We recently developed a straightforward method for the synthesis of benzylic amines that involves the coupling of amines with alkylquinones. The reaction is based on alkylquinone tautomerization thereby providing a reactive quinone methide that is then trapped by the amine under mild conditions. The substrate scope of our method allows application to diverse alkylquinones as well as amines coupling partners. To further demonstrate the synthetic value of this reaction, we have applied it to the synthesis of calothrixin B, a bioactive alkaloid isolated from cyanobacteria. In our synthetic plan, we envisioned that murrayaquinone A, a readily available alkylquinone, would be a suitable substrate capable of tautomerization to the corresponding quinone methide that would undergo nucleophilic attack by aniline, or a N-protected analogue. Intramolecular cyclization by C-C bond formation would provide calothrixin B. We also explored an alternative route to calothrixin B involving initial arylation of murrayaquinone A with an ortho substituted aniline derivative followed by an intramolecular amination of the methyl group using our alkylquinone tautomerization reaction. This work establishes the utility of alkylquinone tautomerization / amination sequence for natural product synthesis.

Application of alkylquinone tautomerization to the total synthesis of Calothrixin B

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.