Ferf Butyllithium

The ferf-butyllithium was obtained from Alfa Inorganics, Inc. 

Bis[dimethylthienol]l,4,6,8-tetratellurafulvalene. 3,4-Dibromo-2,5 dimethylthiophene in tetrahydrofuran is treated at -78°C with 2 equiv of ferf-butyllithium. After 2 h, 1 equiv of tellurium powder is added. The mixture is slowly warmed to 0°C and kept at 0°C until all the tellurium has dissolved. The mixture is cooled again to -78°C, treated with tert-butyllithium and then with tellurium at 0°C. The ditellurolate solution is cooled to -78°C, mixed with 0.5 equiv of tetrachloroethene, stirred for 18 h and allowed to warm to 20°C. The brown solid is isolated by filtration and extracted with carbon disulphide. The extract is evaporated and the residue recrystallized from 1,1,2-trichloroethane to give bronze-coloured crystals. Yield 75% m.p. 295-298°C. 

To make neopentyllithium or any other alkyllithium from the corresponding iodoalkane, ferf-butyllithium is the best, if not the only choice (Tables 8 and 9). Besides its reactivity. 

The stereospecific construction of the trisubstituted double bond of the side chain at C-1 of carbazomadurins A (253) and B (254) was achieved using Negishi s zirconium-catalyzed carboalumination of alkynes 758 and 763, respectively. Reaction of 5-methyl-l-hexyne (758) with trimethylalane in the presence of zirconocene dichloride, followed by the addition of iodine, afforded the vinyl iodide 759 with the desired E-configuration of the double bond. Halogen-metal exchange with ferf-butyllithium, and reaction of the intermediate vinyllithium compound with tributyltin chloride, provided the vinylstannane 751a (603) (Scheme 5.79). 

Zask described a very clever and general approach to prepare 3-hydroxy-2(5H)-furanones in which he described the first report of a dianion of 179 that was utilized to prepare the key intermediate (Scheme 6.67, p. 116). After some experimentation he found that treatment of 179 with 2 equiv of ferf-butyllithium and 6 equiv of lithium chloride gave 319 that reacted cleanly with an ot-halo ketone to produce 320. Hydrolysis of 320 with refluxing 6 M hydrochloric acid then... 

Meyers and Shimano discovered the unusual deprotonation behavior of ethoxy-vinyllithium-HMPA complex (EVL-HMPA) for the deprotonation of the trans-oxazoline 366 and the cw-oxazoline 367. The EVL-HMPA complex is prepared by deprotonation of ethyl vinyl ether with ferf-butyllithium in THE followed by addition of HMPA. Reaction of the frani-oxazoline 366 with both the EVL-HMPA complex and conventional alkyllithium reagents (RLi) resulted in deprotonation at the benzylic 5-position. In contrast, deprotonation of 367 occurred at the 4-position with an alkyllithium reagent RLi, whereas benzylic deprotonation predominated with the EVL-HMPA complex (Scheme 8.117). ° The authors proposed that EVL-HMPA complexes with the 5-phenyl substituent prior to deprotonation. 

This model would predict higher selectvities for bulkier lithium reagents. Experimental data (Table 8.27 Scheme 8.146) supports this prediction. An unexpectedly lower selectivity was obtained when ferf-butyllithium was used to metalate ferf-butyl-substituted oxazolinylferrocene. In this particular case, the authors suggested that the reaction may proceed via oxygen directed or a nondirected pathway. 

Af,Af-Dimethyl-l-ferrocenylethylamine (5.22 g, 20 mmol) ferf-Butyllithium (1.62 M pentane solution) (15.0mL, 24mmol)... 

Pentafluoropropenyllithium could be prepared by lithium-hydrogen exchange of pentafluoropropene with -butyllithium in ether at -78°C [130], but a bulky base such as ferf-butyllithium or LDA had to be employed for the preparation of 2-pentafluoropropenyllithium from the corresponding 2-hydro-pentafluoropropene in ether and pentane solution at -78 °C [131] (Scheme 50). 

Organolithum compounds (lithium alkyls) are the most valuable initiators in anionic polymerization.120168 169172-175 Since living anionic polymerization requires the fastest possible initiation, sec- or ferf-butyllithium is usually used. Lithium alkyls add readily to the double bond of styrene [Eq. (13.32)] or conjugated dienes and form free ions or an ion pair depending on the solvent ... 

Unsubstituted tetrazolyl derivative 458 was also prepared according to the following procedure (91MIP2). A solution of 5-phenyl-2-trityltetrazole in tetrahydrofuran was first treated with 1.7 M ferf-butyllithium in pentane at -25°C, in two parts. After about 30 minutes, an organolithium salt precipitated. Then a 1 M ethereal solution of zinc chloride was added to the mixture, which was then warmed to room temperature. Bis(triphenyl-phosphine)palladium(Il) chloride and 4//-pyrido[l,2-a]pyrimidin-4-one 457 were added to the reaction mixture, and after boiling for 4 hours, the 2-trityl derivative of 458 was obtained in 56% yield. Finally, detritylation with a mixture of methanol and concentrated hydrochloric acid yielded tetrazole derivative 458. 

Aryl bromides can be converted to aryl Grignard or aryllithium compounds in three ways (Figure 5.34). In the first two methods the aryl bromide is reacted with Mg shavings or with Li wire, respectively (see Section 14.4.1 for the mechanism). In the third method—which is especially convenient for small-scale preparations—aryl bromides are converted into aryllithium compounds either with 1 equivalent of butyllithium (w-BiiLi) or with 2 equivalents of ferf-butyllithium (terf-BuLi) by the so-called Br/Li exchange reaction. 

Whilst carbamate derivatives of indoles and pyrroles are easily prepared, they have limited synthetic utility because they are easily attacked by nucleophiles. For example, A -Aloc525 and A -Cbz526 derivatives of tryptophan are known, but they are destroyed by piperidine. Boc derivatives of indoles, pyrroles and imidazoles are sufficiently hindered to be synthetically useful For example, N-Boc indole is stable towards piperidine and it can be metallated in the 2-position with ferf-butyllithium.527 Nevertheless, they are still more easily cleaved by nucleophiles than Boc-derivatives of secondary amines as illustrated by the fact that Boc-derivatives of pyrrole are cleaved with sodium methoxide, ammonia or hydrazine in methanol527 In tryptophan derivatives, the Ar>w-Boc group is less susceptible to aridolysis than an Na-Boc group with trifluoroacetic acid. However, the M"-Boc group can be cleaved selectively by thermolysis as illustrated by a step in a synthesis of Asperazine [Scheme 8,271 ].52 ... 

The largest volume commercial alkyllithium compound is n-butyllithium, but significant quantities of sec-butyl- and ferf-butyllithium are also produced. Production of n-butyllithium is achieved by reaction of n-butyl chloride with lithium metal as in eq 4.12 ... 

Di[o-(l-buten-3-ynyl)phenyl] ditellurides (generalprocedure). A ferf-butyllithium hexane solution (1.5 M, 14.7 mL, 22 mmol) was added dropwise over a 15-min period to a stirred solution of the above-obtained butenine (10 mmol) in anhydrous THF (50 mL) at - 80°C... 

Recently, Nakamura et al. successfully synthesized a regioisomer of kealiiquinone (Scheme 11) [50]. l-Methyl-2-phenylthio-lff-imidazole 44 was first converted into the 5-substituted imidazole 45, then the benzylic hydroxyl group in 45 was protected by a ferf-butyldimethylsilyl (TBDMS) group, and bromination with N-bromosuccinimide gave the bromide 46. Lithiation by ferf-butyllithium at the 4-position of 46 followed by trapping with 3,4-dimethoxy-2-(methoxymethoxy)benzaldehyde gave the tetrasubstituted imidazole 47 as a diastereomeric mixture. Acetylation of the hydroxy group of 47... 

Tris-or(/j< -lithiation of tris[2-(diethylsulfamoyl)phenyl]bismuthine with ferf-butyllithium followed by treatment with 3 equiv. of diaryliodobismuthine yields a branched tetrameric bismuthine, which, on similar treatment, leads to a dendrimer-type bismuthine [97CC2295],... 

Compared to 129, halogen-metal exchange with 2,3-diiodo-A -(phenylsulfonyl) indole (28) was more complicated [361] (Scheme 28). Treatment of 28 with one equivalent of ferf-butyllithium followed by ammonium chloride led to a (undetermined) mixture of 2-iodo-W-(phenylsulfonyl)indole (29a) and 3-iodo-Af-(phenylsulfonyl)indole (6). On the other hand, mixing 28 with excess ferf-butyl-lithium led to alkyne 132 via a facile ring fragmentation. 

The regioselectivity of bromine-lithium exchange reactions in dibromoindole substrates has been studied by Li [381, 382]. With both 4,7-dibromoindoles (e.g., 145) [382] and 5,7-dibromoindoles (e.g., 146) [381], bromine-lithium exchange occurs preferentially at C7 (Fig. 5) upon treatment with ferf-butyllithium. A similar result was reported recently by Lachance involving the selective chlorine-lithium exchange observed with 6-azaindole 147 [383]. 

The alkyl group to which lithium is bonded is fe/t-butyl, and so the name of this organometallic compound is ferf-butyllithium. An alternative, equally correct name is 1,1-dimethylethyllithium. 

The first total syntheses of two skyrins were presented by Nicolaou et al. in 2005 (554). For both, the same route was taken, which is shown in Scheme 12.6. The starting material was the chiral diester 816, which was MOM-protected and then regioselectively mono-hydrolyzed with porcine liver esterase. Oxidation of the remaining alcohol 817 with pyridinium chlorochromate, following elimination with diazabicyclo[5.4.0]undec-7-ene, gave the cyclohexenone 818 in good yield. The phenol 819 was first TBS-protected, and then the amide 820 was obtained from the acid chloride. With ferf-butyllithium and DMF, the corresponding aldehyde was formed, which was converted into the deprotected nitrile by treatment with TMSCN. 

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