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.
Hashmi
A Stephen K
AS
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany. hashmi@hashimi.de
Haufe
Patrick
P
Schmid
Christoph
C
Rivas Nass
Andreas
A
Frey
Wolfgang
W