Birch reduction limitations

It was realized that the mechanism of Birch reduction involves protonation of the anion-radical formed by the addition of one electron to the reacting aromatic compound. This is followed by rapid addition of a second electron and protonation of the forming carbanion to yield nonconjugated alicyclic products. Protonation of the anion-radical by added alcohol is the rate-limiting stage. Recent calculations show that the ortho and meta positions in anisole are most enhanced in density by electron introduction. The para position is not appreciably affected (Zimmerman and Alabugin 2001 Scheme 7.9). 

In contrast to the ester enolates, the a.O-carboxylic dianions are intrinsically more reactive and their use in conjugate reactions is thus limited. Typically, a-substituted-a.O-carboxylic dianions add exclusively to a,(3-unsaturated esters155a and nitroalkenes,155b while additions to ot,(3-enones are sensitive to the substitution pattern of the enones.155c>d Notable is the conjugate addition of dihydrobenzoic acid dianions (207), from Birch reduction of benzoic acids, to oi,3-unsaturated esters (Scheme 77).155e... 

Table 11 shows some representative results from the cathodic reduction of some aromatic hydrocarbons. These include cases with Ei j2 near the cathodic limit or in the discharge region of the SSE (benzene, toluene) and cases with Ex j2 at considerably more positive potential (naphthalene, anthracene again we must anticipate the discussion of reactivity and refer to Table 21). Reactions nos. 1, 2, 6, and 7 immediately demonstrate one difficulty with such studies in that the catholyte of a divided cell becomes strongly basic as electrolysis progresses. In sufficiently basic medium, the initial product, a 1,4-dihydro derivative (cf. the Birch reduction Birch and Subba Rao, 1972), will rearrange to a conjugated system which, in contrast to the 1,4-dihydro derivative, is further reducible to the tetrahydro product (nos. 1 and 6). In a non-divided cell the acid production at the anode balances the base production and thus only a little rearrangement occurs. It is therefore not a trivial problem to find out if the tetrahydro product is formed from the conjugated dihydro product, formed directly or by rearrangement [eqn (78)].

The Birch reduction of aromatic hydrocarbons and ethers to the 2,5-dihydro derivatives proceeds most satisfactorily when the substitution pattern allows the addition of hydrogen to two unsubstituted positions in a para relationship. If this requirement is satisfied, better yields are obtained from more highly substituted aromatic rings than from (say) anisole itself, which affords a substantial amount (20%) of 1-methoxycyclohexene (c/. Scheme 1). Extra substitution presumably hinders protonation at the terminus of the dienyl anion (which would lead to a conjugated diene and overreduction). The utilization of anisole moieties as precursors to cyclohexenones has been of very limited value with many 1,2,3-substitution patterns and more densely substituted derivatives. Compounds (23) to (26), for example, have only been reduced by employing massive excesses (200-600 equiv.) of lithium metal,2 while the aromatic ring in (28) is completely resistant to reduction. ... 

The opening of 9a jlOce -oxides by Grignard reagents (Scheme 74) and the Michael reaction with 17a-ketones (Schemes 104 and 105) have been used to an extremely limited extent. The passage from estrogens to 10-methylsteroids has been effected in low yield by Birch reduction and subsequent reaction with carbenes (Scheme 39). The Reimer—Tiemann reaction has been used for the same purpose [53] with the reaction (70) (71)... 

The use of mercury is - in principle -forbidden on the bench for environmental reasons. It is a pity, because mercury permits one to reach very high reducing potentials (—3 V versus the saturated calomel electrode (SCE), which is about what is necessary to achieve the reduction of benzene under conditions near to the Birch reaction). Substitute materials can be glassy carbon and graphite. Platinum and gold plates or mosses are of interest but their use is limited (because of the occurrence of hydrogen evolution) in acidic or aqueous solvents. 

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