Lithium-ammonia reduction halides

Furanoid and pyranoid glycals. The classical method for preparation of glycals is reduction of pyranosyl halides with zinc and acetic acid. A more recent method is lithium-ammonia reduction of furanosyl and pyranosyl halides with a blocking acetonide group. ... 

Reductive alkylation of carbon nanotubes using lithium and alkyl halides yields sidewall-functionalized nanotubes soluble in common organic solvents. Billups group prepared dodecylated SWCNTs from raw HiPCO tubes using lithium and dodecyl iodide in liquid ammonia and demonstrated the occurrence of exten-... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

One final example worth mentioning is the reductive alkylation/arylation with lithium and alkyl/aryl halides in liquid ammonia. This is a two-step process in which negatively charged nanotubes are formed via electron transfer from the metal. This step is relatively easy and fast due to the CNTs electron sink properties, and it enables exfoliation of the tubes through electrostatic repulsion in the second stage, the alkyl/aryl halides react with the charged tubes to form a radical anion which can dissociate into the alkyl radical and the halide anion, with the former species undergoing addition to the CNT sidewalls [42]. 

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. 

Lithium and sodium dissolved in liquid ammonia have been extensively employed in the reduction of benzylic hydroxyls, carbonyl compounds and acetals. These reductions have been reviewed. Overreduction of benzyl alcohols by Li/NHa to 1,4-dihydro derivatives can be avoided using an ammonium chloride quench. Aryl halides are unstable under these conditions. 

A commonly used synthetic method for these substituted phosphines involves the deprotonation of phosphine (or methylphosphine ) by a sodium-ammonia solution, followed by treatment with a methyl halide. More recently, methylphosphine has been produced by the reduction of methyldichloro-phosphine (unfortunately, not a readily available compound) by lithium hydroaluminate. The present method is essentially the deprotonation-methylation procedure, but instead of sodium-ammonia solutions, relatively easily handled KOH-dimethyl sulfoxide suspensions are used. 

The Birch reduction of aromatic hydrocarbons or of double bonds with alkali metals in liquid ammonia or amines [37] resembles in yield and selectivity the cathodic reduction with lithium halide as supporting electrolyte (for example, Ref. 38). 

Phenylmenthol is the auxiliary in an asymmetric Birch reduction of pyrroles by Donohoe37 Lithium in ammonia does the reduction and the enolate is trapped with various alkyl halides. Hydrolysis of the esters 227 releases the enantiomerically enriched (78-90% ee) dihydropyrroles 228 in good yield. Furans give similar products with a C2 symmetric amine as auxiliary. This should become a general route to a variety of heterocycles. 

Sodium/ammonia" treatment also causes disruption of the ring in thiophene and simple thiophenes, however thiophene-2-carboxylic acid and 2-acyl-thiophenes can be converted into the 2,5-dihydro derivatives using lithium in ammonia, followed by protonation or trapping with an alkyl halide."" Side-chain reductions can be carried out with metal hydrides, which do not affect the ring. 

Addition of an alkyl group at C17 initially involves conditions fairly similar to those used in the Birch reduction of enones. A solution of the steroid in liquid ammonia and some inert co-solvent is first treated with lithium metal (Scheme 6.20). The resulting anion 20-1 is then quenched with an alkyl halide instead of the alcohol usually employed in Birch reductions. The anion at C17 then displaces the halogen, in the case at hand iodide, from the alkyl group to form a carbon-carbon bond and the 17a-methyl derivative 20-2. 

---