Rhodium-Catalyzed Enantioselective Intramolecular Hydroacylation of Trisubstituted Alkenes

• Published in: Chemistry : a European journal Vol. 22; no. 44; pp. 15619 - 15623
• Main Authors: Johnson, Kirsten F., Schneider, Eugene A., Schumacher, Brian P., Ellern, Arkady, Scanlon, Joseph D., Stanley, Levi M.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 24.10.2016; Wiley; Wiley Subscription Services, Inc
• Subjects: Alkenes; Architecture; asymmetric catalysis; Catalysis; Chemistry; Chemistry, Multidisciplinary; hydroacylation; Ketones; Pathways; Physical Sciences; Rhodium; Science & Technology; CHIRAL LIGANDS; NITROGEN-HETEROCYCLES; SIGMA-COMPLEX; asymmetric catalysis; alkenes; OXIDATIVE ADDITION; ASYMMETRIC CYCLIZATION REACTIONS; CYCLOPENTANONES; H BOND ACTIVATION; 4-PENTENALS; INTERMOLECULAR HYDROACYLATION; hydroacylation; HOMOGENEOUS CATALYSIS; rhodium
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201603880

We report the first examples of transition metal‐catalyzed enantioselective alkene hydroacylations with 1,1,2‐trisubstituted alkenes. DFT and mechanistic studies are consistent with a reaction pathway for these rhodium‐catalyzed processes including intramolecular alkene hydroacylation and α‐epimerization to generate highly enantioenriched, polycyclic architectures. This reaction sequence enables the hydroacylation of 2‐(cyclohex‐1‐en‐1‐yl)benzaldehydes to form hexahydro‐9H‐fluoren‐9‐ones in moderate to high yields (68–91 %) with high enantioselectivities (up to 99 % ee) and diastereoselectivities (typically >20:1). The first “tri”: The first examples of transition metal‐catalyzed, enantioselective hydroacylations of trisubstituted alkenes are reported. DFT studies are consistent with a sequence of intramolecular alkene hydroacylation and α‐epimerization to generate the polycylic ketone products with moderate‐to‐high yields and high enantioselectivities (up to 99 % ee).