Of methyllithium

Methyllithium. MethyUithium [917-54 ] CH Li, crystallizes from benzene or hexane solution giving cubic crystals that have a salt-hke constitution (128). Crystalline methyllithium molecules exist as tetrahedral tetramers (129). Solutions of methyllithium are less reactive than those of its higher homologues. Methyllithium is stable for at least six months in diethyl ether at room temperature. A one-molar solution of methyllithium in tetrahydrofuran (14 wt %) and cumene (83 wt %) containing 0.08 M dimethyknagnesium as stabilizer loses only 0.008% of its activity per day at 15°C and is nonpyrophoric (117). 

Although ethereal solutions of methyl lithium may be prepared by the reaction of lithium wire with either methyl iodide or methyl bromide in ether solution, the molar equivalent of lithium iodide or lithium bromide formed in these reactions remains in solution and forms, in part, a complex with the methyllithium. Certain of the ethereal solutions of methyl 1ithium currently marketed by several suppliers including Alfa Products, Morton/Thiokol, Inc., Aldrich Chemical Company, and Lithium Corporation of America, Inc., have been prepared from methyl bromide and contain a full molar equivalent of lithium bromide. In several applications such as the use of methyllithium to prepare lithium dimethyl cuprate or the use of methyllithium in 1,2-dimethyoxyethane to prepare lithium enolates from enol acetates or triraethyl silyl enol ethers, the presence of this lithium salt interferes with the titration and use of methyllithium. There is also evidence which indicates that the stereochemistry observed during addition of methyllithium to carbonyl compounds may be influenced significantly by the presence of a lithium salt in the reaction solution. For these reasons it is often desirable to have ethereal solutions... 

The reaction of lithium with methyl chloride in ether solution produces a solution of methyllithium from which most of the relatively insoluble lithium chloride precipitates. Ethereal solutions of halide-free" methyllithium, containing 2-5 mole percent of lithium chloride, were formerly marketed by Foote Mineral Company and by Lithium Corporation of America, Inc., but this product has been discontinued by both companies. Comparable solutions are also marketed by Alfa Products and by Aldrich Chemical Company these solutions have a limited shelf-life and older solutions have often deteriorated... 

Seven procedures descnbe preparation of important synthesis intermediates A two-step procedure gives 2-(HYDROXYMETHYL)ALLYLTRIMETH-YLSILANE, a versatile bifunctional reagent As the acetate, it can be converted to a tnmethylenemethane-palladium complex (in situ) which undergoes [3 -(- 2] annulation reactions with electron-deficient alkenes A preparation of halide-free METHYLLITHIUM is included because the presence of lithium halide in the reagent sometimes complicates the analysis and use of methyllithium Commercial samples invariably contain a full molar equivalent of bromide or iodide AZLLENE IS a fundamental compound in organic chemistry, the preparation... 

The dry tosylhydrazone (20 g, 45.5 mmol) is dissolved in 750 ml of 1,2-dimethoxyethane (freshly distilled from lithium aluminum hydride) in a flame-dried 1 liter round bottom flask fitted with a 240 ml addition funnel, a drierite tube and a magnetic stirrer. A 2.05 M ether solution of methyllithium (130 ml, Alfa Inorganics, Inc.—Caution to avoid the mineral oil impurity the methyllithium solution is decanted from a cold solution which contains a precipitate) is placed in the dropping funnel and added over a 60 min period. The temperature of the reaction mixture increases to ca. 35° during the addition however, no cooling precautions are required. The highly colored reaction mixture is stirred for 7 hr and then poured into 1.5 liters of ice water. The flocculent precipitate is digested for 12 hr at room temperature to speed the filtration. After filtration the filter cake is washed with 500 ml water and dried under vacuum at 50° for several hr. The androsta-5,16-dien-3l5-ol is obtained in ca. 70% yield after recrystallization from methanol mp 138-139°. 

Kondrat eva pyridine synthesis. This methodology to pyridine rings continues to be applied in total synthesis. An approach to the antitumor compound ellipticine 34 ° makes use of a Diels-Alder reaction of acrylonitrile and oxazole 32 to form pyridiyl derivative 33. Addition of methyllithium and hydrolysis transforms 33 into 34. 

Sdieire 3.47. Copper ar nethiolat -catalyz d conjugate additionc of methyllithium to iznynoatizc [194]. 

The stage is now set for the crucial polycyclization event. Tertiary carbinol 8, derived from the action of methyllithium on enone 9, is a rather unstable substance, and it was submitted to the polycyclization reaction without purification. When intermediate 8 is treated with trifluoroacetic acid (TFA) and the vinyl cation trapping agent ethylene carbonate in 1,2-dichloroethane at 0°C, the desired... 

The completion of the synthesis of the polyol glycoside subunit 7 requires construction of the fully substituted stereocenter at C-10 and a stereocontrolled dihydroxylation of the C3-C4 geminally-disub-stituted olefin (see Scheme 10). The action of methyllithium on Af-methoxy-Af-methylamide 50) furnishes a methyl ketone which is subsequently converted into intermediate 10 through oxidative removal of the /j-methoxybenzyl protecting group with DDQ. Intermediate 10 is produced in an overall yield of 83 % from 50) , and is a suitable substrate for an a-chelation-controlled carbonyl addition reaction.18 When intermediate 10 is exposed to three equivalents of... 

In a similar manner, 10-methyldibenz[Z>,/ oxepin (4) can be obtained from dibenz[6,/]oxepin-10-(1 l//)-one after addition of methyllithium and subsequent iodine-catalyzed dehydration.161... 

Precomplexation of 2-butylcyclopentanone with methylaluminum bis(2,6-di-hrt-butyI-4-methylphenoxide) (MAD), prior to the addition of methyllithium, leads to the exclusive formation of the equatorial alcohol via cis attack3 4. However, this methodology is apparently not applicable to 3-substituted cyclopentanones. Thus, addition of propylmagnesium bromide to... 

In accord with the Felkin-Anh model, a-chiral ketones react more diastereoselectively than the corresponding aldehydes. Increasing steric demand of the acyl substituent increases the Cram selectivity. Due to the size of the acyl substituent, the incoming nucleophile is pushed towards the stereogenic center and therefore the diastereoface selection becomes more effective (see also Section 1.3.1.1.). Thus, addition of methyllithium to 4-methyl-4-phenyl-3-hexanonc (15) proceeds with higher diastercoselectivity than the addition of ethyllithium to 3-methyl-3-phenyl-2-pen-tanone (14)32. 

The fact that only Grignard reagents add with high diastereoselectivity to the phenylmenthyl ester of glyoxylic acid, whereas methyllithium reacts nonstereoselectively, may be the result of a different aggregation of the reagents. This is supported by the tremendous improvement of the stereoselectivity when the addition of methyllithium is undertaken in the presence of lithium perchlorate13. 

Since the addition of methyllithium, as well as the addition of dimethylmagnesium, to benzaldehyde (11) proceeded with very low enantioselectivity compared to other organometal-... 

Addition of methyllithium to the enantiomerically pure arene dicarbonylchromium chelate 2, prepared by irradiation of imine l52 [derived from ( 1 )-(S)-tricarbonyl(2-methylbenzalde-hyde)chromium53] and subsequent removal of the chromium moiety provides amine 3 in 72% yield and 94% ee54. Interestingly, addition of methyllithium to imine 1 affords only racemic 3. 

In order to prove the utility of this method and to ascertain the absolute configuration of the products, (S)-alanine has been enantioselectively prepared. The key step is the addition of methyllithium to the AjA -dimethyl hydrazone acetal 4c, derived from diol 3c. In accordance with 13C-NMR investigations it can therefore be assumed that all major diastereomers resulting from the addition of organolithium reagents to hydrazone acetals 4a-c derived from diols 3a, 3b or 3c (Table 3, entries 1 -6) have an S configuration at the newly formed stereogenic center. 

The addition of methyllithium to -alkoxy-a-(trimethylsilyl)-of/ unsaturated sulfones, 3-alkoxy-5-phenyl-l-phenylsulfonyl-l-(trimethylsilyl)-l-pentene and subsequent desilylation gives syn-products. The syn to anti diastereoselectivity is generally high and essentially independent of the nature of the y-alkoxy substituent8-13. 

Addition of methyllithium to an enantiomerically pure vinyl sulfone to give the yv -adduct was a key step in the total synthesis of (-)-maytansinol14. 

Addition of methyllithium to a cyclic /i, y -epoxy-a,/i-unsaturated sulfone gave predominately the m-alcohol as product20. 

Mono- and l,3-di-ter/-butylcyclopentadienyllithium Li(Bu Cp) 4 (n = 1) and 5 (,n = 2) can be obtained directly by addition of methyllithium to 6,6-dimethyl fulvene and 2-/ert-butyl-6,6-dimethyl fulvene, respectively [27a]. Since the fulvenes themselves are easily accessible by base-induced condesation reactions [27b], this method offers a viable alternative to the usual metalation of the substituted cyclopentadienes 1 and 2 (Eq. 2). 

Isobe and coworkers407 found an interesting diastereoselective heteroconjugate addition of methyllithium to 314. The stereochemical control was considered to be determined at the stage of the intermediate 315. Since methyllithium is considered to be coordinated strongly with the methoxyethoxymethoxyl (OMEM) group, the methyl anion would attack the -carbon of the olefin only from one side, as shown below. 

MeTi(OiPr)3] must be used in pure form rather than as a solution in hexane. Titanium tetraisopropoxide (95%) was obtained from ABCR, Karlsruhe by the submitters and from Aldrich Chemical Company by the checkers and was distilled under nitrogen before use. Titanium tetrachloride (>99%) was purchased from VWR by the submitters and from Aldrich Chemical Company by the checkers and was used without further purification. The submitters obtained a solution of methyllithium in ether (1.6M, 5 wt%) from Fluka. 

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