Birch reduction examples

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). 

Section 1111 An example of a reaction m which the ring itself reacts is the Birch reduction The ring of an arene is reduced to a nonconjugated diene by treatment with a Group I metal (usually sodium) m liquid ammonia m the presence of an alcohol... 

The following examples may be cited to illustrate these generalizations. />-Toluic acid under conditions of the Birch reduction essentially as given in this procedure yields mainly 1,2,3,4-tetrahydro-/>-toluic acid (cis and trans) plus minor amounts of... 

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 ... 

Scheme 5.10 lists some examples of the use of the Birch reduction. Entries 1 and... 

Dipyrrolo[l,2- 2, l - ]pyrazines, for example, 47, and related dipyrrolopyrimidines can be partially reduced in the central diazine ring under Birch reduction conditions to give the corresponding dihydro derivative 48 (Equation 5) <2005JOC2054>. 

The development of facial selective addition reactions of cyclohexa-1,4-dienes 7 and 14 has greatly extended the value of the asymmetric Birch reduction-alkylation. For example, amide directed hydrogenation of 15 with the Crabtree catalyst system occurs with outstanding facial selectivity iyw to the amide carbonyl group to give 16 (Scheme 5)."... 

I he procedure described is patterned after the method suggested by Vogel, Schubart, and Boll, and it illustrates a general method of preparing oxepins. Furthermore, the first step represents an example of the Birch reduction of an aromatic hydroearl )on. The second step is illustrative of the selective epoxidation of a diene system. ... 

About 6 lO " different possible isomers of CjqHjj were estimated [50]. This number, the similarity between this isomers and the instability of hydrofuUerenes make it almost impossible to get the exact structure of the isomers that are included in the complex mixture of CjqHjj isomers obtained by Birch reduction [51]. Based on H and He NMR spectroscopy and on calculations (Section 5.3.5) Cj-, Cj-, D -, Sg-isomers and a T-isomer are supposed to be among the preferred isomers [7,48, 51-53], Some examples of probable structures are given in Figure 5.10 below (Section 5.3.5). 

The general Birch reduction-alkylation procedure (ride supra) is employed. In this case A = 1. B = 2.2. C = 0 and D = 2. For specific examples, sec Table 6. 

Birch reduction-alkylation of (2S)-2-methoxymethyl-l-(2-phenylbenzoyl)pyrrolidine (1) gives products 2 in high diastereoselectivities29. In contrast to the previous examples, only one double bond remains in the product (if one equivalent of rm-butyl alcohol is used as proton donor). Formally this procedure is a stereoselective cis addition, and is thus particularly useful. Thus, two stereogenic centers are created in the same reaction step with high diastereoselectivities. Subsequent hydrolysis furnishes acids, whereas reaction with methyllithium yields chiral ketones29. 

A clever application of this reaction has recently been carried out to achieve a high yield synthesis of arene oxides and other dihydroaromatic, as well as aromatic, compounds. Fused-ring /3-lactones, such as 1-substituted 5-bromo-7-oxabicyclo[4.2.0]oct-2-en-8-ones (32) can be readily prepared by bromolactonization of 1,4-dihydrobenzoic acids (obtainable by Birch reduction of benzoic acids) (75JOC2843). After suitable transformation of substituents, mild heating of the lactone results in decarboxylation and formation of aromatic derivatives which would often be difficult to make otherwise. An example is the synthesis of the arene oxide (33) shown (78JA352, 78JA353). 

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 (5-10), where sodium directly transfers an electron to an aromatic ring. An example from this chapter is found in the bimolecular reduction of ketones (9-62), where again it is... 

Polyketides.1 Polyketides are useful as precursors to acetate-derived natural products, but they are unstable owing to a marked tendency to undergo internal condensation. A new synthesis involves ozonolysis of products of Birch reduction. An example is the synthesis of the polyketide 3 from the aromatic system 1. 

The regioselectivity of this reaction in the case of certain dienes is of interest, since it has been found that the most highly substituted double bond is preferentially attacked, for example as in the mono-epoxidation of 1,2-dimethylcyclo-hexa-1,4-diene9 (formed by the Birch reduction of o-xylene, Section 7.5, p. 1114). 

The effect of electron-withdrawing substituents on the Birch Reduction varies. For example, the reaction of benzoic acid leads to... 

An interesting example, and the one where these ideas were first applied,40 is the Birch reduction of aromatic compounds by sodium in liquid ammonia containing alcohol. These reactions seem to take place by two successive electron transfers, each followed by capture of a proton, i.e. 

Birch reduction of acid derivatives is even more productive if the first-formed enolate (as 66) is used as a nucleophile. Our example also links this chapter with the last as a Cope rearrangement is featured. A group of alkaloids including mesembrine have the bicyclic structure 89. Removing the structural nitrogen atom by standard disconnections (chapters 6 and 8) leaves the carbon skeleton 91 that does not immediately look a Birch reduction product. 

Several examples of the Birch reduction of substituted benzene derivatives are shown in the following equations. Note that substituents such as alkyl and alkoxy groups prefer to be attached to one of the carbons of the double bonds of the product, while a carboxyl group prefers to be attached to one of the singly bonded carbons. Benzene derivatives with other types of substituents are usually not employed as reactants in the Birch reduction because the substituents are not stable to the reaction conditions. 

A normal alkene is not reduced under the conditions of the Birch reduction because its pi antibonding MO is too high in energy for an electron from a sodium atom to be readily added to it. However, as shown in the following example, a carbon-carbon double bond that is conjugated with a carbonyl group is readily reduced by lithium or sodium metal in liquid ammonia solvent, without any added alcohol. 

Furopyridines have a fused structure containing both a 7t-excessive furan ring and a n-deficient pyridine ring. Interesting results were obtained during the Birch reduction of the four different furopyridines, and a mechanistic interpretation for the results was presented. An example is shown in the following scheme <02JHC335>. 

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