Structure Guided Design of VANOL-Imidodiphosphorimidate Catalysts for the Catalytic Enantioselective Bromospiroketalization Reaction

Abstract

This report presents a structure-guided approach for the optimization of VANOL-derived imidodiphosphorimidates as catalysts for the halonium-ion-induced spiroketalization reaction. Fine tuning of the catalyst active site, alongside enhanced acidity, was required to achieve high catalytic activity for the spiroketalization reaction. A wide range of substrates was well tolerated yielding halogenated spiroketals in high yields, diastereoselectivities, and enantioselectivities.

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

“…As such we examined the catalyst’s aptitude to enforce high levels of enantiofacial discrimination for a continuous series of selective reactions. Because a single chiral catalyst must enable stereocontrol over discrete reaction events this approach to chiral molecule construction is much less common and to our knowledge, only two examples have been reported with IDPis. , These factors make sequential reactions an appealing assessment of the catalyst’s ability to facilitate a difficult chemical transformation, although the reaction type is a secondary aspect of the study. In this context, we identified a Prins-semipinacol rearrangement as a stringent test that involves structurally distinct reactive intermediates and bond forming steps to produce stereochemically dense spirocycles.…”

“…The structure of chiral organocatalysts continues to evolve with each notable design gaining enhanced function over enantioselective bond construction. , Asymmetric Brønsted acid catalysis exemplifies this where iterative changes to the catalyst structure has enabled marked increases in selectivity and reactivity for a diverse set of organic transformations. − Indeed these efforts have led to generations of rational catalyst designs that have developed from simple modifications of the catalyst substituents to the introduction of strongly acidic dimeric catalyst structures (Figure ). , Despite this significant progression in structure, new Brønsted acid catalysts typically retain the key molecular features that have led to a good performance with older designs. For example, N-triflyl phosphoramide catalysts were introduced to overcome the reactivity barriers associated with weakly basic carbonyl substrates but contain the same sterically bulky groups associated with the high selectivity imparted by BINOL-derived phosphoric acids .…”