Gao Mingchun, Ruiz Jose M, Jimenez Emily, Lo Anna, Laconsay Croix J, Fettinger James C, Tantillo Dean J, Shaw Jared T
Department of Chemistry, University of California One Shields Avenue Davis California 95616 USA
Chem Sci. 2023 May 11;14(23):6443-6448. doi: 10.1039/d3sc00734k. eCollection 2023 Jun 14.
Substrates engineered to undergo a 1,4-C-H insertion to yield benzocyclobutenes resulted in a novel elimination reaction to yield -quinone dimethide (-QDM) intermediates that undergo Diels-Alder or hetero-Diels-Alder cycloadditions. The analogous benzylic acetals or ethers avoid the C-H insertion pathway completely and, after hydride transfer, undergo a de-aromatizing elimination reaction to -QDM at ambient temperature. The resulting dienes undergo a variety of cycloaddition reactions with high diastereo- and regio-selectivity. This is one of the few examples of catalytic generation of -QDM without the intermediacy of a benzocyclobutene and represents one of the mildest, ambient temperature processes to access these useful intermediates. This proposed mechanism is supported by DFT calculations. Moreover, the methodology was applied to the synthesis of (±)-isolariciresinol in 41% overall yield.
经过工程设计以进行1,4-C-H插入反应生成苯并环丁烯的底物，会引发一种新型消除反应，生成可进行狄尔斯-阿尔德（Diels-Alder）或杂狄尔斯-阿尔德（hetero-Diels-Alder）环加成反应的对醌二甲烷（-QDM）中间体。类似的苄基缩醛或醚则完全避开C-H插入途径，在氢化物转移后，于室温下发生去芳构化消除反应生成对醌二甲烷。生成的二烯会以高非对映选择性和区域选择性进行各种环加成反应。这是少数几个无需苯并环丁烯中间体催化生成对醌二甲烷的例子之一，也是获取这些有用中间体最温和的室温方法之一。该提出的机理得到了密度泛函理论（DFT）计算的支持。此外，该方法被应用于以41%的总收率合成（±）-异落叶松脂醇。
