Synthesis Of Chiral Biphenyl Backbones And Their Applications In Asymmetric Catalysis

Racemic backbones 2-amino-2'-hydroxy-6,6'-dimethyl-l,l'-biphenyl la and 2-amino-2'-hydroxy-4,4',6,6'-tetramethyl-l,1'-biphenyl 1b were synthesized from o-methylaniline and 2,4-dimethylaniline via nitration, diazotation/iodination, Ullmann coupling, selective reduction, diazotation/hydrolysis and hydrogenation. The overall yields of six steps were 23% and 25%, respectively.Two diasteromeric salts were formed from racemic compound 1 and S-(+)-10-camphorsulfonic acid, resolution was accomplished by the different reaction rate of the two salts with saturated aqueous NaHCO3. Up to 99.5% ee of (+)-1 and (-)-l in 48-52% of yields were obtained. This resolution can be carried out by strong basic hydrolysis of diasteromeric amide, which was derived from racemic backbone and S'-(+)-10-camphorsulfonyl chloride and separated via column chromatography. The absolute configuration of (-)-la was assigned by X-ray analysis.Eleven chiral Schiff-base N,O ligands (9a~9j, 10) were synthesized from R-(+)-1a, R-(+)-lb and R-(+)-2-amino-2'-hydroxy-l,l'-binaphthyl. These ligands were applied in asymmetric hetero-ene reaction of 4-nitrobenzaldehyde and2-methoxypropene, up to 79% ee was obtained.Two new P,N ligands R-(-)-18a and R-(-)-18b were synthesized from R-(+)-1a and R-(+)-lb in six steps, respectively. Under optimized conditions, their Cu(I) complexes were successfully applied in the asymmetric 1,4-conjugate additions of diethylzinc to acyclic enones. Up to 96.1% ee was obtained.