Selective synthesis of imidazolidine-2-thiones via ring expansion of aziridine-2-carboxylates with isothiocyanates

Recent applications of aziridine ring expansion reactions in heterocyclic synthesis

“…88 A similar reaction of trans-aziridine-2-carboxylates 169 with isothiocyanates leads to the formation of trans-imidazolidine-2-thiones 170 in regioselective and stereoselective manners (Scheme 51). 89 The steric and electronic effects in substrates play a role resulting into epimerization of starting aziridines in some cases and/or formation of imidazolidin-4-ones. The formation of trans-imidazolidine-2-thiones is suggested via a zwitterionic key intermediate 171, generated by a nucleophilic attack of lone pair on aziridine nitrogen onto the electrophilic carbon of isothiocyanates.…”

Zinc Tetrafluoroborate-Mediated Ring Expansion of trans-Aziridine-2-carboxylates to cis-2-Iminothiazolidines and cis-Thiazolidine-2-iminium Tetrafluoroborates and Evaluation of Antimicrobial Activity

“…In a previous publication, we described the ring expansion of trans -aziridine-2-carboxylates into trans -imidazolidine-2-thiones as the major products in the absence of a catalyst, via a complete regio- and stereoselective process (Scheme a) . Herein, we show that in the presence of a Lewis acid, the behavior of aziridine-2-carboxylates and isothiocyanates is different.…”

“…In a previous publication, we described the ring expansion of trans -aziridine-2-carboxylates into trans -imidazolidine-2-thiones as the major products in the absence of a catalyst, via a complete regio- and stereoselective process ( Scheme 1 a). 19 Herein, we show that in the presence of a Lewis acid, the behavior of aziridine-2-carboxylates and isothiocyanates is different. In fact, utilizing zinc tetrafluoroborate as a mediator in these reactions leads exclusively to cis -2-iminothiazolidines or cis -thiazolidine-2-iminium tetrafluoroborates ( Scheme 1 b).…”

“…The strong Lewis acid property of Zn(BF 4 ) 2 • xH 2 O, which led to the formation of a complex with the resulting iminothiazolidine, may explain the amount (1 equiv) of Lewis acid used in this reaction. Purification on a It is worth noting that we have already shown in a previous work 19 that when the reaction is conducted in the absence of a Lewis acid, the aziridine nitrogen atom, uncoordinated in this case, attacks the electrophilic carbon of the isothiocyanate to give a zwitterion as the key intermediate. This undergoes regiospecific C−N bond cleavage to give a linear zwitterionic intermediate, which cyclizes to imidazolidine-2-thione involving the attack of the highly nucleophilic nitrogen anion onto the benzylic position.…”