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The partial reduction of electron-deficient pyrroles: procedures describing both Birch (Li/NH3) and ammonia-free (Li/DBB) conditions

Abstract

The partial reduction of electron-deficient pyrroles using either Birch (Li/NH3) or ammonia-free (Li/di-tert-butyl biphenyl) conditions allows formation of pyrroline compounds in good yield and, when combined with a reductive alkylation or similar approach, leads to highly functionalized, synthetically useful compounds. This methodology has been proven in the syntheses of several complex natural products, all of which show interesting biological activity. This protocol describes in detail the following stages of the partial reduction procedure: formation of the reducing solution, partial reduction of the pyrrole compound and finally quench of the resulting anion/dianion using either protonating agents or an aldehyde. The ammonia-free conditions described herein are particularly useful for reactions requiring the use of reactive electrophiles, such as acid chlorides or enolizable aldehydes, which are incompatible with the standard Birch reduction conditions. The reaction procedure for the ammonia Birch reduction (procedure A) takes about 9.5 h to complete. Those described for the ammonia-free reductions, procedure B and procedure C, can be expected to take approximately 33 and 8 h, respectively.

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Donohoe, T., Thomas, R. The partial reduction of electron-deficient pyrroles: procedures describing both Birch (Li/NH3) and ammonia-free (Li/DBB) conditions. Nat Protoc 2, 1888–1895 (2007). https://doi.org/10.1038/nprot.2007.245

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