A Bulky Imidodiphosphorimidate Brønsted Acid Enables Highly Enantioselective Prins-semipinacol Rearrangements

Abstract

The development of BINOL-derived Brønsted acid catalysts has been profoundly guided by rational design, with carefully implemented structural changes leading to unique generations of catalysts with enhanced reaction capabilities. This approach to catalyst optimization has promoted the integration of knowledge gathered in optimizing prior eras of Brønsted acids and ultimately, the molecular features that have contributed to the success of previous designs are preserved. Of these, the large substituents at the 3 and 3’ positions of the BINOL backbone are the most critical with almost every newly developed structure possessing this feature. However, imidodiphosphorimidate (IDPi) catalysts are not synthetically well-suited to contain the same sterically bulky groups associated with the high selectivity imparted by previously implemented catalyst structures. Herein, we have leveraged the moderate size (as compared to TRIP and 9-anthryl) but high applicability of the 9-phenanthryl substituent to synthesize a sterically demanding IDPi. Using computed descriptors, we survey the catalyst properties of known structures to demonstrate this catalyst to be both unique and one of the bulkiest IDPi yet synthesized. The applicability of the catalyst was evaluated in the construction of stereochemically dense spirocycles generated via an asymmetric Prins-semipinacol reaction sequence. Transition state calculations were deployed to interrogate the origins of the superior enantioselectivity and these demonstrate the mechanistic hallmarks of the 9-phenanthryl substituent can be generalized to a genuinely different class of Brønsted acid catalyst. Ultimately, providing the basis for the development of general catalyst design principles and the translation of “privileged” substituents across unique eras of Brønsted acid catalyst structures.