Amines Birch reduction

Reactions in liquid ammonia have also served in the synthesis of amines. Birch reduction-alkylation of the chiral heterocycle (1),... 

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). 

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

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. ... 

Direct Electron Transfer. We have already met some reactions in which the reduction is a direct gain of electrons or the oxidation a direct loss of them. An example is the Birch reduction (15-14), where sodium directly transfers an electron to an aromatic ring. An example from this chapter is found in the bimolecular reduction of ketones (19-55), where again it is a metal that supplies the electrons. This kind of mechanism is found largely in three types of reaction, (a) the oxidation or reduction of a free radical (oxidation to a positive or reduction to a negative ion), (b) the oxidation of a negative ion or the reduction of a positive ion to a comparatively stable free radical, and (c) electrolytic oxidations or reductions (an example is the Kolbe reaction, 14-36). An important example of (b) is oxidation of amines and phenolate ions ... 

Enamines also react with diketene to form chromones (60JCS26). One drawback to this method is the use of 2,3-dihydro-Ar,Ar-dimethyl-p-toluidine, prepared by Birch reduction of the aromatic amine, and the consequent need to aromatize the reduced chromone which is the initial product. 

However, benzene and its derivatives can be reduced to cyclohexa-dienes by solutions of metals such as Li, Na, K, Zn, and Hg in a weakly acidic solvent, such as liquid ammonia, amines, or ether-alcohol mixtures. This general type of reaction is known as the Birch reduction after the Australian chemist, A. J. Birch. With benzene, reduction with metals leads to 1,4-cyclo-hexadiene ... 

A desymmetrization of cyclohexa-2,5-dienes (22) and (24), obtained by Birch reductive alkylation, through a diastereoselective intramolecular hydroamination led with high selectivity to the corresponding bicyclic allylic amines (23) and (25) (Scheme 6).19... 

R. Taylor. We tried the Birch reduction and obtained amino peaks in the ir because amination occurs under the reaction conditions. We tried to get over this problem by hydrogenating over platinum at low pressure, initially in hexane and then in benzene. Benzene must be redistilled first because it contains di-octyl phthalate. Having adopted this precaution, a purple solution was obtained which became bright yellow after 2-3 days. Of course benzene is reduced as well to cyclohexane. Another problem arises because the (hydrogenated) product, although initially soluble in... 

This is a radical reaction similar to the Birch reduction (see p. 148). In general benzyl groups are removed hydrogenolytically (see p. 260), but under these conditions elimination of the remaining double bond would occur. In the second step the carbonate is cleaved and the amine is deprotected to get the unprotected oligosaccharide 19. 

The synthesis of the tetracyclic intermediate 49 was therefore studied in the hope that it might further cyclize to the desired lycorine skeleton. Birch reduction of o,p-dimethoxyphenethylamine led to the amine 50 which was converted into 51, giving rise in turn upon hydrolysis to 49. Its structure rests on physical data. Ordinary methods for nitro group reduction seemed to also destroy the 289-nm chromophore, but hydrogen transfer (a-phellandrene and Pd/C) gave a product which analyzed for the product of nitro reduction to amine in 49, the mass spectrometric data also being in agreement. The product was, however, not affected by diazotization, and, on the basis of spectral data, was... 

The amine 74 certainly looks like a product of Birch reduction of the simple para-disubstituted benzene 76 via the enol ether 75. 

It turned out that the Birch reduction of 76 R=Me had already been done in 1958 by the standard sodium in liquid ammonia procedure but gave a low yield ( 20%) of the conjugated ketone as the first compound isolated.14 Guillou and her team improved on this by using lithium and r-BuOH at low temperature to give 78 in nearly quantitative yield.15 The reductive amination needed only NaBH4 in MeOH at room temperature and gave 78% of the enol ether of 73 from which the synthesis of 72 was completed. 

The Birch reduction has been applied to electron-deficient pyrroles substituted with a chiral auxiliary at the C(2)-position <1999TL435>. Using either (—)-8-phenylmenthol or (- -)-/ra /-2-(ot-cumyl)cyclohexanol as auxiliaries, high levels of stereoselectivity were obtained. Pyrrole 911, prepared from the l/7-pyrrole-2-carboxylic acid 910 in 90% yield, was reduced under modified Birch conditions (Scheme 176). The best conditions involved lithium metal (3 equiv), liquid ammonia and THE at —78°C. The addition of A, A -bis(2-methoxyethyl)amine (10 equiv) helped to reduce side reactions caused by the lithium amide formed in the reaction <1998TL3075>. After 15 min, the Birch reductions were quenched with a range of electrophiles and in each case 3,4-dehydroproline derivatives 912 were formed in excellent yields and with good diastereoselectivities. 

Kaiser has published a review which discusses the similarities and differences between reductions by the Birch procedure and by lithium in low molecular weight amines (Benkeser reduction). He concludes that the Benkeser reduction is more powerful but less selective than the Birch reduction. 

The metal-NH3 and metal-amine reductions of acetophenone and acetyl derivatives of polycyclic aromatics are complex and afford primarily mixtures of Birch reduction products. In some cases a ketonic carbonyl survives the reduction, and in some cases it is reduced to the corresponding alcohol. ... 

Benzylic amines are resistant to hydrogenolysis under Birch reduction conditions, unless the amine is quaternary, as in the Emde reaction. A means of preserving an aryl carbonyl group is therefore to protect it as an aminal derivative. An illustration is provided by the preparation of aldehyde (213), an important flavor constituent of cumin, as outlined in Scheme 47." ... 

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