Lithium, in ammonia

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). 

The styrene double bond in 9(ll)-dehydroestradiol 3-methyI ether (1) or its 8-dehydro counterpart is reduced by potassium or lithium in ammonia without affecting the aromatic ring estradiol 3-methyl ether (2) is formed from both compounds. Reduction of the corresponding 17-ketones occurs with partial or complete reduction of the carbonyl group. Lithium... 

Alkynes can be reduced to yield alkenes and alkanes. Complete reduction of the triple bond over a palladium hydrogenation catalyst yields an alkane partial reduction by catalytic hydrogenation over a Lindlar catalyst yields a cis alkene. Reduction of (he alkyne with lithium in ammonia yields a trans alkene. 

When double bonds are reduced by lithium in ammonia or amines, the mechanism is similar to that of the Birch reduction (15-14). ° The reduction with trifluoro-acetic acid and EtsSiH has an ionic mechanism, with H coming in from the acid and H from the silane. In accord with this mechanism, the reaction can be applied only to those alkenes that when protonated can form a tertiary carbocation or one stabilized in some other way (e.g., by a OR substitution). It has been shown, by the detection of CIDNP, that reduction of a-methylstyrene by hydridopenta-carbonylmanganese(I) HMn(CO)5 involves free-radical addition. ... 

With the nitrogen atom well protected as the cyclic carbamate 105, all attempts to open the 1,6-anhydro ring under acidic conditions failed owing to the lability of the two allylic benzyl ethers present in the molecule. However, it was possible to debenzylate 105 with lithium in ammonia to form the new cyclic carbamate 108 and acetylation then gave 109. 

The reduction of a,/ -unsaturated ketones, e.g., 7, by lithium in ammonia is another possibility for generation of enolates19. This method has been mainly used in the preparation of enolates for stereo- and regioselective alkylations in the steroid and terpenoid fields (see... 

Section 1.1.1.3.1.1.2.1.). Similarly, the reductive ring opening of cyclopropyl ketones, e.g., 8, with lithium in ammonia affords specific enolates20,21. These enolates can, of course, be used for selective alkylation. Furthermore, enol acetates, e.g., 10, are regiospecifically obtained by nucleophilic ring opening of cyclopropyl ketones21. 

Preparation of frans -alkenes The anti addition (trans-alkenes) is achieved in the presence of an alkali metal, e.g. sodium or lithium, in ammonia at —78°C. 

A novel entry to decahydrocyclopentacyclooctene derivatives via the intramolecular photocycloaddition of fused a,/3-unsaturated y-lactones has been developed (80CC1011). Irradiation of the butenolide (153) in acetone solution gave both the fused and bridged photoadducts (154) and (155) (2-3 1). The major adduct was hydrolyzed, oxidized and esterified to afford (156). Reductive cleavage of the unsaturated keto ester (156) with lithium in ammonia afforded a five-component mixture of a,/3- and /3,y-unsaturated esters. Equilibration with 0.1M sodium methoxide in methanol converted the mixture into a single a,j8-unsaturated ester (157 Scheme 34). This annelative two-carbon ring expansion method may find application in the synthesis of ophiobolin and ceroplastol sesterterpenes. 

Sodium is quite soluble in liquid ammonia, forming a saturated solution which contains 5.7 molecules of ammonia per atom of sodium. The density of the saturated solution is 0.578 g./cc. at —33.8°C. the specific conductance is 5047, and the atomic conductance is 0.800 X 104. Considerable expansion occurs when a metal is dissolved in ammonia, and it may be pointed out that a saturated solution of lithium in ammonia is the lightest liquid known at room temperature, having a density of only 0.477 g./cc. 

Figure 7. The Wiedemann-Franz ratio for solutions of lithium in ammonia at —33° C. The Lorenz number is 2.45 X 10 8 watt it/deg.2...

Overberger, C. G., E. M. Pearce and N. Mayes Polymerization of methacry-lonitrile with lithium in ammonia. J. Polymer Sci. 34, 109 (1959). Polymerization of methacrylonitrile with lithium. J Polymer Sci. 31,217 (1958). 

Fig. 27. The magnetic susceptibility of solutions of lithium in ammonia and in methylamine. The broken and solid lines indicate the predicted concentration variations of the susceptibility, based on an electron-gas picture in which electron-electron correlations are neglected (157a, 157b).

One approach to unnatural amino acids is to use a readily available amino acid, such as L-phenyl-alanine, as the starting material. The Birch reduction of L-phenylalanine (1) was carried out with lithium in ammonia, followed by acylation of the amino group to produce compound 2, which was further esterihed to produce the cyclohexa-l,4-dienyl-L-alanine derivative 3 (Scheme 11.1). The ozonolysis step of the reaction was carried out at -78°C in a dichloromethane solution presaturated with ozone to reduce the extent of oxidation of the diene 3 to produce 4. Cyclization was then carried out by the introduction of either hydroxylamine hydrochloride to produce the isoxazol-5-ylalanine derivative 5 or phenylhydrazine to give a 1 1 mixture of (l-phenylpyrazol-3-yl)alanine derivative 6 and the (l-phenylpyrazol-2-yl)alanine derivative 7.4,5... 

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. 

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