Brønsted Acid-Catalyzed, Diastereo- and Enantioselective, Intramolecular Oxa-Diels–Alder Reaction of ortho-Quinone Methides and Unactivated Dienophiles

A stereoselective, phosphoric acid-catalyzed synthesis of dihydrochromenochromenes has been developed using transient ortho-quinone methides (o-QMs). Three contiguous stereogenic centers were formed with excellent yields, partially as single diastereomers and with moderate to excellent enantioselectivity. This intramolecular hetero-Diels–Alder reaction features unactivated dienophiles and o-QM precursors tethered by a simple phenoxy linker and furnishes cycloadducts with a prominent structural motif found in many natural products. Through an appropriate choice of dienophile configuration and backbone substitution either exo- or endo-stereoisomers were formed selectively with up to a 96:04 enantiomeric ratio.

本研究开发了一种以瞬态邻亚甲基苯醌（transient ortho-quinone methides, o-QMs）为反应底物的磷酸催化二氢苯并吡喃并苯并吡喃立体选择性合成方法。该反应可构建三个连续的手性中心，产物产率优异，部分产物仅以单一非对映异构体形式生成，且对映选择性处于中等至优异水平。此分子内杂狄尔斯-阿尔德（intramolecular hetero-Diels–Alder）反应以简单苯氧基连接臂连接的未活化亲双烯体与邻亚甲基苯醌前体为底物，所得环加成产物带有诸多天然产物中普遍存在的典型结构基元。通过合理选择亲双烯体的构型与骨架取代模式，可选择性生成外式或内式立体异构体，最高对映体比率可达96:4。