Lithium organo amides

Recent structural investigations on lithium organo(fluorosilyl)amides have revealed that the lithium cation can form aggregates with internal lithium coordination to fluorine, and mixed aggregates of the amide and LiF. Structural types such as (205), (206), (207) and (208) have been found for these compounds. 

Carbamate 613 under the same conditions also undergoes remote lithiation and a remote anionic Fries rearrangement, and then the product amide 614 proceeds to direct a remote benzylic lithiation, even though it has a free ortho position. Finally, the benzylic organo-lithium 615 cyclizes onto the amide to form 616—all in one pot (Scheme 240) . 

LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2], Because the reactivity of an organo-metallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles. 

Table 13.4 allows for a comparison of the basicities of the strongest lithium-containing bases. The basicities are measured by the heats of deprotonation liberated upon mixing the reference acid isopropanol with these bases. These heats of deprotonation reveal that organo-lithium compounds are even stronger bases than lithium amides. Their basicities decrease from te/7-BuLi via. sec-BuLi and w-BuLi to PhLi. 

Equilibration of Configurationally Labile Organo-lithium Reagents. The equilibration of diastereomeric pairs of alkyllithium-(—)-sparteine complexes and trapping by achiral electrophiles gives enantioenriched products. Examples are a-(A/,JV-diisopropylcarbamoyloxy)benzyllithium in ether, not in THF, l-phenylethyllithium, and the dilithium salt of A/-methyl-3-phenylpropanoic acid amide (eq 2). ... 

Treatment of Z-bis-thioethers RS—CH=CH—SR with alkali amides or organo-lithium result s in a smooth elimination of thiol with formation of metallated ethynyl sulfides M—C=C—SR [203]. If Z-bis(methylthio)ethene and the reactive basic system BuLi TMEDA in THF are allowed to interact at very low temperatures, no elimination occurs, but a precipitate of the lithio derivative is formed. It has a reasonable stability below — 100°C, thus permitting functionalizations... 

Lithium-halogen exchange. The reagent is useful for preparation of organo-lithiums from acetal-containing substrates, dihaloarenes (monofunctionalization), and halopyridines. Dechlorination of /V-(/3-chloroalkyl)amides apparently cannot be achieved with BuLi alone (stops at (V-deprotonation ), and the use of LN is required." Of course the N,C-dithio derivatives may be employed in C-C bond formation (remarkably the coupling with aryl and vinyl halides). Barbier-type reactions have been achieved."... 

Hidai M, Mizobe Y (1999) Activation of the N-N Triple Bond in Molecular Nitrogen Toward its Chemical Transformation into Organo-Nitrogen Compounds. 3 227-241 Hodgson DM, Stent MAH (2003) Overview of Organolithium-Ligand Combinations and Lithium Amides for Enantioselective Processes. 5 1-20... 

Five research groups with expertise in the field summarize recent fascinating developments, including l,4-dUithio-1,3-butadienes and their transmetallated organo-di-metallic compounds, mixed dimers of lithium amide/alkyllithium, gem-diorganometallic compounds, alkali-metal mixed-metal ate compounds, and lithium zincates. 

Unprotected acids, amides or benzylic alcohols can be tolerated as well using a combination of organo-magnesium and -lithium reagents [58]. 

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