Theoretical investigation of the regioselective ring opening of 2-methylaziridine. Lewis acid effect

Vicinal difunctionalization of carbon–carbon double bond for the platform synthesis of trifluoroalkyl amines

“…In general, ring opening of substituted aziridinium ions by nucleophiles leads to mixture of constitutional isomers, which is governed by the nature of substituents of the heterocycle 70 . Among these substituents, the trifluoromethyl group attached to the aziridine carbon lowers the activation energy of the ring opening considerably at both C-2 and C-3 position, but in general ring opening is favored at the C-3 position both thermodynamically and kinetically 71 . Taking the advantage of the electronic influence on the ring opening could enable the selective heterodifunctionalizations of the trifluoromethyl alkenes via aziridinium intermediates.…”

Synthetic Applications of Aziridinium Ions

“…Aziridines are bifurcated into "activated" ones bearing electron-withdrawing substituents at the ring nitrogen and "nonactivated" ones with electron-donating substituents [14] (Figure 1). Activated aziridines are quite reactive toward most nucleophiles, while nonactivated aziridines are inert unless they are activated as aziridinium ions or their equivalents by proper electrophiles including alkyl, acyl, trimethylsilyl, and Lewis acids [15,16]. When the simple aziridine without any substituent on the ring is protonated as an aziridinium ion, the ring strain is increased by 47 kJ/mol [17].…”

“…Most ring-opening reactions of nonactivated aziridines proceed with breakage of the bond between C and N, such as A or B, with the assistance of electrophiles after the formation of aziridinium ions. Experimental and theoretical studies have shown that nonactivated aziridine is possibly not serving as Activated aziridines are quite reactive toward most nucleophiles, while nonactivated aziridines are inert unless they are activated as aziridinium ions or their equivalents by proper electrophiles including alkyl, acyl, trimethylsilyl, and Lewis acids [15,16]. When the simple aziridine without any substituent on the ring is protonated as an aziridinium ion, the ring strain is increased by 47 kJ/mol [17].…”

“…Most ring-opening reactions of nonactivated aziridines proceed with breakage of the bond between C and N, such as A or B, with the assistance of electrophiles after the formation of aziridinium ions. Experimental and theoretical studies have shown that nonactivated aziridine is possibly not serving as a 1,3-dipole, as shown in C and D, while activated aziridines can be utilized for a cyclization Thus, most reactions with nonactivated aziridines are carried out with the formation of aziridinium ion as a quaternary ammonium at first, which is created via the chemical bond between nucleophilic and basic ring nitrogen and an applied electrophile [15,16]. The aziridinium ion as an ionic intermediate is a well-known chemical species called "nitrogen mustard", including the notorious chemical warfare agent VX [O-ethyl S- [2-(diisopropylamino) ethyl] methylphosphonothioate [20].…”

“…Lastly, aziridinium ylides schematized below (Eq 3i and 3ii, in Scheme 2) can be created by addition of a ring-nitrogen to alkyne (Eq 3i, in Scheme 2) or diazo compound (Eq 3ii, in Scheme 2). Thus, most reactions with nonactivated aziridines are carried out with the formation of aziridinium ion as a quaternary ammonium at first, which is created via the chemical bond between nucleophilic and basic ring nitrogen and an applied electrophile [15,16]. The aziridinium ion as an ionic intermediate is a well-known chemical species called "nitrogen mustard", including the notorious chemical warfare agent VX [20].…”