Nucleophilic ring-opening of azetidinium ions: Insights into regioselectivity

Enantiopure azetidinium salts presenting various and representative substitution patterns at C-2, C-3 and C-4 have been prepared by alkylation of the corresponding azetidine with methyl trifluoromethanesulfonate. These compounds were treated with an array of nitrogen (azide anion or benzylamine) and oxygen (acetate anion or alkoxides) nucleophiles which provided interesting insights into the regioselectivity of the ring-opening process. Nucleophilic opening occurred in most cases regioselectively at C-4 with azetidinium ions possessing no substituent at this position. On the other hand, highly regioselective opening at C-2 occurred with trisubstituted azetidinium ions bearing a methyl group at C-4. Experimental selectivities together with DFT calculations have allowed a better understanding of the parameters governing the regioselectivities. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).