The use of N-sulfenylimines in the β-lactam synthon method: Staudinger reaction, oxidation of the cycloadducts and ring opening of β-lactams

Selected N-sulfenylimines act as good nucleophilic partners in the Staudinger reaction with methoxy- and benzyloxy-ketenes. The choice of diisopropylethylamine as a non-nucleophilic Lewis base for the generation of ketenes from acid chlorides is a determining factor for the success of the reaction. N-Sulfenyl-β-lactams are obtained in good to excellent yields and with moderate cis/trans diastereoselectivity. Then, they are quantitatively and selectively transformed to N-sulfinyl- or N-sulfonyl-β-lactams, by adjusting the oxidation state of the sulfur atom. The oxidation process induces an inversion of polarity of the nitrogen atom's substituent and allows a subsequent smooth ring opening by reaction of N-thiolated-β-lactams with various nucleophiles. The overall sequence provides straightforward and efficient route to highly functionalized-β-amino acid derivatives.