Lithium, reductions in amine solvents

Lead tetraacetate, oxidation of a hydrazone to a diazo compound, 50, 7 Lithio ethyl acetate, 53, 67 Lithium, reductions in amine solvents, 50, 89 Lithium aluminum hydride, reduction of exo-3,4-dichloro-bicyclo-[3.2.l]oct-2-ene to 3-chlorobicyclo[3.2.l]oct-2-ene, 51, 61... 

Lithio ethyl acetate, 53, 67 Lithium, reductions in amine solvents, 50, 89... 

Lithium dissolved in amines of low molecular weight constitutes a useful and convenient reagent for reducing aromatic hydrocarbons to monoolefins.6 Although mixtures of isomeric olefins are usually obtained with primary amine solvents, the use of secondary amines as cosolvents dramatically increases the selectivity of these reductions so that the more thermodynamically stable olefin usually becomes the predominant product. Thus, in the reduction of naphthalene, the amount of A9,10-octalin increases from 52% when pure ethylamine is the solvent to 80-82% when the solvent is an ethylamine-dimethylamine mixture. As another example, the reduction of f-butylbenzene with lithium in pure ethylenediamine produces a product containing 70% of 1-f-butylcyclohexene.7 When a mixture of ethylenediamine and morpholine is used as the reaction solvent, the product contains 84% of 1-f-butyleyclohexene.8... 

Alkylthio groups can be removed (equation 21) by reaction of the a-alkylthio ketone with either zinc in wet ether in the presence of TMS-Cl, lithium in amine solvents or in THF containing an electron mediator such as naphthalene or trimesitylborane, or Na(Hg) in methanol buffered with Na2HP04. The enolate formed by Li reduction in NHa can be alkylated (equation 22). ... 

Just as lithium and sodium can be used in low molecular weight amines for reduction of alkynes, calcium is an effective reducing agent in amine solvents. Reaction of 2-nonyne with a calcium-methylamine-ethylenediamine mixture gave 87% yield of an 86 8 4 mixture of trans-2-nonene/traMs-3-nonene/tra 5 -4-nonene, the latter two products arising by bond isomerization. 98... 

The less hindered f/ans-olefins may be obtained by reduction with lithium or sodium metal in liquid ammonia or amine solvents (Birch reduction). This reagent, however, attacks most polar functional groups (except for carboxylic acids R.E.A. Dear, 1963 J. Fried, 1968), and their protection is necessary (see section 2.6). 

Polystyrene-bound amides, including peptides, can be reduced to the corresponding amines by treatment with borane in ethereal solvents. Other reagents, such as lithium aluminum hydride, are less convenient for reductions on insoluble supports, because insoluble precipitates can readily form and clog frits. Carbamates, tert-butyl ethers or thioethers, and trityl or benzhydryl amines remain unchanged upon treatment with borane, but carboxylic esters may undergo partial or complete reduction [178],... 

Although catalytic hydrogenation in the presence of H2 and a catalyst such as Pt, Pd, Ni or Ru, reaction with diborane, and reduction by lithium, sodium or potassium in hydroxylic or amine solvents have all been reported to convert carbonyl compounds into alcohols, the most common reagents used for the reduction of carbonyl compounds are hydride donors. 

Electrochemical methods for the reduction of aromatic substrates utilizing ammonia and amines as solvents with lithium salts as electrolytes have been successful. Toluene was reduced to the 2,5-dihydro derivative in 95% yield in methylamine-lithium chloride if an undivided cell was used, while a 53 47 mixture of 3- and 4-methylcyclohexenes was formed in a divided cell.. Of greater interest, however, are attempts to achieve these reductions in aqueous media. In one experiment utilizing a two-phase mixture of substrate in aqueous tetra-n-butylammonium hydroxide and a mercury cathode, anisole was reduced on a preparative scale (15 g) to its 2,5-dihydro derivative in 80% yield. The optimal temperature for most reductions appeared to be 60 °C and under these conditions, even suspensions of high molecular weight substrates could be successfully reduced, e.g. steroid (226) afforded a >90% chemical yield of (227). Much higher coulombic yields were obtained when a small amount of THE was added to the mixture, however. 

Recent advances in reductions with calcium dissolved in different amine solvents demonstrate value of calcium in organic synthesis. Use of calcium provides a better chance of chemoselectivity than use of lithium and sodium. The reaction conditions are also milder for calcium than for lithium and sodium. It is expected that, in the coming decade, organic chemists will continue to find that use of calcium in a variety of reaction media has advantages in the synthesis of complicated compounds of significance. 

Tri-O-benzyl-L-galactitol was converted into the isopropylidene mesylate 24. Treatment of 24 with lithium azide in DMF gave the azide 25 with inversion of the configuration. Reduction of the azide 25 with lithium aluminum hydride gave the amine 26 To protect the amino group, N-ethoxycarbonylphthalimide was used with triethylamine as solvent to give the phthaloyl derivative 27... 

Alkynes can also be reduced to alkenes by using either sodium or lithium metal in liquid ammonia or in low-molecular-weight primary or secondary amines. The alkali metal is the reducing agent and, in the process, is oxidized to M, which dissolves as a metal salt in the solvent for the reaction. Reduction of an alkyne to an alkene by lithium or sodium in liquid ammonia, NH3(Z), is stereoselective it involves mainly anti addition of two hydrogen atoms to the triple bond. 

Due to the low oxidation state of the metal in carbonyliron complexes and ferrates, these species can be applied for the reduction of various carbonyl compounds. Initially, these reagents have been applied in stoichiometric amounts. First examples describe the hydrogenation of a,p-unsaturated carbonyl compounds by carbonyl(hydrido)ferrate complexes to give saturated carbonyl compounds or saturated alcohols. Low valent iron species for the reduction of carbonyl compounds and imines can also be generated in situ from iron(II) chloride and lithium powder in the presence of 4,4 -di-rert-butylbiphenyl. Catalytic versions have been developed subsequently. Thus, pentacarbonyliron functions as a precatalyst for the hydrogenation of aldehydes and ketones in the presence of a tertiary amine as solvent (Scheme 4-322). The catalytically active system probably consists of (tetracarbonyl)(hydrido)ferrate and the protonated amine. ... 

In general, the rates of reduction by the ammonium salts are slower than those attained under normal conditions with the lithium salts, but the use of a non-ethereal solvent can be an advantage. Quaternary ammonium aluminium hydrides reduce ketones and amides effectively to alcohols and amines. Nitriles are also reduced to amines, whereas haloalkanes and arenes are reductively dehalogenated to give hydrocarbons in high yield [3]. 

The cis-fagaramide (J) was synthesized as outlined below. The required acetylenic acid (c) was prepared from piperonal (a) by the Corey s procedure.Treatment of piperonal with carbon tetrabromide, triphenylphosphine and zinc gave the bromo olefin (b) as an oil in 71% yield. The bromo olefin (b) was treated with 2 equivalents of n-butyl lithium followed by quenching with dry ice to give acetylenic acid (c) in 54% yield. Treatment of (c) with excess thionyl chloride without solvent at 50 followed by addition of isobutyl amine in benzene gave the acetylenic amide (d) as a viscous oil in 96% yield. Partial reduction of (d) gave cis-fagarmide (7 ) in 89% yield. 

Our experience with tributylamine shows that its cathodic potential limit may be as low as 0 V Li/Li+. The cathodic limiting reaction may be the reduction of the cation (for alkaline metals and TAA salts). We have evidence that tributylamine reacts with lithium to form amides (RjNLi, 0 < x < 2, ldeposition potentials of the alkaline metals are reached, trialkylamine solvents will react with the deposits. The anodic limit of most of the trialkylamines, as well as of secondary amines, is in the 3.5-4 V range versus Li/Li+. The reaction is probably the formation of tetraalkyl ammonium cations, protons, and nitrogen. Hence, the electrochemical limit of amines may range between 2-4 V (higher for the tertiary amines). 

Furthermore, it seems reasonable to ascribe the regiochemistry observed to that of an unencumbered radical anion or solvent separated species in the radical anion reductions and the triethylamine photochemical runs. Various studies on lithium biphenylide have shown that it exists both as a contact ion pair and a solvent separated ion pair in THF, although at or below 20 °C mostly as a solvent separated ion pair [47,48], In the case of the exciplex between the radical anion of 1 and Et3N+, various studies of pyrene and aliphatic or aromatic amine exciplexes [49, 50] and related excited singlet states of EDA complexes... 

Unsymmetrical secondary amines are readily prepared in good yields by the catalytic reduction of Schiff bases at moderate temperatures in high-or low-pressure equipment. Many examples have been cited. The intermediate imines are prepared from primary amines and aldehydes—very seldom from ketones—and may be used without isolation (cf. method 431). For the preparation of aliphatic amines, e.g., ethyl-w-propylamine and n-butylisoamylamine, a prereduced platinum oxide catalyst is preferred with alcohol as the solvent. Schiff bases from the condensation of aromatic aldehydes with either aromatic or aliphatic amines are more readily prepared and are reduced over a nickel catalyst. In this manner, a large number of N-alkylbenzylamines having halo, hydroxyl, or methoxyl groups on the nucleus have been made. Reductions by means of sodium and alcohol and lithium aluminum hydride have also been described,... 

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