Alkyllithium 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]. 

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... 

Alternative conditions for reductive decyanations can be used. The allylic ether in compound 26, an intermediate in a total synthesis of (-)-roxaticin, was prone to reduction when treated with lithium in liquid ammonia. Addition of the substrate to an excess of lithium di-ferf-butylbiphenylide in THF at -78°C, and protonation of the alkyllithium intermediate provided the reduced product 27 in 63% yield, as a single diastereomer (Eq. 7). a-Alkoxylithium intermediates generated in this manner are configurationally stable at low temperature, and can serve as versatile synthons for carbon-carbon bond forming processes (see Sect. 4). 

The reaction of alkyllithium reagents with diaryl or alkyl aryl sulphoxides results in a displacement of the aromatic group by the alkyl group from the alkyllithium (equation 369) . Johnson and coworkers ° were the first to apply this reaction for the synthesis of optically active alkyl methyl sulphoxides. Later on. Durst and coworkers found that the aromatic group which can best carry a negative charge is the most readily displaced, and that the lowest yields of displacement were observed when methyllithium was used as a nucleophilic reagent. The results are summarized in Table 28. 

The synthesis of unsymmetrical ketones can be carried out in a tandem one-pot process by successive addition of two different alkyllithium reagents.115... 

The most studied catalyst family of this type are lithium alkyls. With relatively non-bulky substituents, for example nBuLi, the polymerization of MMA is complicated by side reactions.4 0 These may be suppressed if bulkier initiators such as 1,1-diphenylhexyllithium are used,431 especially at low temperature (typically —78 °C), allowing the synthesis of block copolymers.432,433 The addition of bulky lithium alkoxides to alkyllithium initiators also retards the rate of intramolecular cyclization, thus allowing the polymerization temperature to be raised.427 LiCl has been used to similar effect, allowing monodisperse PMMA (Mw/Mn = 1.2) to be prepared at —20 °C.434 Sterically hindered lithium aluminum alkyls have been used at ambient (or higher) temperature to polymerize MMA in a controlled way.435 This process has been termed screened anionic polymerization since the bulky alkyl substituents screen the propagating terminus from side reactions. 

A very simple and straightforward access to enantiopure substituted pyrrolidines and piperidines was obtained by reaction of phenylglycinol 178 with co-chloroketones 179. The intermediate oxazolidines 180 were then easily converted into the desired compounds <00EJO1719>. Compound 182 was obtained by reaction of the correspondent oxazolidine with a complex alkyllithium derivatives and was the intermediate for the synthesis of... 

The synthesis of alkali metal organophosphides and arsenides is usually most conveniently achieved by the direct metalation of a primary or secondary phosphine/arsine with a strong deprotonating agent such as an alkyllithium or an alkali metal hydride ... 

Enantioselective synthesis of R R2CHNH2.1 Alkyllithiums add stereoselec-tively to the C=N bond of SAMP hydrazones (2) of aldehydes. Reductive cleavage of the N—N bond of the products (3) affords either (R)- or (S)-4 with recovery of... 

The reaction was used for synthesis of (- )-norpseudoephedrine from a chiral a-hydroxy aldehyde (second example). The diastereoselectivity can be reversed by addition of alkyllithiums to a-trityloxy aldehydes, presumably because chelation with the oxygen atom is no longer possible. 

The alkyllithium-initiated, anionic polymerization of vinyl and diene monomers can often be performed without the incursion of spontaneous termination or chain transfer reactions (1). The non-terminating nature of these reactions has provided methods for the synthesis of polymers with predictable molecular weights and narrow molecular weight distributions (2). In addition, these polymerizations generate polymer chains with stable, carbanionic chain ends which, in principle, can be converted into a diverse array of functional end groups using the rich and varied chemistry of organolithium compounds (3). 

Various commercially available compounds containing C—Li bonds are listed in Table 1. The alkyllithium and aryllithium species listed there are usually very reactive. These compounds serve to prepare in situ other intermediate reagents. These proceedings may afford various advantages in organic synthesis, such as better control of the reaction path, increased stereochemical selectivity and the possibility of working at higher temperatures. 

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