Transition metal catalyzed C–H functionalization of pharmaceutically relevant heterocycles

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.

CH_activtion

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

TOC_diarylethers
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
Catalysis_TOC_graphics

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

TOC_graphics

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

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

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

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