Asymmetric Synthesis of NOSPIN Derivatives

ABSTRACT 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.