Inherently Chiral 6,7-Diphenyldibenzo [e,g][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Inherently chiral 6,7-diphenyldibenzo[e,g][1,4]diazocine (DDD) has been synthesized enantioselectively for the first time via chiral phosphoric acid (CPA)-catalyzed cyclocondensation of readily available [1,1'-biphenyl]-2,2'-diamine (1a) and benzil (2a) in 82% yield, with 98% ee under mild reaction conditions. The strategy could also be applied to racemic biaryl diamines through kinetic resolution. The unexpectedly high interconversion energy barriers between the enantiomers (Delta G = 39.5 kcal/mol) and the chemical stability rendered DDD an ideal platform for developing new chiral ligands and catalysts. Unique inherently chiral DDD-based phosphoramidites, phosphoric acid, mono- and diphosphine ligands were prepared from optically pure diphenol derivative DDDOL as a common precursor. Preliminary asymmetric reactions catalyzed by Pd or Rh in the presence of newly developed ligands exhibited comparable or even better enantioselectivities than the corresponding BINOL- or SPINOL-derived ligands. Density functional theory calculation revealed the origin of the enantioselectivity during the process. [GRAPHICS]

Automated summary

In this study, inherently chiral 6,7-diphenyldibenzo[e,g][1,4]diazocine (DDD) was synthesized enantioselectively for the first time using chiral phosphoric acid (CPA) as a catalyst. The reaction yielded 82% of the desired product with a 98% enantiomeric excess. The method could also be applied to racemic biaryl diamines through kinetic resolution. DDD's high energy barriers and chemical stability make it an ideal platform for developing new chiral ligands and catalysts.