Z-Butyllithium

Mixtures of hexamethyldisilazane, /z-butyllithium, and dimethylzinc reacted, Scheme 55, with the formation of a lithium zincate 70. In the solid state, Figure 37, 70 consists of four-membered, -symmetric LiN2Zn rings, which form a polymeric structure through bridging methyl groups from zinc to lithium.126... 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

Wittig reactions are commonly used for the elaboration of side-chains. When l-methylimidazole-5-carbaldehyde is heated with iodomethyltriphenylphosphonium iodide, and the iodoethenyl product is treated with /z-butyllithium in THF, the ultimate product is the highly toxic 5-ethynyl-l-methylimidazole 616 (Scheme 131). 

In the Schollkopf synthesis, a-metalated isocyanides 13 (from isocyanides and /z-butyllithium) react with acid chlorides to give 4,5-disubstituted oxazoles 14 via C-acylation and electrophilic C-O bond formation. 

Azaferrocene is methylated by /z-butyllithium with subsequent treatment with methyl iodide resulting in formation of 25-27 [83JOM(251)C41]. The acetyl-ated complex T] -(3-acetyl-2,4-dimethylpyrrolyl)cyclopentadienyliron was also described [74JOM(77)69]. The structure of 2-methylazaferrocene was studied extensively (69AG150 96JOC7230 97JA1492 97JOC444). 

The reaction of z-butyllithium and carbon dioxide leads to pentanoic acid after hydrolysis. When you examine your product for confirmation that the reaction worked, what distinguishing features would you look for in the IR spectrum and in the proton NMR spectrum ... 

To study the properties of isotactic poly(acrylic acid), it is necessary to prepare an isotactic poly(acrylate ester) first. The common practice is to polymerize isopropyl acrylate in the presence of /z-butyllithium or of phenylmagnesium bromide at -78 "C in toluene [19]. The polymer is then hydrolyzed as completely as possible so as not to disturb the regularity of the conformation, hinder the cryallization of the polymer (if it is capable of crystallizing), alter its solubility, or change the shape of the polymer chains in solution. 

A soln. of 23 g. l-methoxy-l-buten-3-yne in abs. ether allowed to react at -60° under Ng with a soln. of z-butyllithium in hexane, the resulting soln. added dropwise at -60° to a soln. of 33 g. acetic anhydride in abs. ether, stirring continued 0.5 hr. at -60°, and allowed to warm to room temp. 21 g. 6-methoxy-5-hexen-3-yn-2-one. F. e. s. R. Finding, G. Zimmermann, and U. Schmidt, M. 102, 214 (1971). 

N,N-Dimethy1aniline from Nakarai Chemicals was dried over calcium hydride and freshly distilled. Three molar equivalents of N,N-dimethylaniline are used to achieve complete conversion of the n-butyllithium, because In the present particular case free n-butyllithium, if present, causes the isomerization of the (Z)-alkene to the (E)-isomer. 

The synthesis of enantiomerically pure propargylic alcohols is possible using the same methodology 43b. Thus, addition of (—)-[(l-chloro-2-phenylethyl)sulfinyl]-4-methylbenzene (14) to propan-al led to a mixture of the diastereomers 15A/15B (d.r. 44 56) which are easily separated by column chromatography. After thermal elimination of the sulfinyl group the vinyl chlorides 16A/16B were obtained as a mixture of E- and Z-oleftns. Elimination of hydrogen chloride was carried out with three equivalents of butyllithium, leading to enantiomerically pure 1 -phenyl-1-pentyn-3-ol. 

F,)-2-Rutenvlpotassium Typical Procedure13 To a — 78 C mixture of 22.4g (200mmol) of /-BuOK in 150 mL of dry THF under argon arc added 23 mL (225 mmol) of (L )-2-butcnc. 80 mL (200 mmol) of 2.5 M butyllithium in hexane are then added dropwise at a rate such that the internal temperature does not rise above —65 °C. After completion of the addition, the bath temperature is allowed to rise until the internal temperature reaches — 50 C. The solution is maintained at —50 l C for exactly 15 min and then is immediately recooled to — 78 "C. Temperature control is critical since (/7)-2-buteny(potassium is less stable than, and readily isomcrizes to, (Z)-2-butenylpotassium at this temperature15. 

The preparation of (Z)-2-hutenylpotassium from (Z)-2-butene is analogous to that described for the /T-reagent with the following modification upon completion of the butyllithium addition, the mixture is warmed to —20° to —25 r C for 30-45 min before being recooled to —78 C. This ensures near quantitative formation of (Z)-2-butenylpotassium. Temperature control is less critical since (Z)-2-butenylpotassium is highly favored at equilibrium (99 l)15. However, preparative experiments have not been performed in which ( )-2-butene is metalated under conditions that permit complete isomerization of ( )-2-butenyl-potassium to (Z)-2-butenylpotassium. 

Z)-2-Butenylpotassium is generated from 4.5 mL (50 mmol) of (Z)-2-butene, 2.8 g (25 mmol) or /-BuOK. and 10.8 mL (25 mmol) oT 2.3 M butyllithium in THF for 15 min at —45 JC. This solution is cooled to — 78 C and 30 mmol of a 1 M solution of methoxy(diisopinocampheyl)borane in diethyl elher is added dropwise. The mixture is stirred for 30 min at — 78 °C, then is treated with 4mL (33 mmol) of boron trifluoride-diethyl ctherate complex this removes methoxide from the intermediate ate complex. This solution is immediatelv treated with 35 mmol of an afdchyde. Isolated yields of homoallylic alcohols are 63-79%. 

A solution of 2.5 g (45 mmol) of (Z)-2-butene, 40 mmol of butyllithium and 4.5 g (40 mmol) of /-BuOK in 30 mL of THF is kept for 15 h at — 50 °C. The solution is cooled to —75 C and 20 mL (88 mmol) of the 1 1 fluorodimethoxyboranc-dicthyl ether adduct are added, followed 1 h later by 44 mmol of benzaldc-hyde, The mixture is stirred at — 75 C for an additional hour and is then warmed to 25 C over 30 min and diluted with 100 mL of diethyl ether, washed with three 50-mL portions of NaCl and evaporated. The product is chromatographed on silica gel eluting with hexane/diethyl ether 4 1 and is further purified by distillation yield 40% d.r. (synjanti) 96 4. 

To a stirred — 78 C solution of 5.85 mL (62.5 mmol) of 3-methoxy-l-prnpene in 25 mL of THf- are added 43.1 mL (50 mmol) of 1.16 M. vcc-butyllithium in cyclohexane over a 20-25 min period. The mixture is stirred at — 78 °C for an additional 10 min, and diisopinocampheyl(methoxy)borane [50 mmol prepared from (+ )-a-pinene] in 50 mL of THF is added. This mixture is stirred for 1 h, then 8.17 mL (66.5 mmol) of boron trifluoride diethyl etherate complex are added dropwise to give a solution of diisopiuocampheyl[(Z)-3-inethoxy-2-propenyl]borane. Immediately. 2.8 mL (50 mmol) of acetaldehyde are added and the mixture is stirred for 3 h at — 78 rC and then allowed to warm to r.t. All volatile components are removed in vacuo, then the residue is dissolved in pentane. The insoluble fraction is washed with additional pentane. The combined pentane extracts are cooled to 0 JC and treated with 3.0 mL (50 mmol) of ethanolamine. The mixture is stirred for 2 h at 0rC and is then seeded with a crystal of the diisopinocampheylborane-ethanolaminc complex. The resulting crystals arc filtered and washed with cold pentane. The filtrate is carefully distilled yield 5.6 g (57%) d.r. (synjanti) >99 1 (2/ ,37 )-isomer 90% ee bp 119-120 C/745 Torr. 

Much better results are achieved in the addition of butyllithium to oxime ethers 4a, 4b and 4c activated by boron trifluoride-diethyl ether complex (BF3 OEt2) at — 78 °C (above a reaction temperature of — 30 °C complex mixtures of products are obtained) using toluene as the solvent. Furthermore, the stereoselectivity depends on the E/Z ratio of the starting oxime ethers. The reaction appears to be highly stereoselective, with the diastereoselectivity of the... 

Via the Z-enolate an oven dried Schlenk tube equipped with a rubber septum is flushed with argon and charged with 0.66 mL (1.0 mmol) of butyllithium (1.5 N in hexane). The Schlenk tube is cooled to 0°C (icc/salt) and 0.12 g (1.1 mmol) of diisopropylaminc are added slowly by a syringe. This mixture is stirred for 15 min and the rubber septum is replaced by a glass stopper. The hexane and the excess diisopropyl-amine are removed under reduced pressure. After the flask is filled with argon the stopper is replaced with a septum and 0.47 g (4.3 mmol) of HMPA and 2.5 mL of THF are added. This solution is immediately cooled to — 78 °C and 0.14 g (1.1 mmol) of tert-butyl propanoate arc added quickly by syringe. After stirring for... 

Alternatively, organolithium reagents of the type (CH3)3SiCH(Li)Z, where Z is a carbanion-stabilizing substituent, can be prepared by deprotonation of (CH3)3SiCH2Z with -butyllithium. 

In the case of allylpotassium, the metal complex exists as a symmetric n structure. No temperature dependence was shown by either 13C NMR for A5[C(i) —C(3)] or by 1H NMR for substitution with deuterium at Cp). Thompson and Ford measured experimentally a variety of allylalkali metal compounds using variable-temperature NMR in THF-dx45. Addends such as TMEDA, hexamethylphosphoric triamide (HMPA), 15-crown-5-ether, [2.1.1]cryptand and n-butyllithium showed either no change in the spectrum or rapid decomposition of the complexing agent. Measurement of the populations of E (17) and Z (18) isomers of 1-isopropylallylpotassium showed the Z isomer to be more stable (Table 11). 

Metalation of 42 using -butyllithium or LDA provides an azaenolate that exists as a mixture of (Z)- and (E)-43. Alkylation followed by hydrolysis yields the optically active a,a-disubstituted carboxylic acid (.S )-44 in 72-80% ee (Scheme 2-25 and Table 2-7). 

A series of conjugated polyenes capped with chromophores and containing an androstane spacer were synthesized by Wittig or Wittig-type olefinations from epi-androsterone 5150. For example, vinyl carboxaldehyde 52, prepared from 51 in 60% yield as shown in equation 32, was treated with 9-anthrylmethylphosphonium bromide and n-butyllithium to give diene 53. Exocyclic diene 53 was subsequently oxidized to vinyl carboxaldehyde 54. The androsterone vinyl aldehyde intermediate could either be treated with a tetraphenylporphyrinpolyenyl phosphonium ylide, or, as shown below, the phosphonium salt of the androsterone (55) could be reacted with TPP polyeneal 56. The desired all-(E) isomer, 57, was obtained from the ( )/(Z)-isomeric mixture by chromatographic purification. 

A 1 1 mixture of (Z)- and ( )-tetramethylbicyclopropylidenes 24b,c was obtained by dihalocyclopropanation of dimethyl(dimethylethenylidene)cyclopro-pane 27 [45,46] followed by reduction of the adducts with sodium in methanol (Scheme 6). Addition of monochlorocarbene onto 2-(trimethylsilyl)-l-ethenyl-idenecyclopropane (29) proceeds with low diastereo- and regioselectivity to give a mixture of bicyclopropylidene and methylenespiropentane derivatives 30, 31 in poor yield [47]. Upon treatment of l,l-dibromo-2-methylpropene (36) with butyllithium at -110°C the unique diisopropylidenetetramethylbicyclo-propylidene 37 was formed by addition of isobutylidene to in situ generated tetramethylbutatriene (32), albeit in very low yield [48] (Scheme 7). 

The influence that a possible chelation has on the stereochemistry of the bromine-lithium exchange in dibromoaUcenes was first studied in the chiral MEM (methoxyethoxymethyl) ether 40. When this compound is treated with 1.2 equivalents of n-butyllithium in tetrahydrofnran, the acids E- and Z-42 are obtained in a ratio of 32 68 after carboxylation. Obvionsly, a kinetically favored substitution of the more easily accessible trans bromine atom occurs. When, however, slightly less than one equivalent (0.95-0.98 equiv) of -bntyllithinm is slowly added to a solution of 40 in diethyl ether at — 105°C, the -confignrated carbenoid 41 forms almost exclusively, and the carboxylic acids E- and Z-42 are obtained after reaction with dry ice in a ratio of over 99 1 (Scheme 9) ,i93 ... 

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. 

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