Development of the Ti-Catalyzed Intermolecular Hydroamination of Alkynes

Abstract This account describes the development of Ti-catalyzed intermolecular hydroamination reactions of alkynes, achieved in the author’s laboratories during the last five years. Starting from initial ideas and early results with Cp 2 TiMe 2 as a catalyst precursor, mechanistic studies and applications of Cp 2 TiMe 2 -catalyzed hydroaminations of alkynes for the synthesis of biologically interesting classes of compounds are presented. Particular attention is paid to the identification of improved second generation catalysts such as Cp* 2 TiMe 2 and Ind 2 TiMe 2 . 1 Introduction 2 Initial Ideas 3 Cp 2 TiMe 2 : The First Generation Catalyst 4 Cp* 2 TiMe 2 : The Improved Catalyst 5 Other Titanium Catalysts 6 Ind 2 TiMe 2 : The General Catalyst 7 Hydroamination Reactions Employing Enantiomerically Pure Amines 8 Applications for the Synthesis of Biologically Interesting Compounds 9 Summary and Outlook