Asymmetric Rhodium-Catalyzed Hydrogenation Meets Gold-Catalyzed Cyclization: Enantioselective Synthesis of 8-Hydroxytetrahydroisoquinolines

Different furyl‐substituted (Z)‐dehydroamino acid derivatives were hydrogenated with the rhodium/Mandyphos(OMe)‐system to give enantiomeric excesses between 80 and 98 %. The absolute configuration of the newly formed stereogenic center was determined by anomalous diffraction to be R. These chiral furyl alanines were transferred into 8‐hydroxytetrahydroisoquinolines by employing gold‐catalyzed arene synthesis as the key step. During the latter reaction sequence, also including either a propargylation or a reduction, a protection of the hydroxy group, and a subsequent propargylation, no racemization of the stereogenic center was observed. With very electron‐rich furans, instead of the 8‐hydroxytetrahydroquinolines as products, furans anellated to seven‐membered rings with exocyclic CC double bonds are formed under the same reaction conditions. Homogeneous catalysis: Gold catalysis provides mild conditions for the synthesis of tetrahydroisoquinoline‐building blocks, including those containing α‐chiral ester groups, without racemization. The enantiomerically pure substrates for the gold‐catalyzed step were produced by catalytic asymmetric rhodium‐catalyzed hydrogenation (see scheme).