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Abstract

The developments of Brønsted acid catalyzed asymmetric syntheses of acetals and a novel class of confined Brønsted acid catalysts are described. The first highly enantioselective intramolecular transacetalization reaction catalyzed by the chiral BINOL‐derived phosphoric acid TRIP was developed to access chiral acetals with the acetal carbon as the only stereogenic center.
The practical utility of the catalytic asymmetric transacetalization reaction was demonstrated in a kinetic resolution of homoaldol acetals. Both secondary and tertiary homoaldols were resolved with high enantioselectivity using phosphoric acid STRIP based on a 1,1′‐spirobiindane backbone.
The first catalytic asymmetric spiroacetalization reaction was developed, enabling access to small unfunctionalized spiroacetal compounds, including the natural product olean, which possesses a spiroacetal center as the only source of chirality. In addition, the catalyst controlled access to thermodynamic and nonthermodynamic spiroacetals was achieved offering a solution to this long standing issue in synthesis of spiroacetal natural products.
Most significantly, to enable the spiroacetalization reaction a novel class of chiral Brønsted acids, termed confined Brønsted acids was designed and developed. Confined Brønsted acids based on a C₂‐symmetric imidodiphosphate anion feature an extremely sterically demanding chiral microenvironment with a single catalytically relevant and geometrically constrained bifunctional active site. This catalyst design is expected to find wide utility in various asymmetric reactions involving small and functionally unbiased substrates.