Reduction with lithium/liquid ammonia

Yoneda, R., Osaki, H., Harusawa, S., and Kurihara, T., Reductive deoxygenation of a,P-unsatured ketones via cyanophosphates by lithium in liquid ammonia, Chem. Pharm. Bull., 37, 2817, 1989. Yoneda. R.. Osaki, T., Harusawa, S., and Kurihara, T., Dephosphorylation of cyano diethyl phosphates by reduction with lithium-liquid ammonia. An efficient method for conversion of carbonyl compounds into nitriles.. 1. Chem. Soc.. Perkin Trans. 1, 607, 1990. 

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). 

A good example is the reduction of 11-keto steroids (69) which gives only the llJ -hydroxy derivatives (70) with metal deuterides. Generally, the 1 la-alcohols are obtained in good yield by reduction with lithium in liquid ammonia-methanol mixtures. By analogy, llj -dj-lla-alcohols (71) are expected when a deuterioammonia-methanol-OD system is used. (For an alternate preparation of an 11/5-dj-l la-hydroxy steroid, see section III-C). 

Double bonds conjugated with benzene rings are reduced electrolytically [344] (p. 23). Where applicable, stereochemistry can be influenced by using either catalytic hydrogenation or dissolving metal reduction [401] (p. 24). Indene was converted to indane by sodium in liquid ammonia in 85% yield [402] and acenaphthylene to acenaphthene in 85% yield by reduction with lithium aluminum hydride in carbitol at 100° [403], Since the benzene ring is not inert toward alkali metals, nuclear reduction may accompany reduction of the double bond. Styrene treated with lithium in methylamine afforded 25% of 1-ethylcyclohexene and 18% of ethylcyclohexane [404]. 

The superfluous bromine is then removed by reduction with zinc in acetic acid (26-1). The 20 ketone is next protected against the strongly reducing conditions in the subsequent step by conversion to the ethylene glycol acetal (26-2). Birch reduction with lithium in liquid ammonia in the presence of ethanol proceeds as usual to the dihydrobenzene (26-3). Treatment of this last product with mineral acid serves to hydrolyze both the enol ether at the 3 position and the acetal at the... 

Bicyclo[4.2.0]octanes wiLh carbonyl groups adjacent to each bridgehead carbon cleave the central bond on reduction with lithium in liquid ammonia,158,159 with sodium/potassium alloy in the presence of chlorotrimethylsilane,160 with zinc in acetic acid,37 or with zinc amalgam in hydrochloric acid.15 7... 

Ring opening is common in the alkali metal and liquid ammonia reduction of furans unless an anion stabilizing group is present, so most work has been done with derivatives of furancarboxylic acids. Treatment of furan-2-carboxylic acid with lithium and ammonia at -78 °C followed by rapid addition of ammonium chloride affords 2,5-dihydrofuran-2-carboxylic acid (80%). Reductive alkylation similarly gives 2-alkyl-2,5-dihydrofuran-2-carboxylic acids. This method has been used in a synthesis of rosefuran, the intermediate dihydrofuran (66) being converted into the product (67) by oxidative decarboxylation with... 

The two free hydroxy groups are First protected with acetic anhydride. In a second step the acetyl group is reductively cleaved by a Birch reduction with lithium in liquid ammonia.19 Lithium dissolves in the ammonia with the formation of solvated electrons. Stepwise electron transfer to the aromatic species (a SET process) leads first to a radical anion, which stabilizes itself as benzylic radical 38 with loss of the oxygen substituent. A second SET process generates a benzylic anion, which is neutralized with ammonium chloride acting as a proton source (see Chapter 12). 

Catalytic hydrogenolysis using Pd—C, Pd(OH)2 or Pd(OAc)2 is the most commonly employed method for the removal of benzyl ethers, and yields are often quantitative. Cyclohexene, cyclohexadiene, formic acid and ammonium formate can also be used as hydrogen sources rather than hydrogen. Benzyl ethers can also be removed by Birch reduction with lithium or sodium dissolved in liquid ammonia, but this procedure is not often applied in carbohydrate chemistry. 

The use of 1,1-diiodomethane as an electrophile in the Birch reduction (with lithium in liquid ammonia) of electron-deficient pyrroles 915 furnished pyrrolines 916 (in high to excellent yields), which provided access to the synthetically important functionalized 5,6-dihydro-2(l//)-pyridinones 917 (via radical ring expansion), substructures commonly found in biologically active natural products (Scheme 177) <2004CC1422>. 2-(Chloroalkyl)-substituted pyrrolines 919 were duly prepared by the reductive alkylation (with l-chloro-3-iodopropane or 1-chloro -iodobu-tane) of electron-deficient pyrrole 918. Allylic oxidation then furnished lactams 920 (Scheme 178). 

Deoxygenation of phenols. The reduction of enol phosphates to alkenes by titanium metal (8,482) has been extended to reduction of aryl diethyl phosphates to arenes. Yields are in the range 75-95% reduction with lithium in liquid ammonia (1, 248) usually proceeds in low yield. 

Benzylic and allylic tertiary amines may be reduced to hydrocarbons using one of two methods. Oxidation to an amine oxide followed by reduction with lithium in liquid ammonia provides one of these... 

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). 

Sinclair, S., Jorgensen, W. L. Computer Assisted Mechanistic Evaluation of Organic Reactions. 23. Dissolving Metal Reductions with Lithium in Liquid Ammonia Including the Birch Reduction. J. Org. Chem. 1994, 59, 762-772. 

Table 12. Alkylation of Oxoterpenes by Cyclopropanation, Followed by Reduction with Lithium in Liquid Ammonia ...

Reduction of amines. Birch13 noted that N,N-dimethylaniIines are reducible by lithium and liquid ammonia, but Stork and White14 made the more significant observation that the primary amine precursors of the tertiary amines are also reducible in satisfactory yields. In a careful study of the reduction of o-toluidine. the highest yields were obtained with the combination lithium-liquid ammonia-/-butanol. One advantage of using an amine as substrate is that the unreduced basic amine is readily separated from neutral ketonic products. In all cases examined the desired unsatura-... 

The Birch reduction with alkali metals in liquid ammonia has been described for Cso already in 1990, just shortly after its isolation. A mixture of highly hydrogenated fullerene compounds QqHj, (18 < x < 36) is generated especially with lithium in ammonia in the presence of tert-butanol. Again C >Hi8 and CgoHsg are the major products. Derivatives with even more hydrogen attached carmot be obtained by Birch reduction as they decompose at the conditions applied. 

X = H2) with hydrobromic acid followed by esterification of the resulting diphenol with diethyl phosphite gave an intermediate diester which, upon lithium-liquid ammonia reduction, provided the trans-base (15 R = — H, X = H2). 

Tetraphenylcyclobutadieneiron tricarbonyl (XIII) on reduction with lithium aluminum hydride gave 1,2,3,4-tetraphenylbutadiene (52) [formerly thought to be the trans,trans isomer but now established as the cis,cis (LXI) (43)], while a sodium in liquid ammonia reduction gave 1,2,3,4-tetraphenyl-butane (52). 

---