Direct Aziridination of Nitroalkenes Affording N‑Alkyl‑C‑nitroaziridines and the Subsequent Lewis Acid Mediated Isomerization to β‑Nitroenamines Feiyue Hao, † Haruyasu Asahara,* ,†,‡,§ and Nagatoshi Nishiwaki* ,†,‡ † School of Environmental Science and Engineering, and ‡ Research Center for Material Science and Engineering, Kochi University of Technology, Tosayamada, Kami, Kochi 782-8502, Japan * S Supporting Information ABSTRACT: A mild and highly diastereoselective one-pot synthesis of trans-N-alkyl-C-nitroaziridines was achieved by treatment of nitroalkenes with aliphatic amines and N- chlorosuccinimide. Treatment of the obtained aziridines with a Lewis acid resulted in a facile ring opening reaction, accompanied by rearrangement and isomerization into functionalized (Z)-β-nitroenamines. T he aziridines are an important class of nitrogen-containing heterocycles and can be found in a number of biologically active compounds, such as mitomycin, porfiromycin, and azinomycin. 1 Besides, functionalized aziridines also serve as versatile building blocks in organic synthesis. 1,2 The ring opening reaction of aziridines with nucleophiles affords various 1,2-difunctionalized compounds. 1,2 A substantial number of functionalized aziridines can also be transformed into useful products such as HIV protease inhibitor, 3 communesin, 4 ceramide, 5 oseltamivir, 6 and isochroman 7 through rearrange- ment, cycloaddition, and ring expansion reactions. 2 Among the functionalized aziridines, C-nitroaziridines play an important role in chemical transformations because of the strong electron- withdrawing ability of the nitro group. 8 Hence, the develop- ment of efficient methods for the preparation of C-nitro- aziridines has attracted much attention among organic chemists. Among preparative methods for C-nitroaziridines, the direct aziridination of nitroalkenes is the most efficient approach from a practical viewpoint, as it requires only simple experimental manipulations. N-Imidoaziridines are obtained by treatment of N-aminoimides with nitroalkenes in the presence of an oxidant (Scheme 1, eq 1). 9 NsONHCO 2 Et and TsONHCO 2 Et serve as an N1 unit that can undergo direct aziridination of nitroalkenes under basic conditions to afford N-alkoxycarbonylaziridines (Scheme 1, eq 2). 10 Additionally, N-arylaziridines are also available through the reaction of electron-deficient nitroalkenes with aromatic amines followed by ring closure (Scheme 1, eq 3). 11 Unexpectedly, there are no reports on the synthesis of N- alkyl-C-nitroaziridines from nitroalkenes through direct aziridi- nation, except for the multistep synthesis via α-bromoni- troalkenes; however, the substrate scope is not investigated further (Scheme 1, eq 4). 12 Thus, a facile and efficient aziridination of nitroalkenes for the synthesis of N-alkylated nitroaziridines is of great interest. As part of our continuing interest in methods for the direct functionalization of the 2-quinolone framework, we achieved the direct aziridination by sequential treatment of 3-nitro-2- quinolones with an amine and N-chlorosuccinimide (NCS) (Scheme 1, eq 5). 13 Inspired by this protocol, we envisaged that direct aziridination of nitroalkenes might proceed to afford N- alkyl-C-nitroaziridines by sequential treatment with aliphatic amine and NCS (Scheme 1, eq 6). When β-nitrostyrene 1a was reacted with propylamine 2a and NCS at room temperature in THF in the presence of Et 3 N, N-propyl-C-nitroaziridine 3a was successfully obtained (Sup- porting Information (SI), Table S-1, entry 1). In the 1 H NMR, signals for the ring protons H2 and H3 were observed at 3.85 and 4.90 ppm, respectively, with a coupling constant of 1.6 Hz, located in the range (≤2 Hz) for the trans configuration. 14 Moreover, a correlation between protons H3 and Ho of the benzene ring in the NOESY spectrum revealed the resultant aziridine is a trans isomer. We also confirmed that the product was not formed via cis-isomer (SI). Screening of the reaction conditions, such as solvents, bases, temperature, and molar ratio of reagents, increased the yield to 85%; THF was used as the solvent and Cs 2 CO 3 (1.1 equiv) as the base, together with a slightly excess amount of propylamine 2a (1.1 equiv) and NCS (1.1 equiv) at room temperature (SI, Table S-1). The conjugate addition of amine to 1a affords intermediate 5, in which the conformation is fixed by an intramolecular hydrogen bond (Scheme 2). Thus, NCS approaches to 5 from the anti-direction of the aromatic group to avoid the steric hindrance, affording the adduct 6. The subsequent backside attack of the amino group affords aziridine 3a with the trans configuration (Path a). 12,14a Meanwhile, the competitive proton transfer followed by elimination of anionic nitromethane leads to imine 4a (Path b). 15 Indeed, 4a was quantitatively obtained when the reaction was conducted in the absence of NCS. Although the yield of the conversion of β-nitrostyrene 1a into aziridine 3a reached up to 85%, the isolated yield Received: September 1, 2017 Letter pubs.acs.org/OrgLett © XXXX American Chemical Society A DOI: 10.1021/acs.orglett.7b02724 Org. Lett. XXXX, XXX, XXX-XXX