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 Introduction2 Preparation and Physical Properties3 Solution Structures4 Reactivity and Mechanism4.1 Solvent Decomposition4.2 Alkene and Diene Metalation4.3 Arene Metalations4.4 Dehydrohalogenations5 Selectivity and Applications in Synthesis5.1 Picoline Metalations5.2 C–H Metalation5.3 Dehydrohalogenations5.4 Triflate Alkylation5.5 Allyl Ether Isomerizations5.6 Cyclic Allene Synthesis5.7 Epoxide Elimination5.8 Enolization5.9 Orthometalation6 Flow7 Catalysis8 Organosodium Salts and Secondary Applications9 Conclusion

Highly Reactive Hydrocarbon Soluble Alkylsodium Reagents for Benzylic Aroylation of Toluenes using Weinreb Amides

“…A common strategy to increase the solubility and enhance the reactivity of polar organometallic reagents and s‐block metal amides is the use of Lewis donor additives [19] . In this regard, Collum has assessed the constitution of sodium amides NaHMDS (HMDS=1,1,1,3,3,3‐hexamethyldisilazide) and NaDA (DA=diisopropylamide) in several solvents in the presence of a variety of donor additives and investigated their reactivity in organic transformations such as dehydrohalogenation and metalation [12, 20, 21] . Recently we have shown that NaTMP (TMP=2,2′,6,6′‐tetramethylpiperidide) combined with the tridentate donor PMDETA ( N,N,N′,N′′,N′′‐ pentamethyldiethylenetriamine) and B(O i Pr) 3 can promote the regioselective borylation of non‐activated substrates, offering in some cases complementary selectivities to those observed using transition‐metal catalysed protocols [22] .…”

“…[8][9][10] Recent advances in the field have started to address some of these limitations, supporting the vision of a future more sustainable polar organometallic chemistry for functionalising aromatic molecules (Figure 1b). [11][12][13][14] Figure 1. Examples of reactivity of alkyl-sodium reagents in sodiumhalogen exchange and deprotonative sodiation.…”

“…Recent advances in the field have started to address some of these limitations, supporting the vision of a future more sustainable polar organometallic chemistry for functionalising aromatic molecules (Figure 1b). [11–14] …”

Highly Reactive Hydrocarbon Soluble Alkylsodium Reagents for Benzylic Aroylation of Toluenes using Weinreb Amides

“…Recent advances in the field have started to address some of these limitations, supporting the vision of a future more sustainable polar organometallic chemistry for functionalising aromatic molecules (Figure 1b). [11–14] …”

Sodiated Oppolzer enolates: solution structures, mechanism of alkylation, and origin of stereoselectivity

“…The Oppolzer enolates merged our interest in understanding the structure–reactivity-selectivity relationships of alkali metal enolates 2 with efforts to promote the long-overlooked potential of organosodium chemistry. 3 …”