2-氮杂金刚烷-6-酮的合成：一种缺失的异构体

Wu Jianbo, Leas Derek A, Dong Yuxiang, Wang Xiaofang, Ezell Edward L, Stack Douglas E, Vennerstrom Jonathan L

College of Pharmacy and Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.

Department of Chemistry, University of Nebraska at Omaha, Omaha, Nebraska 68182, United States.

ACS Omega. 2018 Sep 30;3(9):11362-11367. doi: 10.1021/acsomega.8b01819. Epub 2018 Sep 18.

2-Azaadamantan-6-one and its Boc and ethylene ketal derivatives were synthesized from 9-oxo -bicyclo[3.3.1]non-6-ene-3-carboxylic acid. Similarly, the Cbz, Boc, and ethylene ketal derivatives of 2-azaadamantan-4-one were synthesized from -bicyclo[3.3.1]non-6-ene-3-carboxylic acid. Key steps were Curtius rearrangements to form benzyl carbamates, followed by spontaneous intramolecular attack of the carbamate nitrogen on transient bromonium ion or epoxide intermediates to effect ring closure to azaadamantane intermediates. The reaction sequence leading to 2-azaadamantan-6-one is consistent with the formation of a transient tetracyclic keto aziridine intermediate.

2-氮杂金刚烷-6-酮及其Boc和乙烯缩酮衍生物由9-氧代-双环[3.3.1]壬-6-烯-3-羧酸合成。类似地，2-氮杂金刚烷-4-酮的Cbz、Boc和乙烯缩酮衍生物由双环[3.3.1]壬-6-烯-3-羧酸合成。关键步骤是进行库尔提斯重排以形成苄基氨基甲酸酯，随后氨基甲酸酯氮对瞬态溴鎓离子或环氧化物中间体进行自发的分子内进攻，从而实现环化生成氮杂金刚烷中间体。导致2-氮杂金刚烷-6-酮的反应序列与瞬态四环酮氮丙啶中间体的形成一致。