Remarkable Effects of Lone Pair—Lone Pair Interactions on the Extremely Stereoselective [2 + 2] Cycloaddition of Azidoketene to Chiral 3-Imino-β-lactams

The stereoselective [2 + 2] cycloadditions of azidoketene to cis-3-imino-β-lactams 1, 2, and 3, trans-3-imino-0-lactam 4, and rts-3-iminoazetidine 5 were carried out. It was found that the reactions of 1, 2, and 3 proceeded with <99.5% stereoselectivity to give bis-β-lactams 9, 14, and 19, respectively. The reaction of 4 gave a bis-β-lactam 20 with 62% de, and the reaction of 5 gave a β-lactamazetidine 21 with 32% de inducing the asymmetry in the opposite direction. These results clearly indicate that, in addition to the conventional steric effects, the lone pair-lone pair interaction of β-lactam oxygen with the intermediate betaine's oxygen is the crucial factor for the extremely stereoselective [2 + 2] cycloaddition of azidoketene to 1, 2, and 3. Possible mechanisms for these stereoselective [2 + 2] cycloadditions are proposed. The X-ray crystal structure of 3a and the calculated energy-minimum conformations of 3a, 4, and 5 withmodel-mm2-rotochemprograms are provided.