Titanium catalysis for the synthesis of fine chemicals – development and trends

Titanium is the second most abundant transition metal and is already a key player in important industrial processes (e.g. polyethylene). Titanium is an attractive metal to use for catalytic transformations as it is a versatile and inexpensive metal of low-toxicity and of established biocompatibility. However{,} its potential use as a catalyst for the synthesis of fine chemicals{,} pharmaceuticals and agrochemicals is often overlooked due to its oxophilic{,} Lewis acidic character{,} which renders complexes of titanium less functional group tolerant than their late transition metal counterparts. Nevertheless{,} three different fields of research in titanium catalysis have drawn attention in recent years: formal redox catalysis{,} hydroamination and hydroaminoalkylation. For these reactions{,} titanium offers new approaches and alternative pathways/mechanisms that are complementary to late transition metal-based catalysis. This review focuses on advances in fine chemical synthesis by titanium-catalyzed reactions featuring redox transformations and two important hydrofunctionalization reactions{,} hydroamination and hydroaminoalkylation. Starting from the late 90s{,} we provide an overview of historic inspirational contributions{,} both catalytic and stoichiometric{,} and the latest insights in catalyst design efforts{,} mechanistic details and utility of the three different classes of transformations. Insights to enhance catalyst activity as well as catalyst controlled regio- and stereoselectivities are presented. Illustrative examples that highlight substrate scope and the application of titanium catalysis to the synthesis of complex organic small molecules{,} natural products and materials are shown. Finally{,} opportunities and strategies for on-going research and development activities in titanium catalysis are highlighted.