Structure, Reactivity, and Synthetic Applications of Sodium Diisopropylamide

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