The cycloaddition reactions of fluoro-substituted ketenes and imines (H 2CNH, CH 3CHNH, CH 3OCHNH and NH 2CHNH) leading to 2-azetidinones were studied theoretically using RHF/3-21G. For H 2CNH, CH 3CHNH and CH 3OCHNH the reactions are believed to be non-synchronous and concerted. Four orbitals are involved in these reactions, which are of “2 × [1 + 1]” type. However, in the case of NH 2CHNH the reaction proceeds in a two-step manner. The order of activity of the substituted imines studied is: NH 2CHNH ⪢ CH 3OCHNH ⪢ CH 3CHNH ⪢ H 2CNH. The effect of substituents on the mechanism and activity of these reactions is explained in terms of frontier orbital interactions.