Exchange Processes in Shibasaki’s Rare Earth Alkali Metal BINOLate Frameworks and Their Relevance in Multifunctional Asymmetric Catalysis

Shibasaki’s
rare earth alkali metal BINOLate (REMB) catalysts (REMB; RE = Sc,
Y, La – Lu; M = Li, Na, K; B = 1,1-bi-2-naphtholate; RE/M/B
= 1/3/3) are among the most successful enantioselective catalysts
and have been employed in a broad range of mechanistically diverse
reactions. Despite the phenomenal success of these catalysts, several
fundamental questions central to their reactivity remain unresolved.
Combined reactivity and spectroscopic studies were undertaken to probe
the identity of the active catalyst(s) in Lewis-acid (LA) and Lewis-acid/Brønsted-base
(LA/BB) catalyzed reactions. Exchange spectroscopy provided a method
to obtain rates of ligand and alkali metal self-exchange in the RE/Li
frameworks, demonstrating the utility of this technique for probing
solution dynamics of REMB catalysts. Isolation of the first crystallographically
characterized REMB complex with substrate bound enabled stoichiometric
and catalytic reactivity studies, wherein we observed that substrate
deprotonation by the catalyst framework was necessary to achieve selectivity.
Our spectroscopic observations in LA/BB catalysis are inconsistent
with previous mechanistic proposals, which considered only tris­(BINOLate)
species as active catalysts. These findings significantly expand our
understanding of the catalyst structure in these privileged multifunctional
frameworks and identify new directions for development of new catalysts.