"Site Selective" Formation of Low-Valent Titanium Reagents: An "Instant" Procedure for the Reductive Coupling of Oxo Amides to Indoles

Aromatic acylamido carbonyl compounds are readily cyclized to indole derivatives upon treatment with low-valent titanium reagents of the formal oxidation states 0,+1, and+2. Other strong reducing agents such as SmI 2 and low-valent zirconium, niobium, and tungsten complexes are also capable of effecting such intramolecular alkylidenation reactions of amides. From the preparative point of view these heterocycle synthe- ses are best effected with an active titanium species which is prepared in the presence of the carbonyl compound upon coordination of TiCl n (n=3, 4) to the oxo amide substrate and reduction of this complex with zinc dust («instant» method). This procedure turned out to be as effec- tive as the titanium-graphite-based methodology previously described but is much easier to perform as all hazardous reagents are avoided