Development, Scope, and Applications of Titanium(III)-Catalyzed Cyclizations to Aminated N-Heterocycles

Abstract

The exceptionally mild conditions of a titanium(III)-catalyzed cyclization reaction paired with a convenient acid/base extraction have enabled the straightforward synthesis, isolation, and direct N-functionalization of amino heterocycles such as 3-aminoindoles and -pyrroles. The unprotected heterocycles are ideal building blocks for the installation of aminated indoles and pyrroles into target molecules, but their sensitivity has previously impeded their synthesis by modern catalytic methods. This full paper presents the development and extended scope of the new cyclization methodology. The transformation of the products into fused bis-indoles is also demonstrated along with the discovery of an unusual palladium-catalyzed reductive biphenyl coupling reaction. The titanium(III)-catalyzed cyclization has also been applied to the synthesis of substituted 3-iminoindolines, which are of potential interest for applications in natural product synthesis and exhibit tunable blue-to-green fluorescence properties.

Keywords: homogeneous catalysis; nitrogen heterocycles; reduction; titanium; umpolung.