Synthesis of a Conformationally Stable Atropisomeric Pair of Biphenyl Scaffold Containing Additional Stereogenic Centers

The synthesis of a new CF(3)-containing stereogenic atropisomeric pair of ortho-disubstituted biphenyl scaffold is presented. The atropisomers are surprisingly conformationally stable for isolation. X-ray structures show that their stability comes from an intramolecular hydrogen bond formation from their two hydroxyl groups and renders the spatial arrangement of their peripheral CF(3) and CH(3) groups very different. The synthesized stereogenic scaffold proved to be effective in catalyzing the asymmetric N-nitroso aldol reaction of enamine and nitrosobenzene. Compared to similar scaffolds without CF(3) groups, one of our atropisomer exhibits an increase in enantioselectivity in this reaction.