{Reference Type}: Journal Article
{Title}: Enantioselective Synthesis of α-Quaternary Isochromanes by Oxidative Aminocatalysis and Gold Catalysis.
{Author}: Waser P;Faghtmann J;Gil-Ordóñez M;Kristensen A;Svenningsen EB;Poulsen TB;Jørgensen KA;
{Journal}: Chemistry
{Volume}: 30
{Issue}: 38
{Year}: 2024 Jul 5
{Factor}: 5.02
{DOI}: 10.1002/chem.202401354
{Abstract}: A novel strategy that combines oxidative aminocatalysis and gold catalysis allows the preparation of chiral α-quaternary isochromanes, a motif that is prevalent in natural products and synthetic bioactive compounds. In the first step, α-branched aldehydes and propargylic alcohols are transformed into α-quaternary ethers with excellent optical purities (>90 % ee) via oxidative umpolung with DDQ and an amino acid-derived primary amine catalyst. Subsequent gold(I)-catalyzed intramolecular hydroarylation affords the isochromane products with retention of the quaternary stereocenter. A second approach explores the use of allylic alcohols as reaction partners for the oxidative coupling to furnish α-quaternary ethers with generally lower enantiopurities. Stereoretentive cyclization to isochromane products is achieved via intramolecular Friedel-Crafts type alkylation with allylic acetates as a reactive handle. A number of synthetic elaborations and a biological study on these α-quaternary isochromanes highlight the potential applicability of the presented method.