Lithiations, w-butyllithium

Reaction of l,3-bis(methylthio)-2-methoxypropane with 2 moles of lithium diisopropylamide5 (or w-butyllithium) effects (a) the elimination of methanol to form l,3-bis(methylthio)propene and (b) the lithiation of this propene to generate l,3-bis(methylthio)allyllithium in solution. Its conjugate acid, l,3-bis(methylthio)propene, can be regenerated by protonation with methanol, and has also been prepared (a) in 31% yield by reaction of methylthioacetaldehyde with the lithio derivative of diethyl methylthiomethylphosphonate,5 (b) in low yield by acid-catalyzed pyrolysis of l,l-bis(methylthio)-3-methoxypropane,6 and (c) in low yield by acid-catalyzed coupling of vinyl chloride with chloromethyl methyl sulfide.7... 

In order to determine the strnctnres of the intermediate organolithium compounds, 1-phenylpropyne was metalated with 4 equivalents of w-butyllithium in refluxing cyclohexane . One hour later, no absorption due to lithiated phenylpropynes was detected. The IR spectrum showed only a strong peak at 1775 cm due to a trilithioallene, which gradually became much stronger. Apparently, the introduction of the first Li atom is much slower than subsequent lithiations, so no mono- and dilithiated species were observed in the IR spectrum. 

Benzyl thiol 70 was deprotonated using w-butyllithium in THF at room temperature, lithiated with DTBB (5%) at 0°C to give the benzyllithium 71 and then treated with electrophiles at temperatures ranging between —30 and 0°C. Final hydrolysis afforded the expected products 72 (Scheme 29 f. The reaction applied to allyl mercaptan failed, giving an intractable mixture of products. 

Korneev and Kaufmann successfully lithiated 2-bromo-l,l-diphenylethylene (46) by bromide-lithium exchange to form 2-lithio-l,l-diphenylethylene (47). A second lithia-tion could be effected in four hours at room temperature by deprotonation of the aromatic ring with w-butyllithium in the presence of TMEDA (Scheme 17). Like in the synthesis of compound 23, the first lithiation activates the ortho-hydrogen atom of the Z-phenyl substituent to give 1,4-dilithium compound 48. In total, three equivalents of the alkyl-lithium base are required the third equivalent is consumed in the trapping reaction of w-bromobutane with generation of octane. 

Due to the formation of phenyUithium, the reaction of bis(phenyltelluriomethyl)silane 118 with w-butyllithium does not lead to the doubly lithiated compound 117a, but to the bis(butyltelluriomethyl)silane 119 and phenyUithium (Scheme 43) . 

For the hthiation reactions of the closely related compound 123 with w-butyllithium, a significant solvent effect was observed by Maercker and coworkers . While a two-fold lithiation process by tellurium-lithium exchange takes place in hexane, yielding highly pyrophoric 91, only a-deprotonation occurs when the reaction is effected in THF, yielding the monohthiated tellurole 124 (Scheme 45). 

The reaction of 86 with w-butyllithium gave some reaction in the pyridine ring, but resulted mainly in lithiation of the 2-position of the ferrocene.84,85 This lithiated intermediate has proven useful for the synthesis of some 2-substituted (2-pyridyl)ferrocenes.86... 

Halogenoisothiazoles and isothiazoles unsubstituted in the 5-position lithiate readily at —70° with w-butyllithium. These lithium derivatives react normally to give a variety of substituted isothiazoles as indicated in Scheme I (yields shown on arrows). This... 

Oxazoles, imidazoles and thiazoles are lithiated in the 2-position, and pyrazoles and isothiazoles in the 5-position. With isoxazoles, w-butyllithium causes ring-opening. 

Unlike previously known anionic rearrangements these reactions proceed rapidly, even at or below room temperature. Moreover, complete lithiation and reprotonation are unnecessary for the rearrangement of 1 to 2. Treatment of either isomer with a trace of w-butyllithium rapidly converts it to a 1 1 mixture of the two isomers (25). This reaction is therefore a catalytic anionic rearrangement. Such reactions with organic migrating groups are still unknown. 

Thiophene-2-carboxylic acid lithiates at C-3, via ortho assistance, using butyllithium, but at C-5 using lithium diisopropylamide. The lithiation of 2-chloro-5-methoxythiophene at C-4 and C-3, in a ratio of 2 1, is instructive. 2-and 3-Bromothiophenes undergo lithium-halogen exchange with w-butyllithium, but a-deprotonation with LDA. ... 

Bis(trifluoromethyl)phenyl derivatives with meta substitution of the trifluoromethyl groups can be converted into phosphanes via regioselective lithiation. Thus, Af,fV-dimethyl-3,5-bis(tri-fluoromethyl)aniline (9) can be treated with butyllithium/W,Af,Af. .V -tctramcthylethylene-diamine or with methyllithium alone to yield isomers 10 or 11, respectively. ... 

M -butyllithium added dropwise to a soln. of o-bromo-N-methyl-N-propoxy-aniline in tetrahydrofuran under argon at — 105°, the mixture stirred for 1.5 h, treated dropwise with benzyl bromide, stirring continued for 30 min, and the mixture allowed to warm to room temp, over 1.5 h intermediate (Y 78%), and W-2 Raney Ni (pre-washed to pH 7 with distilled water) in ethanol stirred at room temp, under argon until reaction complete by t.l.c. (ca. 1 h) - o-benzyl-N-methylaniline (Y 86%). The intermediate o-lithiated alkoxylamine thus serves as an o-lithio-N-alkylaniline equivalent. F.e. and electrophiles s. J. Sisko, S.M. Weinreb, Synth. Commun. 18, 1035-41 (1988). 

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