Lithium reaction with alkyl halides

Organocadmium compounds can be prepared from Grignard reagents or organo-lithium compounds by reaction with Cd(II) salts.180 They can also be prepared directly from alkyl, benzyl, and aryl halides by reaction with highly reactive cadmium metal generated by reduction of Cd(II) salts.181... 

Tin alkyl hydrides can be prepared from the halides by the reaction with lithium aluminum hydride. 

Alternatively alkyl halides undergo coupling reactions with lithium organ-ocuprates (which are prepared from alkyl halides) to give alkanes by carbon-carbon bond formation. Other metals can be used to promote the same kind of coupling, but die use of cuprates is the most efficient and general. 

Carboxylic acid dianions have also been alkylated by reaction with aziridines to give novel y-amino substituted acids in good yields508. Methoxybenzoic acids have also been alkylated in a reductive process by reaction with lithium in ammonia followed by treatment with an alkyl halide. The product formed in this one-pot reaction is an alkylated cyclohexa-2,5-diene carboxylic acid507. 

The best alkylating agents for silyl enol ethers are tertiary alkyl halides they form stable carbocations in the presence of Lewis acids such as TiCLj or SnCLj. Most fortunately, this is just the type of compounds that is unsuitable for reaction with lithium enolates or enamines, as elimination results rather than alkylation a nice piece of complementary selectivity. 

From alcohols. Alcohols can be transformed into phenylselenides in a stepwise manner via mesylation and reaction with lithium phenylselenolate. This procedure offers obvious advantages over the formation of the corresponding bromides or iodides when subsequent reaction with strong nucleophiles, such as organolithium compounds, are necessary to prepare the radical precursors. The diol 8 is converted to the bis(phenylselenide) 9 via the corresponding bis(mesylate) as shown in Scheme 2 [6]. Compound 9 is converted to the radical precursor 11 via reaction with lithium phenylacetylide followed by alkylation with allylbromide and a Pauson-Khand reaction. Such a reaction sequence would not be feasible with an alkyl halide. The cyclization afforded the expected tricyclic compound 12 in 95% yield. 

In a very interesting report of Molle and Bauer [7] using adamantyl halides and the hindered ketones hexamethylacetone and adamantanone, they observed no alcohol products when the hindered ketones were mixed with preformed adamantyl lithium at low temperature ( —20 C) in diethyl ether. However, when the ketones and halide were mixed with lithium powder under the same low-temperature conditions, substantial yields of the expected carbinols were isolated. They postulated a surface-mediated radical ion or radical pair reaction with the ketone or the ketyl radical. The reaction of a ketyl with the halide was ruled out because earlier researchers [4] had shown that no carbinol was obtained from the reaction of an alkyl halide and benzophenone ketyl. The authors also did not find any carbinol product when the ketyl of adamantanone was reacted with adamantyl halide. By extending their studies to other homologues of adamantane, the authors concluded that the stability of the cagelike radical species determined the extent to which the radical pathway is favored over the organometallic pathway. 

This is one of the many examples where it is preferable to use Grignard reagents over alkyllithium compounds for the alkylation of the heteroatom-functionalized Cp and related halide complexes, because of the risk of possible side-reactions with lithium alkyls. 

A significant property of the halomethylalanes is their reaction with lithium alkyls the complex salt formed from the etherate and a lithium alkyl immediately splits off lithium halide. Probably an aluminumylide ... 

The structurally novel bicyclic oxazinone was prepared based on D-glucopyranose. The lithium enolates of these compounds undergo highly diastereoselective alkylation reactions with reactive alkyl halides, in modest yields. Use of the phosphazene P4 base enhanced the yields of these processes, suggesting that metal enolate aggregation is at least partly... 

In that vein, it has been subsequently shown (by reactions which most probably involve a series of one electron transfer processes) that halogens can be stripped from almost any alkyl, alkenyl, or aryl halide by treatment with lithium (Li) or sodium (Na) in the presence of a proton donor such as (commonly used) 2-methyl-2-propanol (r-butanol [(CH3)3C-OH], r-BuOH). A solvent such as oxacyclopentane (THE) helps to moderate the reaction. Rearrangements of the carbon skeleton are common. Because it usually lacks selectivity, the method is only rarely used (unless the goal is destruction of the halogenated compound). 

The analogy extends toward their reaction with lithium dialkylcuprates. Just as alkyl halides react with lithium dialkylcuprates to form carbon-carbon bonds, so do a,p-unsaturated carbonyl compounds. 

Reactions of Halogeno-compounds.— In a reappraisal of the reduction of organic halides to alkanes with lithium aluminium hydride, clear solutions of LiAlH in THF have been observed to perform the reduction quantitatively and more rapidly than when using slurries of the reagent, as described in previous reports. The preferred stoicheiometry is LiAlH4 RHal = 1 1, so that the byproduct is aluminium hydride [equation (16)], which is inert to alkyl halides. 

The reaction of an alkyl halide with lithium is an oxidation-reduction reac tion Group I metals are powerful reducing agents... 

Reaction with an alkyl halide takes place at the metal surface In the hist step an election is transfeiied from lithium to the alkyl halide... 

Lithium diarylcuprates are prepared m the same way as lithium dialkylcuprates and undergo comparable reactions with primary alkyl halides... 

A key step in the reaction mechanism appears to be nucleophilic attack on the alkyl halide by the negatively charged copper atom but the details of the mechanism are not well understood Indeed there is probably more than one mechanism by which cuprates react with organic halogen compounds Vinyl halides and aryl halides are known to be very unreactive toward nucleophilic attack yet react with lithium dialkylcuprates... 

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. 

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