Aromatic carboxylic Birch reduction

Reaction No. 5 (Table 11) is part of a synthetically useful method for the alkylation of aromatic compounds. At first the aromatic carboxylic acid is reductively alkylated by way of a Birch reduction in the presence of alkyl halides, this is then followed by an eliminative decarboxylation. In reaction No. 9 decarboxylation occurs probably by oxidation at the nitrogen to the radical cation that undergoes decarboxylation (see... 

Alkylation of the enolate of a carboxylic acid, formed as an intermediate in the Birch reduction of an aromatic acid, has been successfully exploited in synthesis, e.g., in the synthesis of gibberellic acid. A model compound 24 was reduced with sodium in diethyl ether-liquid ammonia and the resulting carbanion was alkylated with iodomethane to give 25 in ca. 80% yield87. 

Toledano, J. C., Olivella, S. HMO interpretation of the Birch reduction mechanism of aromatic carboxylates. Anales de Quimica, Serie C Quimica Organica y Bioquimica 1982, 78, 187-189. 

Carboxylic acids can be transformed into alkenes when they contain a leaving group like H (Scheme 12), SiMea, SPh or CO2H in the -position. The alkene is formed by an 1-elimination from the intermediate carbocation. Some examples are summarized in Table 10. The decarboxylative elimination of l,4-cyclohexadiene-6-carboxylic acids (Table 10, entry 2) is part of a useful method for the alkylation of aromatic compounds. This involves first a reductive alkylation using a Birch reduction, which is then fol-... 

As to the applications of proline, it can modify the surface of palladium on charcoal to give an enantioselective hydrogenation catalyst (Section D.2.3.1.). Forming amides with aromatic carboxylic acids, proline has served as an auxiliary in the enantioselective Birch reduction of the aromatic system (Section D. 1.1.1.3.1.). An interesting application is the catalysis of the aldol-type cyclization of triketones. Among the amino acids tested, it is often the best choice for high enantiomeric excess3 4. 

An achiral ketone (S OS) was used to prepare protected alcohol 5.206 via condensation with S-phenethylamine, and that protecting group was also an auxiliary Removal of the benzylic group and re-protection with Boc allowed Birch reduction s of the aromatic ring to give 5.207. Ozonolysis in methanol led to methyl 4-(N-Boc amino)-6-methyl-3-oxoheptanoate, 5208. In this synthesis, the phenyl ring functioned as the carboxyl surrogate and asymmetric induction in 5.208 arose from the chiral auxiliary introduced earlier in the sequence. 

The route commenced with the condensation of amine 229 and carboxylic acid 230 at 200 °C. Subsequent Bischler-Napieralski reaction and sodium borohydride reduction established the C/D ring system of morphine and delivered tetrahydroisoquinoline 231 in good yield. Next, Birch reduction and Af-formylation afforded enol ether 232, which was converted into the corresponding ketal before reaction with bromine allowed the isolation of the cyclization precursor. The halide in 233 serves to protect the para position in the aromatic ring in the subsequent acid-mediated electrophilic cyclization reaction—a common strategy that has also been applied by other research groups in their endeavors toward morphine and related alkaloids. 

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