Tert-BuLi

The reaction has broad scope 5-, 6-, and 7-membered ring metallated enol ethers participate equally well as do organocuprates derived from MeLi, PhLi, sec-BuLi, tert-BuLi, MejSnLi, and PhMejSiLi among others. The reaction also works with Grignard reagents. Some examples are given in the Table. 

I f n-BuLi is used for the Br/Li exchange in Figure 5.41, the reaction is completed when the lithio-aromatic compound and n-butyl bromide have formed. It is different when this Br/Li exchange is carried out with ierf-BuLi, where tert-BuLi and /erf-butyl bromide necessarily would have to coexist during the reaction. However, tert-BuLi reacts very fast as a base with tert-butyl bromide via an E2 elimination. Therefore, Br/Li exchange reactions with ferf-BuLi can go to completion only when 2 equivalents of the reagent are used. 

Fig. 10.3. The structures of alkyllithium compounds in solution II contact ion pairs, solvent-separated ion pairs or lithium at-complexes. In THF solution sec- and tert-BuLi are present as contact ion pairs in the same way as phenyllithium (A) or (2,6-diisopropylphenyl) lithium (D) are.

The a-hydrogens of enol ethers may be deprotonated with tert-BuLi Alkylation of the resultant vinyl anions followed by acidic hydrolysis provides an efficient route for the preparation of methyl ketones. 

The reaction occurs quite instantaneously at —78 °C with n-BuLi86) or tert-BuLi 35,99 jn tHF, or with /m-BuLi in ether87. The availability of selenocyclo-propyllithiyms in the last solvent is particularly important since, for example, their nucleophilicity towards carbonyl compounds is enhanced under these conditions 871 (vide infra). However in this solvent sec- or tert-BuLi must be used 87) in place of -BuLi in order to obtain quantitative cleavage of the carbon-selenium bond. For example, l,l-bis(methylseleno)cyclopropane is recovered unchanged after addition of n-BuLi in ether at —78 °C or —40 DC. However, l,l-bis(phenylseleno)-cyclopropane is more reactive since, under these conditions, 35% of 1-lithio-l-phenylseleno cyclopropane is produced ". ... 

C. 5-Methyl-2,2 -bipyridine (3). The 4- and 6-methyl-2,2 -bipyridines may also be prepared using the following procedure. A 500-mL, two-necked, round-bottomed flask (Note 2) with a Teflon-coated magnetic stirrer is placed in a dry ice/acetone bath (-78°C), then 80 mL of tetrahydrofuran (THF) (Note 11) and tert-butyllithium (tert-BuLi) (1.75 M in pentane, 52 mL, 91.0 mmol) Note 12) are added to it, followed by dropwise addition of 2-bromopyridine (7.13 g, 4.3 mL, 45.1 mmol) (Note 13). The canary yellow THF solution becomes reddish-brown upon addition of the pyridyl bromide. After the solution is stirred at -78°C for 30 min, anhydrous zinc chloride (ZnCI2) (13.3 g, 97.4 mmol) (Note 14) is added, and the reaction is stirred at 25°C for 2 hr. The 5-methyl-pyridyl triflate (2) (8.95 g, 37.1 mmol), lithium choride (LiCI) (3.18 g, 75.2 mmol) Note... 

Putting two lithium atoms closer together is more difficult and while the 2,6-dilithium derivative 118 can be made, it cannot be made by double ort/m-lithiation of 67 R = Et. Instead it must be made from dibromide 119 and tert-BuLi. 

Shirley and Cheng (20) reported in 1969 that metalation of 1-meth-oxynaphthalene by BuLi produces a mixture of the 2-lithio and the 8-lithio derivatives in an overall yield of 28% as shown by carbonation. When the same reaction conditions are used except that one equivalent of TMEDA is added, a shift in product composition to > 99.3% 2-metala-tion and < 0.3% 8-metalation occurs, and the yield of l-methoxy-2-naphthalenecarboxylic acid increases to 60%. On the other hand, metalation of 1-methoxynaphthalene with tert-BuLi in pentane-cyclohexane solvent gives a product representing 97% 8-metalation and 3% 2-metala-tion. These selective metalations therefore constitute a useful synthetic route to 1,2- and 1,8-disubstituted naphthalene derivatives. 

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