Cycloisomerizations indole derivatives

Cycloisomerization of o-alkynylanUines 114 into multisubstituted N-protected as well as NH-indoles 115 in the presence of various Cu(II) catalysts was extensively investigated by Hiroya et al. (Scheme 9.44) [200, 201). The authors, demonstrated that, in addition to Cu-catalysts, Ti(IV) and Zn(II) salts could also trigger this cyclization to some extent. Further, it was shown that Cu(OTf)2 catalyst displayed good activities in the case of primary aniline derivatives, whereas Cu(OAc)2 was better suited for secondary aniline derivatives. In both cases, moderate to excellent yields of up-to-trisubstituted indoles 115, bearing a variety of labile functional groups, can be synthesized using this procedure. A cascade cydization-intramolecular C3-alkyl-ation leading to C2-C3 fused indoles was also demonstrated. 

A variety of differently fused indoles 155 can be efficiently assembled via the W(0)-catalyzed cycloisomerization of o-alkynylaniline derivatives 154 under photoirradiation conditions. The proposed mechanistic rationale featured a 1,2 Stevens-type rearrangement in the metal-containing ammonium ylide 157, followed by a 1,2-alkyl... 

Furthermore, Yamamoto and coworkers illustrated that o-(alkynyl)phenylisocya-nates 159 could also be efficiently employed in a similar Pt( 11)-catalyzed cycloisomerization reaction, serving as surrogates of the corresponding carbamate derivatives 160, to provide N-(alkoxycarbonyl)indoles 161 in moderate to excellent yields (Scheme 9.60) [219]. It is believed that a dual-role catalysis with the Pt(II) salt first triggered the initial intermolecular nucleophilic addition of alcohol to isocyanate 159, affording the key transient carbamate 160, which, upon a subsequent Pt(II)-catalyzed 5-endo-dig cyclization, generated the desired product 161. 

An example of a rhodium(I)-catalyzed cycloisomerization of nitrogen-tethered indole-alkylidenecyclopropanes 13 was reported allowing for ready access to azepinoindole derivatives 14, which are tetrahydro-P-carboline homologs (13CEJ13668). 

The cycloisomerization of various skeletons via carbenoid intermediates has been achieved under transition metal-catalysis. Bis-nucleophilic propargyl ethers (88), ° as well as indole-based allenols (91), ° have been shown to be appropriate substrates for cycloisomerization under Pt(II)-catalysis, respectively furnishing bis-heterocyclic systems (89) and carbazole derivatives (92). While the formation of bis-heterocycles (89) mainly relies on the reactivity of the a, -unsaturated carbene (90) as key intermediate, the cyclization of (91) to carbazoles (92) has been suggested to proceed via (93) as the key carbene intermediate. Similarly to substrates (91), allenols (94) have been successfully cycloisomerized under Au(I)-catalysis, thus resulting in the formation of... 

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