Synthesis of novel chiral spiro-β-lactams from nitrile oxides and 6-(Z)-(benzoylmethylene)penicillanate: batch, microwave-induced and continuous flow methodologies

Abstract

The first examples of the diastereoselective 1,3-dipolar cycloaddition reaction of nitrile oxides and 6-alkylidene penicillanates leading to chiral spiroisoxazoline-penicillanates are reported. The synthesis of this new type of penicillanate involved the selective generation of two consecutive stereogenic centers, including a quaternary chiral center. Furthermore, the present work also describes the outcomes of these 1,3-dipolar cycloaddition reactions under three distinct reaction conditions (conventional heating, microwave irradiation and continuous flow). The successful use of the continuous flow technique as well as the proper selection of the reaction media allowed the development of a sustainable route to chiral spiroisoxazoline-penicillanates.