Lewis acid mediated nucleophilic ring opening followed by cycloaddition of 2-aryl-N-tosylaziridines with carbonyl compounds: further support towards an SN2-type mechanism

A highly regioselective SN2-type ring opening of 2-aryl-N-tosylaziridines with carbonyl compounds in the presence of a Lewis acid to afford various 1,3-oxazolidines and 1,2-amino alcohols in excellent yields and moderate to high enantioselectivity is described. The formation of non-racemic products provides convincing evidence for the SN2-type ring opening mechanism. 2007 Elsevier Ltd. All rights reserved. Aziridines are important as well as versatile building blocks used in the synthesis of various natural products and bioactive molecules. The synthetic importance of these molecules is due to their ability to undergo nucleophilic ring opening reactions with a variety of nucleophiles. Nucleophilic ring opening of 2-alkyl-Nactivated aziridines and in situ generated aziridinium ions from non-activated aziridines is known to proceed via an SN2 pathway. Aziridines can readily undergo a formal [3+2] cycloaddition reaction with a range of dipolarophiles leading to five-membered nitrogen-containing heterocycles. BF3ÆOEt2-mediated nucleophilic ring opening or [3+2] cycloaddition of 2-aryl-N-tosylaziridines is known where the reaction is believed to proceed through a stable 1,3-dipolar intermediate. As a result, the enantioselective version of this reaction is not expected to be realized through nucleophilic ring opening of chiral 2-aryl-N-tosylaziridines. In contrast to the earlier reports, we have observed the formation of non-racemic products via nucleophilic ring opening of chiral 2-phenyl-N-tosyl aziridine with various nucleophiles. We have proposed a new mechanism and have shown that the ring opening processes proceed through an SN2-type pathway 7 instead of a 1,3-dipole as invoked earlier in the literature. In continuation of our mecha0040-4039/$ see front matter 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2007.03.042