Metal-ammonia reduction conditions

A useful alternative to catalytic partial hydrogenation for converting alkynes to alkenes IS reduction by a Group I metal (lithium sodium or potassium) m liquid ammonia The unique feature of metal-ammonia reduction is that it converts alkynes to trans alkenes whereas catalytic hydrogenation yields cis alkenes Thus from the same alkyne one can prepare either a cis or a trans alkene by choosing the appropriate reaction conditions... 

A remarkable feature of the Birch reduction of estradiol 3-methyl ether derivatives, as well as of other metal-ammonia reductions, is the extreme rapidity of reaction. Sodium and -butyl alcohol, a metal-alcohol combination having a comparatively slow rate of reduction, effects the reduction of estradiol 3-methyl ether to the extent of 96% in 5 minutes at —33° lithium also effects complete reduction under the same conditions as is to be expected. Shorter reaction times were not studied. At —70°, reduction with sodium occurs to the extent of 56 % in 5 minutes, although reduction with lithium is virtually complete (96%) in the same time. (The slow rates of reduction of compounds of the 5-methoxytetralin type is exemplified by 5-methoxy-tetralin itself with sodium and f-butyl alcohol reduction occurs to the extent of only 50% in 6 hours vs. 99+% with lithium.) The iron catalyzed reaction of sodium with alcohols must be very fast since it competes so well with the rapid Birch reduction. One cannot compensate for the presence of iron in a Birch reduction mixture containing sodium by adding additional metal to extend the reaction time. The iron catalyzed sodium-alcohol reaction is sufficiently rapid that the aromatic steroid still remains largely unreduced. 

The 17-ethylene ketal of androsta-l,4-diene-3,17-dione is reduced to the 17-ethylene ketal of androst-4-en-3,17-dione in about 75% yield (66% if the product is recrystallized) under the conditions of Procedure 8a (section V). However, metal-ammonia reduction probably is no longer the method of choice for converting 1,4-dien-3-ones to 4-en-3-ones or for preparing 5-en-3-ones (from 4,6-dien-3-ones). The reduction of 1,4-dien-3-ones to 4-en-3-ones appears to be effected most conveniently by hydrogenation in the presence of triphenylphosphine rhodium halide catalysts. Steroidal 5-en-3-ones are best prepared by base catalyzed deconjugation of 4-en-3-ones. ... 

In one paper, a new methodology for the remarkably selective reduction of organic molecules, possessing very negative reduction potentials, is developed. Due to the relatively simple reaction conditions, this method may be an interesting alternative to alkali metal-ammonia reductions. 

Procedures for metal-ammonia reductions have been described in several reviews and are outlined for specific substrates in later parts of this section. The following comments are therefore only a summary of the more important factors. Many reductions are relatively insensitive to the choice of conditions, but the majority may be significantly improved by the appropriate choice of metal, proton source, temperature, order of mixing and quenching procedure. 

Generally, the conditions employed in the work-up of metal-ammonia reductions leads to products having the more stable configuration at the a-carbon atom, but products having the less stable configuration at this center have been obtained by kinetic protonation of enolate intermediates.A more detailed discussion of stereochemistry in metal-ammonia reduction of a, -unsaturated carbonyl compounds is given in ref 10. 

By a suitable choice of conditions (metal hydrides or metal/ammonia) ketones at the 1-, 2-, 4-, 6-, 7-, 11-, 12- and 20-positions in 5a-H steroids can be reduced to give each of the possible epimeric alcohols in reasonable yield. Hov/ever, the 3- and 17-ketones are normally reduced to give predominantly their -(equatorial) alcohols. Use of an iridium complex as catalyst leads to a high yield of 3a-alcohol, but the 17a-ol still remains elusive by direct reduction. 

The present preparation Illustrates a general and convenient method for a two-step deoxygenation of carbonyl compounds to olefins. Related procedures comprise the basic decomposition of p-toluenesulfonylhydrazones,2 the hydride reduction of enol ethers,3 enol acetates,9 enamines,3 3 the reduction of enol phosphates (and/or enol phosphorodlamidates) by lithium metal in ethylamine (or liquid ammonia),33 the reduction of enol phosphates by titanium metal under aprotic conditions,32 the reduction of thioketals by Raney nickel,33 and the reduction of vinyl sulfides by Raney nickel in the presence of isopropylmagnesium bromide.3 ... 

Researchers have often suggested (3, 4) that methyl-ammonia reduction must be carried out with carefully purified polynuclear aromatic compounds and scrupulously dried ammonia and ethyl ether cosolvents. Hence Burkholder and I (8) were surprised to learn that commercial anthracene could be reduced almost quantitatively without prior purification of ammonia or THF (or ethyl ether) and with a rather wide variation in the amount of metal used. More recently, my co-workers and I (14) found that 0.5 g of anthracene in ammonia-THF containing 3 mL of H20 can be reduced in excellent yield by the addition of 2.5 mol of sodium (Scheme V). These results indicate that electron addition to polynuclear aromatic compounds is a very fast process, and destruction of the metal by water is simply not competitive under these conditions. 

Isolated carbon-carbon double bonds are not normally reduced by dissolving metal reducing agents. Reduction is possible when the double bond is conjugated, because the intermediate anion can be stabilized by electron delocalization. The best reagent is a solution of an alkali metal in liquid ammonia, with or without addition of an alcohol - the so-called Birch reduction conditions. Under these conditions conjugated alkenes, a,p-unsaturated ketones and even aromatic rings can be reduced to dihydro derivatives. 

The cleavage of carbon-oxygen bonds from alkenyl or aryl phosphates can be accomplished under reductive conditions with a low valent metal. As vinyl phosphates can be formed readily from ketones, this procedure provides a method to convert a ketone to an alkene. For example, the alkenyl phosphate 74 was prepared by trapping the enolate formed on reduction of the enone 73 and was converted into the alkene 75 (7.55). The chemistry therefore provides a method to prepare structurally specihc alkenes. Low-valent titanium (prepared for example by reduction of titanium(III) chloride with potassium metal) is a convenient alternative to lithium or sodium in liquid ammonia or an amine for the reductive cleavage of alkenyl or aryl phosphates. 

Dithioacetals can also be desulphurized under radical conditions using tributyltin hydride (TBTH) (equation 65) or by using metal-ammonia solutions (equation 66). Lithium aluminium hydride has also been used in some cases for reductive desulphurization. In a manner analogous to the preparation of dithioacetals, ketones can be transformed to diselenoacetals with aryl or alkyl selenol. These in turn have been reduced with Raney or Li-EtNH2 and under radical conditions with TBTH or... 

Massive metal catalysts are usually made from a mixture of both metal and promoter oxides by reduction with H2 or N2/H2 gas. Many studies of activation processes have been carried out on Fe catalysts which are written elsewhere [107]. The commercial iron catalyst needs to be reduced for a long period because it is in a massive form and the oxide is not easily reduced completely. The iron catalyst is activated under the ammonia synthesis condition [108], during which the surface structure probably changes to form the active sites [109]. On the other hand, supported precious metal catalysts such as Ru catalysts need a short reduction time because their starting compounds are easily reduced. Generally, they have no induction period with respect to the activity. 

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