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

The development of BINOL-derived
Brønsted acid catalysts has
been profoundly guided by rational design, with carefully implemented
structural changes leading to 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 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 of the 9-phenanthryl substituent
to synthesize an IDPi with sizable steric demands. 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 high 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, this work provides the basis for the development of general
catalyst design principles and the translation of “privileged”
substituents across prior eras of Brønsted acid catalysts structures.