Lithium, in liquid

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). 

The preparation of 17j -hydroxy-4a-methyl-5a-androstan-3-one (3) which cannot be obtained by direct alkylation or via formyl or oxalyl ketones was achieved by Schaub in 40% yield by the Stork " alkylation procedure. As discussed in the introduction this method proceeds by trapping the A -enolate (2), obtained from (1) and lithium in liquid ammonia, with methyl iodide. 

Most of the alkylations were carried out by adding a solution of 3,3-ethylenedioxypregna-5,16-dien-20-one in tetrahydrofuran to a solution of lithium in liquid ammonia to the point of color discharge. Treatment with the alkyl halide then furnishes the corresponding 17a-alkyl derivative (10). After hydrolysis of the 3-ketal group, 17a-methyl-, ethyl-, propyl-, butyl-, hexyl-, octyl-, allyl-, and benzylprogesterones are obtained. 

Catalytic reduction of thiophenes over cobalt catalysts leads to thiolane derivatives, or hydrocarbons. " Noncatalytic reductions of thiophenes by sodium or lithium in liquid ammonia leads, via the isomeric dihydrothiophenes, to complete destructions of the ring system, ultimately giving butenethiols and olefins. " Exhaustive chlorination of thiophene in the presence of iodine yields 2,2,3,4,5,5,-hexachloro-3-thiolene, Pyrolysis of thiophene at 850°C gives a... 

The product i n this case is a cis-disubstituted alkene, so the fi rst question is, " What is an immediate precursor of a cis-disubstituted alkene " We know that an alkene can be prepared from an alkyne by reduction and that the right choice of experimental conditions will allow us to prepare either a trans-disubstituted alkene (using lithium in liquid ammonia) ora cis-disubstituted alkene (using catalytic hydrogenation over the Lindlar catalyst). Thus, reduction of 2-hexyne by catalytic hydrogenation using the Lindlar catalyst should yield cis-2-hexene. 

The alkoxycarbonyl group activates the N — N bond, so that a racemization-free reductive cleavage by treatment with a large excess of lithium in liquid ammonia is possible (sec procedure below). This method is not suitable for hydrazines containing a benzylic C-N bond, because it is cleaved under the reducing conditions. 

The deep blue solution of lithium in liquid ammonia generally turned pale blue at the end of the addition, and a white precipitate of the lithium enolate and/or lithium hydroxide could be seen. 

Begin not with the ketone itself, but with an a,P-unsaturated ketone in which the double bond is present on the side where alkylation is desired. Upon treatment with lithium in liquid NH3, such a ketone is reduced to an enolate... 

Alternative conditions for reductive decyanations can be used. The allylic ether in compound 26, an intermediate in a total synthesis of (-)-roxaticin, was prone to reduction when treated with lithium in liquid ammonia. Addition of the substrate to an excess of lithium di-ferf-butylbiphenylide in THF at -78°C, and protonation of the alkyllithium intermediate provided the reduced product 27 in 63% yield, as a single diastereomer (Eq. 7). a-Alkoxylithium intermediates generated in this manner are configurationally stable at low temperature, and can serve as versatile synthons for carbon-carbon bond forming processes (see Sect. 4). 

Methylation of the ketone occurs from the loss crowded underside to give enone (36) which is reduced to saturated ketone (37) by lithium in liquid ammonia. 

For preparative purposes, titanium metal can be used in place of sodium or lithium in liquid ammonia for both the vinyl phosphate231 and aryl phosphate232 cleavages. The titanium metal is generated in situ from TiCl3 by reduction with potassium metal in tetrahydrofuran. 

Benkeser, R. A. etal., Tetrahedron Lett., 1984, 25, 2089-2092 The use of calcium in 1,2-diaminoethane as a safer substitute for sodium or lithium in liquid ammonia for the improved Birch reduction of aromatic hydrocarbons is described in detail. 

The rational synthesis of 11 started from 4,5-benzocycloheptenone ethylene ketal 16 which was reduced to the dihydrocompound 17 with lithium in liquid ammonia. Cyclopropanation of the latter with dichlorocarbene then gave the adduct 18, the ketal oxygens of 7 7 presumably coordinating with the carbene and directing it... 

An efficient synthesis of ( )-yohimbine has been published by Stork and Guthikonda (222). Reaction of the pyrrolidine enamine of A-methylpiperidone with methyl 3-oxo-4-pentenoate gave 411 in good yield. Reduction of 411 with lithium in liquid ammonia furnished trans-TV-methyldecahydroisoquinolone 412. This building block was transformed in simple reaction steps to secoyohimbane 413 from which ( )-yohimbine could be obtained by oxidative cyclization with... 

Tetraphenyltin reacts with lithium in liquid ammonia to give (Ph3Sn)3Sn Li(NH3)4+. In the crystal, the (Ph3Sn)3Sn anion has a trigonal-bipyramidal structure.482... 

The use of lithium in liquid ammonia to reduce enones is a well-known, well-established procedure which has seen widespread use. The nucleophilic character of the -carbon is clear, and has been demonstrated in many ways. For example, reduction of enone 253 leads to displacement of tosylate and formation of the tricyclic ketone 254 [68,69]. It is interesting to note that the yield for formation of 254 is a function of the nature of the reducing agent. For example, using Li/NH3, a 45% yield is obtained, while with lithium dimethylcuprate, it is 96% [70], and via cathodic reduction, 98%. 

In practice, the equivalent synthon of 2 was l-cyano-4,5-dimethoxybenzocyclobutene 22 (Scheme 3.7) which on heating generates a reactive o-quinodimethane by a conrotatory electrocyclic ring opening process (Cf. Scheme 3.7) and reacts, at 150-160 °C, with the 3,4-dihydroisoquinoleine 23 to give 80-88%yield of 13-cyanoprotoberberine 24. A simple reductive decyanation with lithium in liquid ammonia in the presence of isopropyl alcohol afforded xylopinine (19) in 84.6% yield [19]. 

At the same time, McMurry with species of Ti(0) prepared by reduction of TiCl3 with potassium or lithium in liquid ammonia, obtained excellent yields of... 

Reduction of benzaldehyde and p-alkylbenzaldehydes to the corresponding hydrocarbons was carried out by lithium in liquid ammonia and tetrahydro-furan in the presence of tert-h xiy alcohol or ammonium chloride (yields 90-94%) [775]. 

Naphthoic acid was reduced with sodium in liquid ammonia to 1,4-dihydro-1-naphthoic acid which, after heating on a steam bath with 20% sodium hydroxide for 30 minutes, isomerized to 3,4-dihydro-l-naphthoic acid (yield 63%) [399]. 2-Naphthoic acid treated with 4 equivalents of lithium in liquid ammonia and ethanol gave 69% yield of 1,2,3,4-tetrahydro-2-naphthoic acid. With 7 equivalents of lithium, l,2,3,4,5,8-hexahydro-2-naphthoic acid was obtained in 82% yield [986]. 

In an interesting reaction, -santonin was reduced with lithium in liquid ammonia so that the lactone was hydrogenolyzed to an add and one of the double bonds conjugated with the carbonyl was reduced. The other double bond as well as the keto group did not undergo reduction [1091]. 

The stereoselective reduction of meso-bis(bicyclopropylidenyl) (meso-87) with lithium in liquid ammonia gave an almost quantitative yield of the two dia-stereomeric quatercyclopropyls trans,trans-229 and cis,trans-230 in a ratio of 4.4 1 (Scheme 53) [56]. On the other hand, reduction of meso-87 with diimine generated from 2-nitrobenzenesulfonyl hydrazide gave the czs,czs-quatercyclo-propyl (231) (Fig. 6) as the main product (isolated by chromatography) along with the cz s,traz2S-diastereomer 230 (Scheme 53) [56]. 

Me. A third possibility would be that the a-chloroenolate intermediate, which is a carbenoid, would a-eliminate a chloride ion to yield carbene 229, which would subsequently intramolecularly cycloadd onto the double bond of the enone moiety. When = H, Me as in 231 a, b, reductive cleavage of the C - bond (e.g. with lithium in liquid NH3) can produce bicyclo[2.2.2]octane derivatives 230. The... 

The /3-position of an enamine system is much more difficult to meta-late than the a-position because of the higher electron density on the /3-carbon, and so additional activation, or stronger base systems, are often required for efficient reaction. Thus, successful /3-lithiation of the 3-(phenylthio)enamine of morpholine can be achieved because of the stabilizing effect of the sulfur atom, whereas reductive lithiation of the same species can be achieved with lithium napthalenide or lithium in liquid ammonia (Scheme 131) [82JCR(M)621,82JCR(S)48]. Similar /3-lithioenam-... 

Electron-transfer initiation from other radical-anions, such as those formed by reaction of sodium with nonenolizable ketones, azomthines, nitriles, azo and azoxy compounds, has also been studied. In addition to radical-anions, initiation by electron transfer has been observed when one uses certain alkali metals in liquid ammonia. Polymerizations initiated by alkali metals in liquid ammonia proceed by two different mechanisms. In some systems, such as the polymerizations of styrene and methacrylonitrile by potassium, the initiation is due to amide ion formed in the system [Overberger et al., I960]. Such polymerizations are analogous to those initiated by alkali amides. Polymerization in other systems cannot be due to amide ion. Thus, polymerization of methacrylonitrile by lithium in liquid ammonia proceeds at a much faster rate than that initiated by lithium amide in liquid ammonia [Overberger et al., 1959]. The mechanism of polymerization is considered to involve the formation of a solvated electron ... 

To arrive at racemic coriolin, Danishef sky and coworkers chose to add an acetonyl fragment to a bicyclic enedione by Diels-Alder chemistry (Scheme LXXIII) Treatment of the resulting adduct 695 sequentially with a series of conventional reagents produced the key intermediate 696. Suitable aldolization deUvered 697, the functionality in which was adjusted by deconjugation and reduction. Fiuther reduction of dPSiwith lithium in liquid ammonia and methanol followed by epoxidation afforded 699. Selective oxidation of the more accessible hydroxyl group and phenyl-sulfenylation gave 700 which experiences smooth elimination to 701 after conversion to the sulfoxide. As before, epoxidation completed the sequence. 

Indole can be reduced under Birch conditions (lithium in liquid ammonia containing a hydrogen donor, e.g. methanol) to give a 4 1 mixture... 

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