Birch reduction of benzoic acid

Apparently, 1,4-dihydrobenzoic acid has been prepared only by the Birch reduction of benzoic acid, as illustrated by the present procedure.2 3... 

FORMYL-, 41, 46 methyl ester of, 41, 47 Birch reduction of benzoic acid, 43, 22... 

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). 

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... 

Propose mechanisms for the Birch reductions of benzoic acid and anisole just shown. Show why the observed orientation of reduction is favored in each case. 

The Birch reduction of benzoic acid is the same type as that of biphenyl, and the product, with protonation successively at C-4 and C-l is the acid 7.102. In the reaction medium, it will be benzoate ion 7.101 that is being reduced. As a result of the delocalisation of the negative charge in the benzoate ion, we should probably regard the carboxylate ion more as a C- than as a Z-substituent. 

Birch reduction of benzoic acids in the presence of an alcohol (proton donor) furnishes 1,4-dihydrobenzoic acids. The carboxylate salt (-CO2 M ) formed during reduction of benzoic acid derivatives is sufficiently electron rich that it is not reduced. 

Reductive Michael reactions. The anion obtained on Birch reduction of benzoic acids undergoes Michael reactions with methyl crotonate or acrylate. 

Birch reduction of benzoic acid (Na. NHa. CiHnOH) affords 1,4-dihydroben/oic acid in yield of 89-95%."- Other examples of related reductions have been summarized. ... 

Simple Birch reduction of benzoic acid 131 gives initially an intermediate that can be represented as dianion 132. Proton transfer from C02H to the less stable of the two anions gives the enolate 133 that you will recognise as a (doubly) extended enolate with one a- and two y-positions. Alkylation occurs at the a-position to give 134. This is a useful way to construct a quaternary centre on a six-membered ring the two remaining alkenes can be further developed in many ways.36... 

Although some cyclohexadienes are readily available, many can be obtained easily by Birch reduction, which involves reduction with solutions of alkali metals in liquid ammonia, a source of solvated electrons, in the presence of alcohol as a proton source.8-10 In previous years, the Bouveault-Blanc procedure, which uses sodium metal and alcohol in liquid ammonia, was frequently employed for direct reduction of aromatic esters however, it gave rise mainly to the corresponding substituted benzoic acid.11 Rabideau et al. reported a modified procedure 12 however, in our hands, this resulted in the reduction of the ester function to give benzoic acid. We have found that the Birch reduction of benzoic acid, followed by esterification, is an efficient procedure for the preparation of the corresponding 1,4-dihydro compound prior to the coordination of the arene to produce functionalized dimeric ruthenium-arene complexes.13... 

As outlined in Scheme 6, isovanillin (35) was converted to aryl iodide 36 via MOM-protection, protection of the aldehyde, and subsequent iodination. Hydrolysis of the acetal and Wittig olefination delivered phenol 37 after exposure of the intermediate aldehyde to methanolic hydrochloric acid. Epoxide 41, the coupling partner of phenol 37 in the key Tsuji-Trost-reaction, was synthesized from benzoic acid following a procedure developed by Fukuyama for the synthesis of strychnine [62]. Birch reduction of benzoic acid with subsequent isomerization of one double bond into conjugation was followed by esterification and bromohydrin formation (40). The ester was reduced and the bromohydrin was treated with base to provide the epoxide. Silylation concluded the preparation of epoxide 41, the coupling partner for iodide 37, and both fragments were reacted in the presence of palladium to attain iodide 38. 

Birch reductions of alkyl benzoates are not normally feasible due to the preference for Bouveault-Blanc-type reduction of the ester group. However, it has now been found that if one to two equivalents of water are added to the ammonia before addition of the metal, then good yields of cyclohexadiene-esters [e.g. (191) from ethyl benzoate] can be realised. It is known that Birch reductions of benzoic acids can be used to generate dianonic species (192). These have been found to undergo conjugate additions to methyl acrylate and... 

A structural requirement for the asymmetric Birch reduction-alkylation is that a substituent must be present at C(2) of the benzoyl moiety to desymmetrize the developing cyclohexa-1,4-diene ring (Scheme 4). However, for certain synthetic applications, it would be desirable to utilize benzoic acid itself. The chemistry of chiral benzamide 12 (X = SiMes) was investigated to provide access to non-racemic 4,4-disubstituted cyclohex-2-en-l-ones 33 (Scheme 8). 9 Alkylation of the enolate obtained from the Birch reduction of 12 (X = SiMes) gave cyclohexa-1,4-dienes 32a-d with diastereoselectivities greater than 100 1 These dienes were efficiently converted in three steps to the chiral cyclohexenones 33a-d. 

The Birch reduction of 3,4,5-trimethoxybenzoic add 17a b (cognate preparation in Expt 7.19) is of interest in that the product is 1,4-dihydro-3,5-dimethoxy-benzoic add (46) thus revealing that in this reduction the 4-methoxy group is removed by hydrogenolysis. The product possesses two methyl vinyl ether residues which are labile under aqueous acidic conditions to yield the saturated diketone, 3,5-diketocyclohexanecarboxylic add (47). 

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

Formation of Chiral Quaternary Carbon. Birch reduction-alkylation of benzoic acids and esters establishes quaternary carbon centers. Neighboring stereocenters will influence the stereochemical outcome of the tandem reaction sequence. The following example illustrates how a chiral auxiliary (derived from prolinol) controls the stereoselection in the Birch reduction-alkylation step. ... 

Schultz AG, Pettus L. Desymmetrization of benzoic acid in the context of the asymmetric birch reduction-alkylation protocol. Asymmetric total syntheses of (—)-ebumamonine and (—)-aspidospermidine. J. Org. Chem. 1997 62 (20) 6855-6861. 

As was mentioned in section 2.3.3, ytterbium metal dissolves in liquid ammonia to yield ammoniated electrons and Yb " ions. This solution was used by White et al. (1978) to perform reductions of various aromatic systems, similar to the Birch reactions which use lithium or sodium as the metal. The addition of benzoic acid or anisole dissolved in a 10 1 mixture of THF-tert-butyl alcohol, to an ytterbium-ammonia solution gives 1,4-dihydrobenzoic acid (56% yield). Triple bonds are cleanly reduced to trans olefins (i.e. PhC CPh traK5-PhCH=CHPh 75%). The C=C double bonds of conjugated ketones are also reduced by this system. Since the reaction medium initially contains both solvated electrons and Yb + ions it is likely that the above reactions are not directly connected with the presence of divalent ytterbium species. 

Synthetic applications of the asymmetric Birch reduction and reduction-alkylation are reported. Synthetically useful chiral Intermediates have been obtained from chiral 2-alkoxy-, 2-alkyl-, 2-aryl- and 2-trialkylsllyl-benzamides I and the pyrrolobenzodlazeplne-5,ll-diones II. The availability of a wide range of substituents on the precursor benzoic acid derivative, the uniformly high degree of dlastereoselection in the chiral enolate alkylation step, and the opportunity for further development of stereogenic centers by way of olefin addition reactions make this method unusually versatile for the asymmetric synthesis of natural products and related materials. 

The first asymmetric total synthesis of (+)-lycorine is outlined in Scheme 15. While our earlier applications of the Birch reduction-alkylation of chiral benzamide 5 were focused on target structures with a quaternary stereocenter derived from C(l) of the starting benzoic acid derivative, the synthesis of 64 demonstrates that the method also is applicable to the construction of chiral six-membered rings containing only tertiary and trigonal carbon atoms. s... 

Enantioselective Birch reduction-alkylation The chiral benzoic acid derivative 1, prepared by condensation of o-hydroxybenzoic acid with L-prolinol followed by cyclization (Mitsunobu reaction), undergoes Birch reduction (K, NH3, THF, t-butyl alcohol) followed by alkylation with C2H5I to give essentially only 2. Acid hydrolysis returns the chiral auxiliary and provides the 2-alkylated cyclo-hexenone 3. 

There is no standard, universal, procedure for the Birch reduction. Experiment 7.19 illustrates some of the variants which have been reported in the literature. The original Birch procedure is to add small pieces of sodium metal to a solution of the aromatic compound in a mixture of liquid ammonia and the proton source (ethanol).18 After completion of the reaction, which is usually indicated by the disappearance of the blue colour, it is quenched by the addition of ammonium chloride and the ammonia allowed to evaporate before the cautious addition of water, and isolation of the product by ether extraction. In a modified procedure a co-solvent (ether, tetrahydrofuran, etc.) is initially added to the solution of aromatic compound/liquid ammonia prior to the addition of metal lithium metal is often used in place of sodium.19a,b In general these latter procedures are used for substrates which are more difficult to reduce. Redistilled liquid ammonia is found to be beneficial since the common contaminant iron, in collodial form or in the form of its salts, has a deleterious effect on the reaction.20 A representative selection of procedures is given in Expt 7.19 for the reduction of o-xylene, anisole, benzoic acid, and 3,4,5-trimethoxybenzoic acid. 

Oxidative decarboxyiation of dihydroaromatic acids. Some years ago Birch mentioned that 1-substituted 1,4-dihydrobenzoic acids are decarboxylated to arenes by LTA. The starting materials are readily available by a one-step Birch reduction (Li-NHo) and alkylation from benzoic acids. Birch and Slobbe have now extended the early work and shown that this process is useful synthetically. One example is the synthesis of olivetol dimethyl ether (equation I), liquation II formulates the synthesis of a useful intermediate to dihydrojasmone. 

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