Abstract

Convergent total synthesis of (±)-apomorphine hydrochloride was accomplished by an approach that employs in the key step a sequence of transformations involving a [4+2]-cycloaddition reaction followed by a hydrogen migration. Through this sequence of transformations, the desired aporphine core was obtained regioselectively in 75% isolated yield. Since only one regioisomer was produced in the key step of the synthesis, a polar [4+2]-cycloaddition mechanism was proposed. Furthermore, NMR experiments and theoretical calculations were carried out to elucidate the hydrogen migration mechanism. (±)-Apomorphine hydrochloride was achieved after 9 steps in an overall yield of 8% involving benzyne chemistry.

Convergent total synthesis of (±)-apomorphine hydrochloride was accomplished by an approach that employs in the key step a sequence of transformations involving a [4+2]-cycloaddition reaction followed by a hydrogen migration. Through this sequence of transformations, the desired aporphine core was obtained regioselectively in 75% isolated yield. Since only one regioisomer was produced in the key step of the synthesis, a polar [4+2]-cycloaddition mechanism was proposed. Furthermore, NMR experiments and theoretical calculations were carried out to elucidate the hydrogen migration mechanism. (±)-Apomorphine hydrochloride was achieved after 9 steps in an overall yield of 8% involving benzyne chemistry.

中文翻译：

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通过苯炔化学聚合全合成（±）-阿扑吗啡：洞悉关键步骤涉及的机理

摘要

（±）-阿扑吗啡盐酸盐的总聚合合成是通过一种方法完成的，该方法在关键步骤中采用了一系列转化过程，其中涉及[4 + 2]-环加成反应，然后进行氢迁移。通过该转化序列，以75％的分离产率区域选择性地获得了所需的甲啡肽核心。由于在合成的关键步骤中仅产生一种区域异构体，因此提出了极性的[4 + 2]-环加成机理。此外，进行了NMR实验和理论计算以阐明氢的迁移机理。经过9个步骤，获得了（±）-Apomorphine盐酸盐，涉及苯炔化学的总收率为8％。

（±）-阿扑吗啡盐酸盐的总聚合合成是通过一种方法完成的，该方法在关键步骤中采用了一系列转化过程，其中涉及[4 + 2]-环加成反应，然后进行氢迁移。通过该转化序列，以75％的分离产率区域选择性地获得了所需的甲啡肽核心。由于在合成的关键步骤中仅产生一种区域异构体，因此提出了极性的[4 + 2]-环加成机理。此外，进行了NMR实验和理论计算以阐明氢的迁移机理。经过9个步骤，获得了（±）-Apomorphine盐酸盐，涉及苯炔化学的总收率为8％。