A Concise Access to 6-Azabicyclo[3.1.0]hexanes via High-Pressure Promoted Cycloaddition Reaction of Azides to ABH

Cycloaddition reaction of electron-deficient azides (5a, b) to 2-azabicyclo[2.2.1]hept-5-en-3-one (ABH) (1) was accelerated by high-pressure, leading to a mixture of regioisomeric triazolines (6) in good yields.Then, 6 were in turn, through photolysis and ring opening sequences, converted to 6-azabicyclo[3.1.0]hexanes(8).Prompted by the recent reports of the intriguing biological activities of methano-nucleosides, 1 we have previously reported the preparation of methano-cabocyclic nucleoside (4; X=CH 2 ) whose cyclopentane ring is conformationally restricted due to the methylene group fused between the 2' and 3' positions (Scheme 1). 2 In due course, we have also interested in azamethano-carbocyclic nucleosides (4; X=N-R), and we disclose in this paper a concise construction of 6-azabicyclo[3.1.0]hexane(3; X=N-R) that may serve as a versatile intermediate for further transformation to azamethano-carbocyclic nucleosides (4; X=N-R), where a key method utilizes an intermolecular [2+3] cycloaddition reaction of azides to Nsubstituted 2-azabicyclo[2.2.1]hept-5-en-3-ones (ABH) (1) at high-pressure.In general, cycloaddition reactions of acyl azides to olefins take place through 1,3-dipolar reaction path to give triazolines as primary products, and the subsequent decomposition of the resulted triazolines affords N Y O N Y O X