Ethers dissolving metal reduction

Dissolving metal reductions of the benzene rings are especially important with functional derivatives of benzene such as phenols, phenol ethers and carboxylic acids (pp. 80, 82,93 and 140). 

As early as 1969, Pedersen was intrigued by the intense blue colour observed upon dissolution of small quantities of sodium or potassium metal in coordinating organic solvents in the presence of crown ethers. Indeed, the history of alkali metal (as opposed to metal cation) solution chemistry may be traced back to an 1808 entry in the notebook of Sir Humphry Davy, concerning the blue or bronze colour of potassium-liquid ammonia solutions. This blue colour is attributed to the presence of a solvated form of free electrons. It is also observed upon dissolution of sodium metal in liquid ammonia, and is a useful reagent for dissolving metal reductions , such as the selective reduction of arenes to 1,4-dienes (Birch reduction). Alkali metal solutions in the presence of crown ethers and cryptands in etheric solvents are now used extensively in this context. The full characterisation of these intriguing materials had to wait until 1983, however, when the first X-ray crystal structure of an electride salt (a cation with an electron as the counter anion) was obtained by James L. Dye and... 

The diphenylmethylene group provided an easy solution to the problem of selectively deprotecting the terminal 1,2-diol of a polyhydroxylated fragment of the antibiotic Roxaticin.183 Dissolving metal reduction of the diphenylmethylene group [Scheme 3.99] was accomplished in 96% yield with lithium in liquid ammonia without harm to three isopropyl idene groups and a rm-bu ty 1 d im ethyl si ly] ether. 

Ethers may be removed commonly by acid, with the THE derivative 1.79 reacting more rapidly than the tert-hutyl ether. Benzyl ethers may be removed under a variety of conditions such as hydrogenolysis, dissolving metal reduction (Na in NH3) and HBr (mild). Methyl ethers are cleaved by refluxing with EtSNa and DME tert-Butyl ethers can be cleaved with trifluroacetic acid (CE3COOH) at 25°C. 

The dissolving metal reductions of bicyclo[2.2. l]heptanones have been studied extensively, and it has been established that both metal-alcohol and metal-NH -proton donor systems provide the cndr>-alcohol regardless of its stability relative to the exo isomer. " - In the case of camphor (1) which has been studied in the most detail, the ratio of endo-alcohol (bomeol 2) to CAo-alcohoI (isobomeol 3) is very close to 90 10 for all metal-NH3 conditions employed. The variables include temperature (-33 and -78 °C), cosolvent (ether and THF), metal (Li, Na, K, Rb) and proton donor (NH4CI and ethanol). - The same results are obtained with both (+)- and (+)-camphor. These results are, coincidentally, almost identical to the equilibrium ratio for alcohols (2) and (3). ... 

Catalytic hydrogenation of an enone would not be chemoselective if an isolated double bond were also present in the molecule. However, isolated double bonds are inert to dissolving metal reduction. On the other hand, a variety of functional groups are reduced with alkali metals in liquid ammonia. These include alkynes, conjugated dienes, allylic, or benzylic halides and ethers. 

The enolate that is required for the aldol reaction can be generated in other ways, too. For example, trimethylsilyl enol ethers react with TBAF (tetrabutylammonium fluoride, BU4ISD F ) to give the corresponding enolates. Enolates may also be prepared by the dissolving metal reduction of a.jS-unsaturated ketones (see Chapter 5). 

One of die most popular reactions in organic chemistry is dissolving metal reductions [1-3], Two systems are frequently used - sodium dissolved in ammonia with alcohol and lithium dissolved in alkylamines [4]. Although calcium is seldom used, it has been successfully applied to the reduction of a variety of compounds and functional groups [5], including aromatic hydrocarbons, carbon-carbon double and triple bonds, benzyl ethers, allyl ethers, epoxides, esters, aliphatic nitriles, dithianes, als well as thiophenyl and sulfonyl groups. 

On a related front, the reactions of carbonyl compounds with metaliated derivatives of 2-methylthia-zoline furnish adducts (85). Although the initial nucleophilic addition occurs smoothly with a wide variety of aldehydes and ketones, the intermediate P-hydroxythiazolines (85) suffer thermal reversion upon attempted purification by distillation. Moreover, attempted cleavage of the corresponding P-hydroxythia-zolidines, which are readily produced from (85) upon dissolving metal reduction (Al-Hg), leads to the formation of p-hydroxy aldehydes only in simple systems numerous complications arising from dimerization, dehydration and retroaldol processes of the products usually intervene. Consequently it is necessary to protect the initial 1,2-adducts (85 = H) as the corresponding 0-methoxymethyl ether... 

Because enones are much more reactive towards dissolving metal reductions than nonactivated double bonds it is possible to selectively reduce the former in the presence of the latter type of double bond (Table 5, entries 1, 5 and 6). Furthermore, inverse addition of the lithium in ammonia solution to the substrate dissolved in diethyl ether allows selective reduction in the presence of other highly sensitive functional groups such as vinyl chlorides (entry 5). Under normal reaction conditions the chlorine is removed yielding the corresponding olefin49. 

The chemo-, regio-, and stereoselectivity of the ring contraction process has been demonstrated with a variety of dienol ethers obtained by dissolving metal reduction of aromatic methyl ethers (eqs 4 and 5). ... 

Epoxide cleavage which follows upon dissolving metal reduction of proximal cyclopropane rings makes possible the ready synthesis of functionalized strained ring compds. otherwise inaccessible. - E An ethereal soln. of 7,7-dimethyl-6,8-diphenyl-3-oxatetracyclo[3.3.0.02,4.06,8]octane added to anhydrous NH3 containing Li-wire, and stirred 1 hr. at -33° 5,5-dimethyl-eu /o-4,6-diphenyltri-cyclo[4.1.0.03,7]heptan-2-exo-ol. Y 90%. F. e. s. L. A. Paquette et al., J. Org. Chem. 39, 467 (1974). 

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