Saturated oxygen-containing heterocycles are present in numerous natural products and biologically active compounds. While the oxa-Pictet–Spengler reaction conventionally serves as a traditional synthetic strategy for preparing arene-fused tetrahydropyrans (THPs), existing methods typically involve harsh conditions. Disclosed herein is the development of a mild photocatalytically triggered oxa-Pictet–Spengler reaction of ethers providing a synthetic approach to fused THP compounds. The tuned dual photo/hydrogen-atom transfer (HAT) catalysis enables site- and chemoselective C–H functionalization at the benzylic ether, which results in the formation of a benzoate acetal intermediate. The key intermediate is then exposed to subsequent Lewis acid catalysis, thus facilitating oxocarbenium ion generation and ring closure. Notably, this combination strategy successfully addresses concerns related to the overoxidation inherent in photocatalytic systems.

中文翻译：

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醚类 Oxa-Pictet-Spengler 反应的光催化和路易斯酸联合催化策略

饱和含氧杂环存在于许多天然产物和生物活性化合物中。虽然氧杂-皮克泰-斯宾格勒反应通常是制备芳烃稠合四氢吡喃（THP）的传统合成策略，但现有方法通常涉及苛刻的条件。本文公开了温和光催化引发的醚 oxa-Pictet-Spengler 反应的开发，提供了稠合 THP 化合物的合成方法。调谐的双光/氢原子转移 (HAT) 催化能够在苄基醚上进行位点和化学选择性 C-H 官能化，从而形成苯甲酸酯缩醛中间体。然后将关键中间体暴露于随后的路易斯酸催化，从而促进氧碳鎓离子的生成和闭环。值得注意的是，这种组合策略成功解决了与光催化系统固有的过度氧化相关的问题。