Diisopropylamine, lithium salt

Lithium diisopropylamide- Diisopropylamine, lithium salt (8) 2-Propanamine, N-(l-methylethyl)-, lithium salt (9) (4111-54-0) Lithium, methyl- (8,9) (917-54-4)... 

Sometimes this equilibrium mixture of enolate and base won t work, usually because the base (hydroxide or alkoxide) reacts with the electrophile faster than the enolate does. In these cases, we need a base that reacts completely to convert the carbonyl compound to its enolate before adding the electrophile. Although sodium hydroxide and alkoxides are not sufficiently basic, powerful bases are available to convert a carbonyl compound completely to its enolate. The most effective and useful base for this purpose is lithium diisopropylamide (LDA), the lithium salt of diisopropylamine. LDA is made by using an alkyllithium reagent to deprotonate diisopropylamine. 

The effect of the diisopropylamine formed upon the deprotonation is again particularly important, since a complete reversal of the selectivity is observed on going from free diisopropylamine to its lithium salt or to hexamethyldisilazane. On the other hand, there is a strong dependence of the stereoselectivity of the proton transfer on both the nature of the cation and the ligands attached to the metal, though lithium iodide present with the cuprate has no noticeable effect. 

Diisopropylamine has a pK of about 36, showing that it is much less acidic than a typical ketone or aldehyde. By virtue of its two isopropyl groups, LDA is a bulky reagent. It does not easily attack a carbon atom or add to a carbonyl group. Thus, it is a powerful base, but not a strong nucleophile. When LDA reacts with a ketone, it abstracts the a proton to form the lithium salt of the enolate. We will see that these lithium enolate salts are very useful in synthesis. 

Lithium dlisopropylamide (LDA) (Section 18.4) (AC3H7)2N Li The lithium salt of diisopropylamine. A strong base used to form lithium etiolates from carbonyl compounds. 

In practice, the strong base lithium diisopropylamide [LiN(i-C3H7)2 abbreviated LDA] is commonly used for making enolate ions. As the lithium salt of the weak acid diisopropylamine, pl a = 36, LDA can readily deprotonate most carbonyl compounds. It is easily prepared by reaction of butyllithium with diisopropylamine and is soluble in organic solvents because of its two alkyl groups. 

Common reagents such as lithium diisopropylamide (LDA see Chapter 11, Problem 5) react with carbonyl compounds to yield lithium enolate salts and diisopropylamine, e.g., for reaction with cyclohexanone. 

The vast utilization of hindered secondary amines like diisopropylamine or dicyclohexylamine in carbanion chemistry is also based on the difference in their behavior toward protons and other electrophiles. Thus quite a number of the methods depend upon the use of the lithium or magnesium salts of these amines for the generation of carbanionic species. These salts are very strong kinetic bases and therefore are able to abstract a proton from a variety of C-H acids. At... 

Anhydrous piperazine refluxed with methyl formate produced I-formylpiperazine (1725), which was reduced with lithium aluminum hydride to 1-methylpiperazine (1703). l-Nitroso-4-phenylpiperazine in tetrahydrofuran with diisopropylamine, methyllithium, and carbon dioxide formed 2-carboxy-l-nitroso-4-phenylpiperazine, which was cleaved by dry hydrogen chloride in benzene to 3-carboxy-l-phenyl-piperazine (1726). Distillation of the calcium salt of rra/is-2,3-dicarboxy-l, 4-di-phenylpiperazine gave 1,4-diphenylpiperazine (1669). Reduction of 1-ethoxy-carbonyl-4-trifluoroacetylpiperazine with borane in tetrahydrofuran formed... 

On a small scale, it is convenient to add the carboxylic acid to two equivalents of LDA10 or other lithium amide, but larger experiments can be performed by addition of an available organolithium reagent to a suspension of a preformed salt containing equivalent or lesser molar amounts of the amine.12,13 Diisopropylamine reacts more rapidly than carboxylate salts with n-butyllithium. When LDA so formed abstracts a proton from the carboxylate-salt, the amine produced can react again with addi-... 

Acidity of Terminai Aikynes (Section 7.4) Treatment of terminal alkynes 25) with a strong base [most commonly NaNHj, NaH, or lithium diisopropylamine (LDA)] gives an acetylide salt. 

The chemistry of preformed enolates emerged in temporal and causal coherence vith the EDA area . Although lithium and magnesium salts of diisopropylamine vere first developed in the nineteen-fifties [40], lithium diisopropylamide (EDA) has been a videly used reagent since 1970, because of its behavior as a soluble, strong, and non-nucleophilic base [14]. EDA and related bases, for example lithium hexamethyldisilazane (LIHMDS) [41], lithium N-isopropylcyclohexylamide (LICA) [42], and lithium 2,2,6,6-... 

Stronger bases, such as amide anion, methylsulfinylcarbanion (the conjugate base of dimethyl sulfoxide), and triphenylmethyl anion, are capable of effecting rapid and essentially complete conversion of a ketone to its enolate. Lithium diisopropylamide, generated by addition of Ai-butyllithium to diisopropylamine, is widely used for this purpose. It is a very strong base, yet is sufficiently bulky so as to be relatively nonnucleophilic—a feature that is important in reducing a number of side reactions. The lithium and sodium salts of hexamethyldisilazane [(CH3)3Si]2NH are easily prepared and handled compounds with properties similar... 

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