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4825613 
Journal Article 
A new synthesis of 2-azabicyclo[2.1.1]hexanes 
Lescop, C; Mévellec, L; Huet, F 
2001 
Yes 
Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904 
66 
12 
4187-4193 
English 
11397152 
WOS:000169235700012 
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.