Titanocene complexes by N,O-ligands
were rationally designed and
tuned for selective three-component aza-Friedel–Crafts reactions
of indoles, aldehydes, and unmodified aniline. The combination of
Cp2TiCl2 and 8-hydroxyquinoline favored the
synthesis of the mono aza-Friedel–Crafts adducts, whereas Cp2TiCl2 combined with anthranilic acid overwhelmingly
formed bis-indoles. 1H NMR titration experiments, mass
spectroscopy, X-ray crystal structure analyses, and control experiments
showed that the reaction of Cp2TiCl2 with 8-hydroxyquinoline
resulted in a half-sandwich complex [CpTiCl(C9H6NO)2] (I), in which the Lewis acidity was
enhanced via fine-tuning steric and electronic properties of the Ti
(IV) center, facilitating mono aza-Friedel–Crafts reaction
of indoles, aldehydes, and aniline; in contrast, when anthranilic
acid reacted with the same Ti(IV) precursor, a bis-ligand sandwich
complex Cp2Ti[(o-NH2)PhCOO]2 (II) was obtained, in which both Lewis acidity
of titanium and cooperation with amino groups promoted further transformation
of indoles into bis-indole adducts.