Structure, Reactivity, and Synthetic Applications of Sodium Diisopropylamide

Abstract The 60-year history of sodium diisopropylamide (NaDA) is described herein. We review various preparations, solvent-dependent stabilities, and solution structures. Synthetic applications of NaDA reported to date are framed by a mechanism-driven approach, emphasizing selectivities when appropriate. We conclude with examples beyond metalation in which NaDA plays a central role and with a few thoughts on where future applications could be focused. 1 Introduction 2 Preparation and Physical Properties 3 Solution Structures 4 Reactivity and Mechanism 4.1 Solvent Decomposition 4.2 Alkene and Diene Metalation 4.3 Arene Metalations 4.4 Dehydrohalogenations 5 Selectivity and Applications in Synthesis 5.1 Picoline Metalations 5.2 C–H Metalation 5.3 Dehydrohalogenations 5.4 Triflate Alkylation 5.5 Allyl Ether Isomerizations 5.6 Cyclic Allene Synthesis 5.7 Epoxide Elimination 5.8 Enolization 5.9 Orthometalation 6 Flow 7 Catalysis 8 Organosodium Salts and Secondary Applications 9 Conclusion