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Birch reductive alkylation of biaryls: scope and limitations

Birch reductive alkylation of biaryls: scope and limitations

Journal of Organic Chemistry 74(17): 6469-6478

Birch reductive alkylation of biaryls has been carried out by varying the nature of the substituents on the aromatic rings. Our investigations have focused on electron-rich substituents such as OMe, OH, and NR(2) groups as they are present on the skeleton of targeted alkaloids. The regioselectivity is strongly affected by the electronic nature of these substituents on both rings. The 3,5-dimethoxyphenyl moiety is selectively reduced and then alkylated, while phenols and anilines do not react under these conditions. A biaryl possessing both a 3,5-dimethoxyphenyl moiety and a phenol ring may, however, be reduced and alkylated provided the acidic phenolic proton is removed prior to the treatment with Li in NH(3). Similarly, biaryls possessing a o-sulfonamide group are reduced regioselectively and alkylated with alpha-chloroacetonitrile or N-tosylaziridine to provide the corresponding dienes in reasonable to good yields. A survey of the alkylating agents was also performed showing that various functional groups may be introduced at the benzylic position, including esters, primary and tertiary amides, nitriles, epoxides, and acetals and also unfunctionalized sterically hindered t-Bu groups and cyclopropyl substituents. The introduction of the latter indicates that both a S(N)2 and a SET mechanism may take place during the alkylating step.

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Accession: 051823818

Download citation: RISBibTeXText

PMID: 19655764

DOI: 10.1021/jo901395m

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