Lithium compounds deprotonation with

Alkylbenzothiazoles, like 2-alkylthiazoles, are CH-acidic. They are deprotonated by -butyl-lithium in THF at -78°C. The lithium compounds react with aldehydes or ketones giving alcohols [102], e.g. ... 

A similar situation is given in the meso-dicarbamate 192 [see Eq. (61)] [120]. The pro-S proton at the pro-R branch exhibits the highest reactivity in the (-)-sparteine-mediated deprotonation to form the lithium compound 193 with a small amount of the diastereomer 195. By applying prolonged reaction times (4-5 h), it is found that 195 is decomposed more rapidly than 193, leading to a further enrichment. Trapping of the reaction mixture by different electrophiles leads to essentially enantiomerically and diastereomerically pure products 194a-c. Allylation and benzylation result in lower diastereomeric ratios, probably due to SET mechanisms in the substitution step. 

Kyba and eoworkers prepared the similar, but not identical compound, 26, using quite a different approach. In this synthesis, pentaphenylcyclopentaphosphine (22) is converted into benzotriphosphole (23) by reduction with potassium metal in THF, followed by treatment with o "t/20-dichlorobenzene. Lithium aluminum hydride reduction of 23 affords l,2-i>/s(phenylphosphino)benzene, 24. The secondary phosphine may be deprotonated with n-butyllithium and alkylated with 3-chlorobromopropane. The twoarmed bis-phosphine (25) which results may be treated with the dianion of 24 at high dilution to yield macrocycle 26. The overall yield of 26 is about 4%. The synthetic approach is illustrated in Eq. (6.16), below. 

Treatment of selenoacetals 24 with butyllithium at 78 °C leads to the chiral a-seleno lithium compounds 25. Selenoacetals are stable compounds and can be readily prepared by selenoacetal-ization of the corresponding aldehydes25,26. In contrast to the corresponding dithioacetals, no competing deprotonation occurs on treatment with butyllithium, even with selenoacetals derived from aromatic aldehydes. 

In spite of the fact that the only a-protons with respect to the carbonyl group in the tricyclic y-keto esters 231 are at bridgehead positions and thus no real enolates can be formed [118], compounds 231 with R = OR could easily and selectively be deprotonated at C-7, and the resulting lithium derivative then substituted with various electrophiles (Scheme 66). 

Another type of sp -hybridized S-oxido functionahzed organolithium compounds has been easily prepared from chloroacetic acid (149). After a double deprotonation with lithium diisopropylamide in THF at —78°C, a DTBB catalyzed (5%) hthiation in the presence of different carbonyl compounds as electrophiles at the same temperature followed by final hydrolysis afforded the expected S-hydroxy acids 151. The corresponding intermediate 150 was probably involved in the process (Scheme 54)" . 

Lithium homoenolates derived from carboxylic acids were generated from the corresponding /3-chloro acids by means of an arene-catalyzed lithiation. Chloro acids 186 were deprotonated with n-butyllithium and lithiated in situ with lithium and a catalytic amount of DTBB (5%) in the presence of different carbonyl compounds to yield, after hydrolysis, the expected hydroxy acids (187). Since the purification of these products is difficult, they were cyclized without isolation upon treatment with p-toluenesulfonic acid (PTSA) under benzene reflux, into substituted y-lactones 188 (Scheme 64) . 

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). 

A first structural characterization of a cyclobutadiene dianion was performed by Boche and coworkers, who generated the dilithium salt of the 1,2-diphenylbenzocyclobutadiene dianion (143) (by deprotonation with n-butyllithium in the presence of TMEDA) (Figure 17) . Nevertheless, the molecular structure of 143 resembles more the structures of dilithiated alkenes, synthesized by reaction of the corresponding alkynes with metallic lithium. In that class of compounds, carbon-carbon bonds, capped by two lithium centres, are the structural motif (see Section II. E). 

An efficient kinetic resolution was also observed during the (—)-sparteine-mediated deprotonation of the piperidin-2-yhnethyl carbamate rac-112 (equation 25). By treatment of rac-112 with s-BuLi/(—)-sparteine (11), the pro-S proton in (/ )-112 is removed preferentially to form the lithium compound 113, which undergoes intramolecular cyclo-carbolithiation, and the indolizidinyl-benzyllithium intermediate 114 was trapped with several electrophiles. The mismatched combination in the deprotonation of (5 )-112, leading to cp/-113, does not significantly contribute to product formation. Under optimized conditions [0.75 equivalents of s-BuLi, 0.8 equivalents of (—)-sparteine, 22 h at —78°C in diethyl ether] the indolizidine 115 was isolated with 34% yield (based on rac-112), d.r. = 98 2, e.r. = 97 3 optically active (5 )-112 was recovered (46%, 63% ee). 

The breakthrough was achieved by D. A. Evans and coworkers " , who demonstrated that aryldimethylphosphine-borane complexes 195 are easily deprotonated by i-BuLi/(—)-sparteine (11), furnishing efficient enantiotopic selection between the methyl groups (equation 45). The intermediate lithium compound 196 was added to benzophenone (to give alcohols 197) or oxidatively coupled to furnish bisphosphines 198 with high ee. The major amount of the minor diastereomer epi-196 is removed as separable meso- 9. ... 

Beak and coworkers accomplished the asymmetric deprotonation of several Ai-Boc-iV-(3-chloropropyl)arylmethylamines (240) with enantiomeric excesses up to 98 2 (equation 56). The intermediate lithium compound 241 cyclizes to form pyrrolidines 242 in good yields and enantioselectivities. The rapid intramolecular substitution step conserves the originally achieved high kinetic differentiation in the deprotonation step. 

Several chapters deal with the synthesis of and the synthetic applications of organolithium compounds such as orthometallation, arene catalysed lithiation, addition to carbon-carbon double bonds, their reaction with oxiranes, and asymmetric deprotonation with lithium (-)-sparteine. We gratefully acknowledge the contributions of ah the authors of these chapters. 

Lewis acid-mediated addition of (phenylthio)trimethylsilane to acryloyl silane takes place to give l,3-bis(phenylthio)-l-trimethylsilylprop-l-ene (18). This compound may be deprotonated with t-butyl lithium at the /J-position and alkylated to give a range... 

A new method of kinetically controlled generation of the more substituted enolate from an unsymmetrical ketone involves precomplexation of the ketone with aluminium tris(2,6-diphenylphenoxide) (ATPH) at —78°C in toluene, followed by deprotonation with diisopropylamide (LDA) highly regioselective alkylations can then be performed.22 ATPH has also been used, through complexation, as a carbonyl protector of y./)-unsaturated carbonyl substrates during regioselective Michael addition of lithium enolates (including dianions of /i-di carbonyl compounds).23... 

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. 

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