Directed metalation organolithium compounds

Organolithium compounds can readily be prepared from metallic Li and this is one of the major uses of the metal. Because of the great reactivity both of the reactants and the products, air and moisture must be rigorously excluded by use of an inert atmosphere. Lithium can be reacted directly with alkyl halides in light petroleum, cyclohexane, benzene or ether, the chlorides generally being preferred ... 

This type of metallic exchange is used much less often than 12-32 and 12-33. It is an equilibrium reaction and is useful only if the equilibrium lies in the desired direction. Usually the goal is to prepare a lithium compound that is not prepared easily in other ways, for example, a vinylic or an allylic lithium, most commonly from an organotin substrate. Examples are the preparation of vinyllithium from phenyl-lithium and tetravinyltin and the formation of a-dialkylamino organolithium compounds from the corresponding organotin compounds ... 

Although of limited utility for other types of Grignard reagents, metalation is an important means of preparing a variety of organolithium compounds. The position of lithiation is determined by the relative acidity of the available hydrogens and the directing effect of... 

Alkali metal alkyls, particularly n-butyl lithium, are the most frequently used reagents to form metallated intermediates.246 247 In certain cases (di- and triphenyl-methane, acetylene and 1-alkynes, cyclopentadiene) alkali metals can be directly applied. Grignard reagents are used to form magnesium acetylides and cyclopenta-dienyl complexes.248 Organolithium compounds with a bulky alkoxide, most notably M-BuLi-ferf-BuOK in THF/hexane mixture, known as the Lochmann-Schlosser reagent or LICKOR superbase, are more active and versatile reagents.249-252... 

Other examples of intramolecularly coordinated (by 0 as well as by N groups) organolithium compounds can be found in Setzer and Schleyer (2) and Seebach (4). Two recent reviews are also pertinent. Klumpp (34) deals with 0- and N-assisted lithiation and carbolithiation of nonaromatic compounds, and Snieckus (34a) deals with directed (by amide and carbamate groups) ortho metalation in polysubstituted aromatics. 

Thiophene is sufficiently acidic to be directly metallated upon treatment with n-BuLi (see Figure 4.1). This direct lithiation can also be realized with polystyrene-bound 3-(alkoxymethyl)thiophene [96]. The resulting organolithium compounds react as expected with several electrophiles, such as amides (to yield ketones), alkyl halides, aldehydes, and Me3SiCl [96]. 

One of the largest uses for lithium metal is in the synthesis of organolithium compounds which are of immense utility, generally resembling Grignard reagents, but more reactive.39 They are commonly made by direct interaction of Li with an alkyl or aryl chloride in ether, benzene, or alkanes ethers are slowly attacked, however, by LiR. 

The reaction of butyllithium with cellulose iodotosylate prepared by iodination of cellulose tosylate of high DS (1.65) has bwn studied. General considerations concerning the direction of the reactions proceeding in the system RX + R Li suggest that the interaction between iododeoxycellulose and organolithium compounds may involve the normal Wurtz reaction (7), the reaction of metallization (8), and the... 

Metalation of Weak Acids. The ability to metalate very weak acids is a property which has been used widely for the direct synthesis of organolithium compounds, for new or improved organic syntheses, for polymer grafting, and for telomerizations involving chain transfer by transmetalation. These major topics are covered in seven chapters of this volume, indicating both the scope and utility of this property of N-chelated organoalkali metal compounds. 

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