Synthesis and Crystal Structure of 5-(R)-Menthyloxy-butyrolacto-[3,4-b]-2(S)-6(R)-1-N-isopropylaziridine

Owing to the unique properties of the smallest three-membered heterocycle, aziridines are highly versatile synthetic precursors, and have been used as synthons for chiral amines, amino acids, amino alcohols and alkaloids.1,2 Also, because some aziridines existing in natural products display potent antitumor and antibiotic activities, 3,4 much interest has been focused on studying synthetic aziridines.Recently, we reported that chiral 3-bromo-2(5H)-furanone easily reacts with some nucleophiles, such as ethyl acetoacetate, to give chiral bicylo[3.3.0]octenederivatives via tandem asymmetric Michael addition/intramolecular nucleophilic substitution.5 To further research for a new, simple, and effective asymmetric synthetic method, we obtained the title compound, 5-(R)-menthyloxybutyrolacto[3,4-b]-2(S)-6(R)-1-N-isopropylaziridine, via tandem asymmetric reaction of chiral 5-menthyloxy-3-bromo-2(5H)furanone with isopropylamine.In this paper, we report on the synthesis and crystal structure of the title compound (Fig. 1).The title compound was obtained by adding isopropylamine (0.354 g, 6 mmol) under a N2 atmosphere to 20 mL of an acetonitrile solution containing K2CO3 (1.21 g, 16 mmol) and TBAB (2 mmol, 0.644 g), then adding chiral synthon 5menthyloxy-3-bromo-2(5H)-furanone (4 mmol, 1.27 g) to the mixture, and stirring at room temperature until chiral synthon disappeared.The crude product was purified to give the title compound (0.603 g), 51 % yield, m.p. 105 -106˚C.Crystals were grown by slow evaporation from a petroleum-EtOAc solution of the title compound after about one week.