Synthesis 2020; 52(10): 1478-1497
DOI: 10.1055/s-0039-1690846
short review
© Georg Thieme Verlag Stuttgart · New York

Structure, Reactivity, and Synthetic Applications of Sodium Diisopropylamide

Ryan A. Woltornist
,
Yun Ma
,
Russell F. Algera
,
Yuhui Zhou
,
Zirong Zhang
,
David B. Collum
We thank the National Institutes of Health (GM131713) for support.
Further Information

Publication History

Received: 05 February 2020

Accepted: 08 February 2020

Publication Date:
23 March 2020 (online)


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

 
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