Lithium amines

Based on the early racemic synthesis of 4 (cis series), it had already been demonstrated that 2-azetidinone ring closure could be achieved via nucleophilic attack of a lithium amine anion on a (3-ester. Cyclization could be accomplished with other strong bases, but sodium bistrimethylsilylamide was found to effect efficient cyclization without significant racemization at C3. During the search for experimentally convenient bases, it was noted that Noyori (Nakamura et al., 1983) reported that tetrabutylammonium fluoride (TBAF) as well as LiF, KF, and CsF could serve as the base in Aldol reactions. Treatment of 17a or 17b with TBAF trihydrate in THF did not affect cyclization. After much experimentation it was found that addition of A,0-bistrimethylacetamide (BSA) to 19 followed by TBAF addition, effected 2-azetidinone ring closure. Further optimization found that use of catalytic TBAF (< 1%) in methylene chloride afforded near quantitative cyclization. 

The rates for the methylation of cyclopentanone and for the proton abstraction from 2-methylcyclopentanone were significantly increased by a factor of 7500 and 5, respectively, when six equivalents of HMPA were added to the reaction. Using 31P, 7Li and 13C NMR spectroscopy, Suzuki and Noyori found that the tetrasolvated Dy dimer was exclusively generated from the tetrameric (T0,4) and dimeric (D0,4) tetrasolvated lithium amine-free enolate of cyclopentanone (0.16 M in THF, —100 °C, ratio 2/3)275. Kinetic analysis gave a first-order reaction in dimer and HMPA for the reaction with a modulation for free HMPA33, and a first-order reaction in dimer for deprotonation, independent of HMPA. Possible transition state structures for alkylation and proton abstraction are drawn in Scheme 85. 

Lithium/amines, reduction with, 55. 115. 199 Lithium/biphenyl, 285 Long-range effects, i6et seq., 439,... 

Kaiser, E. M. Comparison of methods using lithium/amine and Birch reduction systems. Synthesis 1972, 391-415. 

Benkeser and co-workers found that the reduction of aromatic nitro compounds by the lithium-amine reagent stops rather cleanly at the aromatic amine even though arylamines can be reduced by excess lithium in ethylamine to cycloh exene derivatives. This surprising finding is aecounted for as follows. Reduetion of the nitro group is attended with generation of alkyl amide ions, and as the concentration of these ions increases an equilibrium is established between the arylamine and the... 

Aromatic hydrocarbons can be reduced to cycloalkenes by calcium dissolved in a mixture of methylamine and ethylenediamine. For example, calcium reduction of p-xylene (57) and anthracene (59) gives 1,4-dimethyl-l-cyclohexene (58) or decahydroanthracene (60) in 84% and 85% yield, respectively (Scheme 4.16). Calcium-amine combinations are different from lithium-amine systems in that they have little or no propensity to reduce internal double bonds despite the large excess of calcium employed. A grayish white precipitate, seemingly calcium alkyl amide. 

Sulfide werden durch Lithium/Amin, Alkalimetall/Ammoniak oder Alkalimetallamal-gam zu einem Gemisch aus Thiol und Kohlenwasserstoff reduziert. 

Aromatische Nitroso-Verbindungen werden mit Natrium in Diathylather je nach Sto-chiometrie zu Azoxy-Verbindungen bzw. Hydroxylaminen reduziert2 (Reduktionen mit Alkalimetall/fl. Ammoniak/Methanol oder Lithium/Amin wurden bisher nicht durch-gefiihrt),... 

The successful reduction of fimctional groups thus considerably extends the scope and usefulness of these imique lithium-amine reducing systems. 

Other examples of the chemical alteration of coal to improve the extractability yield include lithium/amine reduction (Given et al., 1959 Given, 1984), sodium/alcohol rednction (Ouchi et al., 1981), and sodinm/potassium/glycol ether reduction (Niemann and Hombach, 1979). But it must be remembered that even though the extractability of the coal is enhanced, the chemistry of these reactions is not well understood and is often subject to speculation leaving the precise reasons for solubility enhancement open to speculation also. Reactions that enhance coal solnbility by depolymerization (Heredy et al., 1965) also suffer from the same unknowns. 

A Comparison of Methods Using Lithium/Amine and Birch... 

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