Transition metal catalyzed C–H functionalization of pharmaceutically relevant heterocycles

C-H functionalization, Research, Synthetic methodologies

Heterocycles are among the most frequently encountered scaffolds in drugs and pharmaceutically relevant substances. Among the plethora of available methods for their functionalization, the most appealing are those relying on a transition metals-catalyzed direct transformation of the C–H to C–C or C–Heteroatom bonds.

We have developed one-pot sequential multi-step approach to functionalization of aromatic and heterocyclic C–H bonds. The methodology comprises an initial reaction of electron-rich arenes or heteroarenes with a suitable I(III) reagent. The in situ formed unsymmetrical diaryl-λ3-iodanes subsequently undergo Cu or Pd-catalyzed reaction with wide range of oxygen and nitrogen nucleophiles.

Publications

7. Sokolovs, I.; Suna, E. “Para-Selective Cu–catalyzed C–H Aryloxylation of Electron-rich Arenes and Heteroarenes” J. Org. Chem. 2016, 81, 371–379. DOI: 10.1021/acs.joc.5b02728

Para-Selective Cu–catalyzed C–H Aryloxylation of Electron-rich Arenes and Heteroarenes

6. Berzina, B.; Sokolovs, I.; Suna, E. “Copper-Catalyzed para–Selective C–H Amination of Electron-Rich Arenes” ACS Catalysis 2015, 5, 7008–7014. DOI: 10.1021/acscatal.5b01992

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5. Sokolovs, I.; Lubriks, D.; Suna, E. “Copper-Catalyzed Intermolecular C-H Amination of (Hetero)arenes via Transient Unsymmetrical-λ3-Iodanes” J. Am. Chem. Soc. 2014136, 6920–6928. DOI: 10.1021/ja502174d.

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4. Lubriks, D.; Sokolovs, I.; Suna, E. “Indirect C–H Azidation of Heterocycles via Copper-Catalyzed Regioselective Fragmentation of Unsymmetrical λ3-Iodanes” J. Am. Chem. Soc. 2012, 134, 15436-15442.  DOI: 10.1021/ja305574k

Indirect C–H Azidation of Heterocycles via Copper-Catalyzed Regioselective Fragmentation of Unsymmetrical λ3-Iodanes

3. Suna, E. “Transition-Metal-Catalyzed Acetoxylation of Heterocycles: All that Glitters is not Palladium” (Highlight). Chem. Heterocycl. Comp. 2012, 48, 44-48. DOI: 10.1007/s10593-012-0967-5. Full Text

Transition-Metal-Catalyzed Acetoxylation of Heterocycles: All that Glitters is not Palladium

2. Lubriks, D.; Sokolovs, I.; Suna, E. “Iodonium Salts Are Key Intermediates in Pd-Catalyzed Acetoxylation of Pyrroles” Org. Lett. 2011, 13, 4324–4327. DOI: 10.1021/ol201665c

Iodonium Salts Are Key Intermediates in Pd-Catalyzed Acetoxylation of Pyrroles

1. Mutule, I.; Suna, E.; Olofsson, K.; Pelcman, B. “Catalytic Direct Acetoxylation of Indoles” J. Org. Chem. 2009, 74, 7195-7198. DOI: 10.1021/jo901321b

Catalytic Direct Acetoxylation of Indoles