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oai:figshare.com:article/34020607 2026-09-29T03:07:14Z category_4 category_8 category_13 category_21 category_873 category_734 category_931 category_61 category_132 category_133 portal_63 item_type_6 month_year_09_2026

Mechanistically Agnostic Aliphatic N–H Transmutations Enabled by Interrupted Nitrogen Deletion Isabelle E. Petrucci (25133893) Jeanne Masson-Makdissi (3188688) Zisheng Xue (25133896) Caroline McCleary (16833059) Michal P. Glogowski (10112380) Mark D. Levin (2233804) Biochemistry Microbiology Genetics Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Information Systems not elsewhere classified Developmental Biology Infectious Diseases Plant Biology systematically examined across key isodiazene intermediate interrupted nitrogen deletion form dearomatized vinylcyclopropanes productive vinylcyclopropane formation mediated ring closure fused piperidines via 2 </ sub requisite vinylcyclopropane polar ring piperidines react corresponding piperidines valuable class unique reactivity undergo rh synthetic tools skeletal atoms dearomatization penalty corresponding thiane corresponding dihydropyran corresponding cyclohexanone comparatively underexplored carbon monoxide aromatic systems anomeric amide allow access aliphatic replacements Reactions which promote the replacement of skeletal atoms are emerging as a valuable class of synthetic tools. Despite significant recent progress on transmutations of aromatic systems, aliphatic replacements are comparatively underexplored. Herein, we demonstrate three aliphatic transmutations on heteroaryl-fused piperidines via an interrupted nitrogen deletion. These piperidines react with an anomeric amide to form dearomatized vinylcyclopropanes that can undergo Rh-catalyzed [5 + 1] cycloadditions with carbon monoxide to afford the corresponding cyclohexanone, polar ring-opening in the presence of I₂ and H₂O followed by base-mediated ring closure to give the corresponding dihydropyran, or photochemically promoted radical cyclization with a sulfonothioate to provide the corresponding thiane. The propensity for the key isodiazene intermediate to partition to the requisite vinylcyclopropane or its isomeric cyclopentene deletion product was systematically examined across a range of heterocycles. The dearomatization penalty of each heterocycle, measured computationally via isodesmic calculations, was found to predict the likelihood of productive vinylcyclopropane formation. This work demonstrates three novel aliphatic transmutations: NH-to-CO, NH-to-O, and NH-to-S, leveraging the unique reactivity of an interrupted nitrogen deletion to allow access to ketones, dihydropyrans, and thianes from the corresponding piperidines. 2026-09-28T00:00:00Z Text Journal contribution 10.1021/jacs.6c13570.s001 https://figshare.com/articles/journal_contribution/Mechanistically_Agnostic_Aliphatic_N_H_Transmutations_Enabled_by_Interrupted_Nitrogen_Deletion/34020607 CC BY-NC 4.0