Ruthenium Catalyzed Tandem Pictet–Spengler Reaction

Organic Letters
2020.0

Abstract

We report a pyridyl-phosphine ruthenium(II) catalyzed tandem alcohol amination/Pictet-Spengler reaction sequence to synthesize tetrahydro-beta-carbolines from an alcohol and tryptamine. Our conditions use a Lewis acid cocatalyst, In(OTf)(3), that is compatible with typically base catalyzed amination and an acid catalyzed Pictet-Spengler cyclization. This method proceeds well with benzylic alcohols, heterocyclic carbinols, and aliphatic alcohols. We also show how combining this reaction with a subsequent cycloamination enables a direct synthesis of tetracyclic alkaloids like harmicine.

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