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.

中文翻译：

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氧化氨基催化和金催化对映选择性合成 α-季异色满

一种结合氧化氨基催化和金催化的新策略可以制备手性 α-季异色满，这是天然产物和合成生物活性化合物中普遍存在的基序。第一步，通过 DDQ 和氨基酸衍生的伯胺催化剂的氧化还原，将 α-支化醛和炔丙醇转化为具有优异光学纯度 (>90% ee) 的 α-季醚。随后的金 (I) 催化的分子内氢化芳基化得到保留了四元立构中心的异色满产物。第二种方法探索使用烯丙醇作为氧化偶联的反应伙伴，以提供通常具有较低对映体纯度的α-季醚。异色满产物的立体保留环化是通过以乙酸烯丙酯作为反应手柄的分子内傅克型烷基化来实现的。对这些 α-四元异色烷的大量合成阐述和生物学研究突出了该方法的潜在适用性。