Asymmetric Synthesis of NOSPIN Derivatives

The spirobiindane scaffold represents one of the most important privileged structures for developing chiral catalysts and ligands. However, 7-amino-7'-hydroxyl-1,1'-spirobiindane (NOSPIN)-a key spirobiindane precursor for diverse chiral catalysts and ligands-lacks efficient synthetic methods, and its asymmetric synthesis remains an unmet challenge. In this work, we develop a concise and efficient method for the asymmetric synthesis of 3,3'-Diaryl-NOSPINs. The success of this strategy relies on two key steps: a highly enantioselective and diastereoselective rhodium-catalyzed double conjugate arylation, and a diastereoselective and chemoselective Friedel-Crafts-type reaction of free aniline. Furthermore, we demonstrated the utility of the newly synthesized scaffold in divergent catalyst/ligand synthesis and showcased the superior performance of the corresponding ligand in asymmetric catalysis. This work represents the first asymmetric synthesis of NOSPINs and provides a practical approach to this privileged structure, paving the way for its broader application.