Ruthenium Catalyzed Tandem Pictet–Spengler Reaction
Anju Nalikezhathu, Valeriy Cherepakhin, Travis J. Williams
Abstract
We report a pyridyl-phosphine ruthenium(II) catalyzed tandem alcohol amination/Pictet–Spengler reaction sequence to synthesize tetrahydro-β-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.
Topics & Concepts
ChemistryAminationCatalysisTandemRutheniumAlcoholOrganic chemistryLewis acids and basesPhosphineTryptamineCascade reactionCombinatorial chemistryBiochemistryComposite materialMaterials scienceAsymmetric Hydrogenation and CatalysisSynthesis and bioactivity of alkaloidsChemical synthesis and alkaloids