Lithium diisopropylamide is the chemical compound with the formula [(CH₃)₂CH]₂NLi. Generally abbreviated LDA, it is a strong base used in organic chemistry for the deprotonation of weakly acidic compounds. The reagent has been widely accepted because it is soluble in non-polar organic solvents and it is non-pyrophoric. LDA is a non-nucleophilic base.

Preparation and structure

LDA dimer with THF coordinated to Li cations

LDA is commercially available as a solution with polar, aprotic solvents such as THF and ether, though in practice and for small scale use (less than 50 mmol) it is common and more cost effective to prepare LDA in situ.

Kinetic vs thermodynamic bases

The deprotonation of carbon acids can proceed with either kinetic or thermodynamic reaction control. Kinetic controlled deprotonation requires a base that is sterically hindered. For example, in the case of phenylacetone, deprotonation can produce two different enolates. LDA has been shown to deprotonate the methyl group, which is the kinetic course of the deprotonation. A weaker base such as an alkoxide, which reversibly deprotonates the substrate, affords the more thermodynamically stable benzylic enolate. An alternative to the weaker base is to use a strong base which is present at a lower concentration than the ketone. For instance, with a slurry of sodium hydride in THF or dimethylformamide (DMF), the base only reacts at the solution-solid interface. A ketone molecule might be deprotonated at the kinetic site. This enolate may then encounter other ketones and the thermodynamic enolate will form through the exchange of protons, even in an aprotic solvent which does not contain hydronium ions.

LDA can, however, act as a nucleophile under certain conditions. For instance, it can react with tungsten hexacarbonyl as part of the synthesis of a diisopropylaminocarbyne. If given the proper conditions, LDA will act like any other nucleophile and perform condensation reactions. Other even more hindered amide bases are known, for instance the deprotonation of hexamethyldisilazane (Me₃SiNHSiMe₃) forms such a base ([(Me₃SiNSiMe₃]^-).

References

1. ↑
2. ↑

Further reading

• Non-nucleophilic Bases Helsinki University of Technology

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