alkylation of the VNS products, orf/to-nitroaryl-substituted acetonitriles, with a-bromoketones. The obtained ketonitriles can be reduced under mild conditions with tin(ll) chloride in ethyl acetate-ethanol mixture into quinoline-4-carbonitriles [214]. The same reaction sequence has been applied to 5-nitroindol-4-yl- and 4-nitroindol-5-yl-acetonitriles to obtain tricyclic 4-cyano-2-phenyl derivatives of pyrrolo[3,2-/ - and pyrrolo[2,3-/i]-quinolines (Scheme 91) [214]. 

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