Brønsted Acid Catalyzed Asymmetric S_N2-Type O-Alkylations

Bridging the gap: Brønsted acids catalyze an intramolecular SN2-type alkylation of alcohols with ethers by bridging a pentacoordinate transition state, thus simultaneously activating both the leaving group and nucleophile (see scheme). Density functional calculations provide detailed insight into the course of the reaction and the transition-state structure

Asymmetric spiroacetalization catalysed by confined Brønsted acids

Acetals are molecular substructures that contain two oxygen–carbon single bonds at the same carbon atom, and are used in cells to construct carbohydrates and numerous other molecules. A distinctive subgroup are spiroacetals, acetals joining two rings, which occur in a broad range of biologically active compounds, including small insect pheromones and more complex macrocycles. Despite numerous methods for the catalytic asymmetric formation of other commonly occurring stereocentres, there are few approaches that exclusively target the chiral acetal centre and none for spiroacetals. Here we report the design and synthesis of confined Brønsted acids based on a C2-symmetric imidodiphosphoric acid motif, enabling a catalytic enantioselective spiroacetalization reaction. These rationally constructed Brønsted acids possess an extremely sterically demanding chiral microenvironment, with a single catalytically relevant and geometrically constrained bifunctional active site. Our catalyst design is expected to be of broad utility in catalytic asymmetric reactions involving small and structurally or functionally unbiased substrates

N-Phosphinyl Phosphoramide — A Chiral Brønsted Acid Motif for the Direct Asymmetric N,O-Acetalization of Aldehydes

Fine‐tuning the sites: The readily accessible N‐phosphinyl phosphoramide 1 proved to be highly efficient and enantioselective in catalyzing the title reaction. The synthetic utility of this methodology was demonstrated with the first catalytic asymmetric synthesis of the analgesic pharmaceutical (R)‐chlorothenoxazine (see scheme)

The Catalytic Asymmetric Acetalization

In straitened circumstances: In an asymmetric version of the acid‐catalyzed acetalization of aldehydes, a novel member of the chiral confined Brønsted acid family significantly outperformed previously established catalysts, providing cyclic acetals with excellent enantioselectivity (see scheme; Ar=2‐iPr‐5‐MeC6H3)

Activation of H₂O₂ by Chiral Confined Brønsted Acids: A Highly Enantioselective Catalytic Sulfoxidation

Confined chiral Brønsted acids are shown to catalyze asymmetric oxidations of sulfides to sulfoxides with hydrogen peroxide. The wide generality and high enantioselectivity of the developed method compare even to the best metal-based systems and suggest utility in other asymmetric oxidations

The Catalytic Asymmetric α-Benzylation of Aldehydes

The first aminocatalyzed α-alkylation of α-branched aldehydes with benzyl bromides as alkylating agents has been developed. Using a sterically demanding proline derived catalyst, racemic α-branched aldehydes are reacted with alkylating agents in a DYKAT process to give the corresponding α-alkylated aldehydes with quaternary stereogenic centers in good yields and high enantioselectivities