Stereocontrol via Propeller Chirality in FLP-Catalyzed Asymmetric Hydrogenation.

Utilization of chiral frustrated Lewis pairs as catalysts in enantioselective hydrogenation of unsaturated molecules represents a promising approach in asymmetric synthesis. In our effort to improve our current understanding of the factors governing the stereoselectivity in these catalytic processes, herein we examined the mechanism of direct hydrogenation of aromatic enamines catalyzed by a binaphthyl-based chiral amino-borane. Our computational analysis reveals that only one particular conformer of the key borohydride reaction intermediate can be regarded as a reactive form of this species. This borohydride conformer has a well-defined chiral propeller shape, which induces facial selectivity in the hydride transfer to pro-chiral iminium intermediates. The propeller chirality of the reactive borohydride conformer is generated by the axially chiral binaphthyl scaffold of the amino-borane catalyst through stabilizing π-π stacking interactions. This new computational insight can be readily used to interpret the high degree of stereoinduction observed for these reactions. We expect that the concept of chirality relay could be further exploited in catalyst design endeavors.

Replacing C6F5 groups with Cl and H atoms in frustrated Lewis pairs: H2 additions and catalytic hydrogenations.

2-(Dialkylamino)phenylboranes containing the BXZ group, where X, Z = C6F5, Cl, and H, were prepared in a few synthetic steps and demonstrated the cleavage of H2 under mild conditions. Depending on the nature of the dialkylamino group, X, and Z, the stability of the produced zwitterionic H2 adducts varies from isolated solids indefinitely stable in an inert atmosphere to those quickly equilibrating with the initial aminoborane and H2. Using a combined experimental/computational approach on a series of isostructural aminoboranes (dialkylamino = 2,2,6,6-tetramethylpiperid-1-yl), it was demonstrated that the electronegativity and the steric effect of the substituents generally follow the trend C6F5 ∼ Cl ≫ H. This observation is useful for designing new FLPs for practical applications. As an example, we demonstrated the hydrogenation of alkynes to cis-alkenes under mild conditions that was catalyzed by a chloro-analogue of the C6F5-substituted aminoborane developed previously. The presence of a BHCl group in the aminochloroboranes or in their H2 adducts features facile redistribution of the H and Cl atoms and the formation of polychloro and polyhydrido species.