Asymmetric synthesis of an axially chiral antimitotic biaryl via an atropo-enantioselective Suzuki cross-coupling.
A catalytic asymmetric synthesis of the axially chiral bridged biaryl (-)-2, a structural analogue of natural (-)-rhazinilam possessing original antimitotic properties, is described. The key step is an intermolecular asymmetric Suzuki coupling, furnishing the nonbridged biaryl (-)-6, precursor of (-)-2, with up to 40% ee using binaphthyl ligand 7a. Various known or new binaphthyl and ferrocenyl phosphines as well as phosphetanes were screened as ligands in this reaction, the conditions of which were optimized. The comparison with another Suzuki coupling system showed that 7a is the most versatile ligand described to date for this type of transformation. This work gives the first application of the asymmetric Suzuki coupling to a biologically relevant target.
Herrbach
Audrey
A
Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Marinetti
Angela
A
Baudoin
Olivier
O
Guénard
Daniel
D
Guéritte
Françoise
F
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D029062:Apocynaceae / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007202:Indicators and Reagents; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D009281:Naphthalenes / Q000032:analysis / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D007212:Indolizines; D007769:Lactams; D008024:Ligands; D009281:Naphthalenes; C009170:rhazinilam