Toward safer processes for C-C biaryl bond construction: catalytic direct C-H arylation and tin-free radical coupling in the synthesis of pyrazolophenanthridines.
A series of pyrazolo[1,5-f]phenanthridine derivatives has been efficiently synthesized by a short, straightforward sequence. A tandem amine-exchange/heterocyclization of enaminones was successfully applied to the regioselective preparation of 1,5-diarylpyrazole intermediates with structure resemblance to relevant nonsteroidal anti-inflammatory drugs such as celecoxib or tepoxalin. The final key step, cyclization by intramolecular biaryl bond formation, was accomplished by two alternative methodologies: radical coupling and catalytic direct arylation via C-H activation. The scope and limitations of the two methodologies have been explored and their complementariness has been established. In addition, polymer-supported heterogeneous catalysts have been compared with homogeneous analogues. In the radical process, toxic tin derivatives have been avoided in order to employ environmentally safer protocols.
Hernández
Susana
S
Kimika Organikoa II Saila, Zientzia eta Teknologia Fakultatea, Euskal Herriko Unibertsitatea, 644 P.K. 48080 Bilbao, Spain.
Moreno
Isabel
I
SanMartin
Raul
R
Gómez
Germán
G
Herrero
María Teresa
MT
Domínguez
Esther
E
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014001:Tin / Q000737:chemistry*
D000588:Amines; D005609:Free Radicals; D006571:Heterocyclic Compounds; D010617:Phenanthridines; C548180:pyrazolo(1,5-f)phenanthridine; D014001:Tin