Substitution alkyllithiums

Alkyllithium reagents can also be generated by reduction of sulfides.32 Alkenyl-lithium and substituted alkyllithium reagents can be prepared from sulfides,33 and sulfides can be converted to lithium reagents by the catalytic electron transfer process described for halides.34... 

A variety of localized lithiated carbanions, such as aryllithiums and sulfur- and silicon-substituted alkyllithiums, have been found, by application of C, Li, and Li NMR techniques, to form triple ions in THF-HMPA solution. Thus, change to triple ion structures (18a-g) could be discerned as HMPA (2-5 equiv.) was added to solutions of monomeric structures (17a-g) in 4 1 THF-diethylether. The amount of triple ion is sensitive to ortho substitution monomeric (17a) and (17b) form 65-80% triple ion in presence of 1-3 equiv. HMPA whereas (17c) and (17e) form less than 20% at 5 equiv. HMPA. Pyridylthio-substituted carbanion (19) forms bis-chelated triple ion (20). 

Tris-metallomethanes, e.g., (Ph3Pb)3CH , (Ph3Pb)2CHAsPh2 (PhSe)3CH, and tetra-kis-metallomethanes, e.g., (PhSe)4.C, also undergo transmetallations (see Table 4). Seleno-substituted alkyllithiums are prepared by transmetallation . Tetrathioalkoxymethanes react similarly with RLi ... 

Among the compounds produced by the halogen-metal exchange route are a-substituted alkyllithiums, where the a-substituent is RS , RSe , ROjC , RjSi , RjGe , RjSn or RjPb (see Table 1). 

Table 1. Formation of Substituted Alkyllithiums via Halogen-Lithium Exchange... 

Reaction of alkyl- or arylmagnesium halides with bicyclic )V,0-acetals 2 gave the expected alkyl or arylbicyclo[n.l.O]alkylamines 3,22.4-4,45 endo-. v avlO compounds were formed in this reaction the cis or trans linkage of the bicyclic systems was not influenced by the substitution. Alkyllithiums failed to react with the A(,0-acetals. An aminoalkylation of alkyl-lithiums, however, was reported in the substitution of the tetrazole moiety in (7-mor-pholinobicyclo[4.1.0]hept-l-yl)tetrazole by alkyllithium. ... 

Oxygen-substituted alkyllithium derivatives of type 2 were the first chiral car-banions which were accessible in enantiopure form and proved to be configurationally stable, at least at temperatmes below -40°C [Eq. (1)] Still and Sreeku-mar cleaved (J )-l-(benzyloxymethoxy)-l-tributylstannylpropane (1) with n-butylUthiiun and trapped the intermediate lithium compound 2 [1] by dimethyl sulfate to give the BOM ether of (S)-2-butanol (3) [2,3]. 

Alkenyllithium and substituted alkyllithium reagents can be prepared from sulfides. The method can also be applied to unsubstituted alkyllithium reagents, although in this case there is no special advantage over the conventional procedure. 

Our preferred initiators were generally prepared from 1,1-diphenyl ethylene by addition of n-butyllithium or specially synthesized substituted alkyllithium reagents (see below). The ready availability of diphenyl ethylene and commercial standard n-butyllithium solutions precludes the need for elaborate apparatus for initiator generation such as described by Galluccio and Glusker in Macromolecular Synthesis. ... 

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

The second molar equivalent of the alkyllithium adds to the alkylcopper to give a neg atively charged dialkyl substituted derivative of copper(I) called a dialkylcuprate It is formed as its lithium salt a lithium dialkylcuprate... 

Silanes react with alkyllithium compounds, forming various alkylsilanes. Complete substitution is generally favored however, less substituted products can be isolated by proper choice of solvent. AH four methylsHanes, vinylsHane [7291-09-1and divinylsilane [18142-56-8] have been isolated from the reaction of SiH and the appropriate alkyllithium compound with propyl ether as the solvent (35). MethylsHane and ethyldisHane [7528-37-2] have been obtained in a similar reaction (36). 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

The first clearly authenticated preparation of an isoindole was reported by Wittig et in 1951. It was found that elimination from isoindolinium bromides and iodides with bases such as aryl- and alkyllithium afforded 2-substituted isoindoles in variable yields. For instance, 2,2-dimethylisoindolinium bromide (5) on treatment with one equivalent of phenyllithium in ether under nitrogen, evolved methane and gave 2-mcthylisoindole (6) in 74% yield. With methyl-lithium as base, a slightly lower yield was obtained. 

The importance of metal catalysis is suggested by the fact that exclusive 4-substitution of pyridine with alkyllithiums or alkyl-magnesium halides occurs when free metal is present exclusive 2-substitution otherwise occurs. 

These reagents are not isolated but are used directly in reactions with aldehydes, after generation of ate complexes via the addition of an alkyllithium reagent or pyridine11. 2-(2-Propenyl)-1,3,2-dioxaborolane is also metalated upon treatment with lithium tetramethylpiperidide, but mixtures of a- and y-substitution products are obtained upon treatment of this anion with alkylating agents20. Consequently, this route to a-substituted allylboron compounds appears to be rather limited in scope. 

A flame-dried flask under argon containing a 0.08 M THF solution of 317 mg (1.0 mmol) of the 2-(l- or 2-naphthyl)-substituted 4,5-dihydrooxazole is cooled to a temperature of between — 80 and 0 CC (see ref 7) and is treated with 1.5-2.0 equiv of the alkyllithium. The solution becomes deep red over 2-4 h and is quenched by the dropwise addition of 1.5 equiv of the electrophile (either neat or as a THF solution). The temperature is maintained for 1 h and then the solution is warmed gradually to 0 JC. The solution is diluted with 100 mL of diethyl ether and washed with 5 mL of sat. NH4C1, followed by 3 mL of sat. aq NaCI. The combined aqueous layers are back-extracted with 10 mL of CII2C12, and the combined extracts are dried over Na2S04. Concentration of the filtrate in vacuo provides a yellow oil, which is flash chromatographed over silica gel (1 -10% ethyl acetate in hexane) to yield the desired adducts. The diastereomeric ratios are determined by HPLC (Zorbax Sil column, Du Pont). 

The addition reactions of alkyllithium-lithium bromide complexes to a-trimethylsilyl vinyl sulfones that have as a chiral auxiliary a y-mono-thioacetal moiety derived from ( + )-camphor are highly diastereoselective. A transition state that involves chelation of the organolithium reagent to the oxygen of the thioacetal moiety has been invoked. The adducts are readily converted via hydrolysis, to chiral a-substituted aldehydes22. 

The predictable stereochemistry of the ring closure of substituted 5-hexenyllithiums, coupled with the ease with which the product organolithium may be functionalized, permits rational design of synthetic routes to polycyclic systems by sequential anionic cyclizations of polyolefinic alkyllithiums.12 The preparation of stereoisomerically pure e do-2-substituted bicyclo[2.2.1]heptanes is illustrative of this approach to polycyclic systems.12... 

The latter reagent also methylates certain heterocyclic compounds (e.g., quinoline) and certain fused aromatic compounds (e.g., anthracene, phenanthrene). The reactions with the sulfur carbanions are especially useful, since none of these substrates can be methylated by the Friedel-Crafts procedure (11-12). It has been reported that aromatic nitro compounds can also be alkylated, not only with methyl but with other alkyl and substituted alkyl groups as well, in ortho and para positions, by treatment with an alkyllithium compound (or, with lower yields, a Grignard reagent), followed by an oxidizing agent such as Bra or DDQ (P- 1511). 

Later work examined substituent effects on kinetically controlled alkylations [68, 69] (Scheme 32). Substitution at the 5-position is well tolerated in these reactions. Reductive lithiation of a series of 4-phenylthio-l,3-dioxanes and quenching of the axial alkyllithium intermediate with dimethyl sulfate provided the flzzfz -l,3-diols in good yield, with essentially complete selectivity. 

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