An efficient synthesis of the 2-azabicyclo[2.1.1]hexane ring system has been accomplished starting from cis-cyclobut-3-ene-1,2-dicarboxylic anhydride 7, which was prepared using a photochemical method. The key step of this new strategy involved a stereoselective electrophilic addition of phenylselenyl bromide to the double bond of cyclobutene dicarbamate 16 derived from 7. The subsequent ring closure of 17a in the presence of sodium hydride afforded the 2-azabicyclohexane compound 18 with a satisfying overall yield. Reductive removal of the phenylselenyl group and subsequent deprotection led rapidly to the amino derivative 4a functionalized on the carbon ring. Syntheses of the hydroxy and carboxylic derivatives 4b,c were then achieved from the intermediary disulfonamide 23. Displacement of the activated amino group by potassium acetate yielded hydroxy derivative 4b after three additional steps. Finally, oxidation of the alcohol function of 4b under Jones conditions followed by hydrogenolysis afforded the carboxylic derivative 4c, which is the first reported beta-isomer of 2,4-methanoproline 1.

中文翻译：

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2-氮杂双环[2.1.1]己烷的新合成。

从顺式-环丁-3-烯-1,2-二羧酸酐7开始，已经完成了2-氮杂双环[2.1.1]己烷环系统的有效合成，该顺式-环丁-3-烯-1,2-二羧酸酐是使用光化学方法制备的。该新策略的关键步骤涉及将苯硒基溴化物立体选择性地亲电子加成至衍生自7的环丁二氨基甲酸酯16的双键。随后在氢化钠存在下17a的闭环反应使2-氮杂双环己烷化合物18具有令人满意的总体让。还原性除去苯基硒烯基并随后脱保护，迅速导致在碳环上官能化的氨基衍生物4a。然后从中间体二磺酰胺23合成羟基和羧酸衍生物4b，c。在另外三个步骤之后，用乙酸钾置换活化的氨基，得到羟基衍生物4b。最后，在琼斯条件下氧化4b的醇官能团，然后进行氢解，得到羧酸衍生物4c，它是2,4-methanoproline 1的第一个报道的β-异构体。