Carbocyclizations substituents

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

Rudisill and Stille developed a two-step procedure in which 2-bromo-or 2-trifluoromethanesulfonyloxyacetanilides were coupled with tri-n-butyl-stannylacetylenes in the presence of Pd(PPh3)4.[l], Cyclization was then effected with PdCl2(CH3CN)2. The conditions are compatible with a variety of carbocyclic substituents so the procedure can provide 2-substituted indoles with carbocyclic substituents. The reported yield ranges from 40% to 97% for the coupling and from 40% to 82% for cyclization. 

The procedure has been found to be compatible with a variety of carbocyclic substituents. Table 5.1 provides some examples of the reaction. 

Analogues related to K-252a, which contain a carbocyclic substituent, have been synthesized by the reaction of the indolocarbazole unit with r-dibromocyclopentene (Equation 7) <2005OBC2953>. 

The oxidation of heterocyclic compounds functions in the. same way mechanistically as for carbocycles. Substituents at the C = C bond are eliminated during the reaction and the heteroatoms do not seem to have an influence on the mechanism of the reaction. 

The reaction sequence has also be extended to systems having carbocyclic substituents. A similar zirconocene intermediate prepared from N-allyl-2-bromoaniline was used in the early stages of a synthesis of the A-ring structure of the antitumor antibiotic CC-1065. The second pyrrole ring was installed by a Hegedus-type cyclization. <94J0C192>... 

A variety of carbocyclic substituents are compatible with the reaction <84JCS(P1)1333, 90AJC329, 90CPB2939>. 

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