Alkyllithiums preparation

Nakai and coworkers90 have demonstrated that the carbanion cyclization of enantio-enriched a-(homoallyloxy)alkyllithiums, prepared from the corresponding stannanes 192, proceeds with complete retention of configuration at the lithium-atom-bearing carbon centre. The obtained tetrahydrofurans 193 are formed with high trans-selectivity and without losing the enantiomeric purity. This means that the lithium might coordinate to the... 

Table 1. Primary Alkyllithiums Prepared from Li Metal with Organic Halides...

The lithiation of allene can also be carried out with ethyllithium or butyl-lithium in diethyl ether (prepared from the alkyl bromides), using THF as a cosolvent. The salt suspension which is initially present when the solution of alkyllithium is cooled to -50°C or lower has disappeared almost completely when the reaction between allene and alkyllithium is finished. 

In the first stage of the preparation one molar equivalent of alkyllithium displaces halide from copper to give an alkylcopper(I) species... 

The organoborate intermediates can also be generated from alkenylboronic esters and alkyllithium or Grignard reagents, or from ttialkylboranes and alkenyllithium compounds. Conjugated symmetrical and unsymmetrical diynes (289—291), stereochemically pure 1,3-dienes (292,293), and 1,3-enynes (294) including functionali2ed systems can be prepared (289,295). 

Anionic polymerization of vinyl monomers can be effected with a variety of organometaUic compounds alkyllithium compounds are the most useful class (1,33—35). A variety of simple alkyllithium compounds are available commercially. Most simple alkyllithium compounds are soluble in hydrocarbon solvents such as hexane and cyclohexane and they can be prepared by reaction of the corresponding alkyl chlorides with lithium metal. Methyllithium [917-54-4] and phenyllithium [591-51-5] are available in diethyl ether and cyclohexane—ether solutions, respectively, because they are not soluble in hydrocarbon solvents vinyllithium [917-57-7] and allyllithium [3052-45-7] are also insoluble in hydrocarbon solutions and can only be prepared in ether solutions (38,39). Hydrocarbon-soluble alkyllithium initiators are used directiy to initiate polymerization of styrene and diene monomers quantitatively one unique aspect of hthium-based initiators in hydrocarbon solution is that elastomeric polydienes with high 1,4-microstmcture are obtained (1,24,33—37). Certain alkyllithium compounds can be purified by recrystallization (ethyllithium), sublimation (ethyllithium, /-butyUithium [594-19-4] isopropyllithium [2417-93-8] or distillation (j -butyUithium) (40,41). Unfortunately, / -butyUithium is noncrystaUine and too high boiling to be purified by distiUation (38). Since methyllithium and phenyllithium are crystalline soUds which are insoluble in hydrocarbon solution, they can be precipitated into these solutions and then redissolved in appropriate polar solvents (42,43). OrganometaUic compounds of other alkaU metals are insoluble in hydrocarbon solution and possess negligible vapor pressures as expected for salt-like compounds. 

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. 

Many other kinds of organometallic compounds can be prepared in a manner similar to that of Grignard reagents. For instance, alkyllithium reagents, RLi, can be prepared by the reaction of an alkyl halide with lithium metal. Alkyllithiums are both nucleophiles and strong bases, and their chemistry is similar in many respects to that of alkylmagnesium halides. 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

The anti diastereoselectivity is improved to a 6 1 ratio by the addition of triethylborane to the reaction mixture83. NMR-spectroscopic investigations indicate that a boronate complex is the decisive intermediate84, since it can also be prepared by the addition of alkyllithium to the dialkyl(2-butenyl)borane (path ). 

Another group of Japanese workers91 found that the sulphoxonium salt, 7, was reducible to sulphoxides with either alkyllithiums or lithium dialkylcuprates, the exact reaction pathway being complicated by halide ions originating from the preparation of the metal alkyls. However, good yields of methyl phenyl sulphoxide were obtained by reduction of 7 with sulphur dioxide or a thiol in pyridine (equation 37). 

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... 

Another way is to dissolve an alkylcopper compound in an alkyllithium solution. Higher order cuprates can also be prepared, as well as non-ate copper reagents. Metallocenes (see p. 53) are usually made by this method ... 

K or Li, as well as with Zn—Me3SiCl and with certain compounds prepared from WCle and either lithium, lithium iodide, LiAlH, or an alkyllithium (see 17-17). The reaction has been used to convert dialdehydes and diketones to cycloalkenes. Rings of 3-16 and 22 members have been closed in this way, for example. 

---