Catalytic activation of carbon-carbon bonds in cyclopentanones.
In the chemical industry, molecules of interest are based primarily on carbon skeletons. When synthesizing such molecules, the activation of carbon-carbon single bonds (C-C bonds) in simple substrates is strategically important: it offers a way of disconnecting such inert bonds, forming more active linkages (for example, between carbon and a transition metal) and eventually producing more versatile scaffolds. The challenge in achieving such activation is the kinetic inertness of C-C bonds and the relative weakness of newly formed carbon-metal bonds. The most common tactic starts with a three- or four-membered carbon-ring system, in which strain release provides a crucial thermodynamic driving force. However, broadly useful methods that are based on catalytic activation of unstrained C-C bonds have proven elusive, because the cleavage process is much less energetically favourable. Here we report a general approach to the catalytic activation of C-C bonds in simple cyclopentanones and some cyclohexanones. The key to our success is the combination of a rhodium pre-catalyst, an N-heterocyclic carbene ligand and an amino-pyridine co-catalyst. When an aryl group is present in the C3 position of cyclopentanone, the less strained C-C bond can be activated; this is followed by activation of a carbon-hydrogen bond in the aryl group, leading to efficient synthesis of functionalized α-tetralones-a common structural motif and versatile building block in organic synthesis. Furthermore, this method can substantially enhance the efficiency of the enantioselective synthesis of some natural products of terpenoids. Density functional theory calculations reveal a mechanism involving an intriguing rhodium-bridged bicyclic intermediate.
Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, USA.|Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA.
Ying
Y
Xia
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Gang
G
Lu
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Peng
P
Liu
Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, USA.|Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA.
Guangbin
G
Dong
D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D003512:Cyclohexanones / Q000737:chemistry; D003517:Cyclopentanes / Q000737:chemistry*; D006860:Hydrogen Bonding; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry; D011789:Quantum Theory; D012238:Rhodium / Q000737:chemistry; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry; D044024:Tetralones / Q000737:chemistry
D001688:Biological Products; D003512:Cyclohexanones; D003517:Cyclopentanes; D011725:Pyridines; D013729:Terpenes; D044024:Tetralones; C007201:cyclopentanone; C030011:carbene; D002244:Carbon; D012238:Rhodium; C023666:pyridine; D008697:Methane