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.
摘要：
结合氧化氨基催化和金催化的新策略允许制备手性α-季异色满，在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,α-支化醛和炔丙基醇通过用DDQ和氨基酸衍生的伯胺催化剂氧化改性转化为具有优异光学纯度(>90%ee)的α-季醚。随后的金（I）催化的分子内氢芳基化提供了保留有四元立体中心的异色满产物。第二种方法探索了使用烯丙基醇作为氧化偶联的反应伙伴，以提供对映体通常较低的α-季醚。通过以烯丙基乙酸酯作为反应柄的分子内Friedel-Crafts型烷基化，可以实现对异色满产物的立体抑制环化。对这些α-季代异色满的许多合成阐述和生物学研究突出了所提出方法的潜在适用性。
