Copper(I)-Catalyzed Kinugasa Reactions in an Undergraduate Organic Chemistry Laboratory

Abstract

A β-lactam, the core structure unit of clinically important antibiotics such as penicillin and cephalosporin, is one of the most commonly encountered four-membered heterocycles in organic chemistry and is widely used in medicine and biochemistry. The Kinugasa reaction, a copper(I)-catalyzed cycloaddition of a terminal alkyne with a nitrone, is a straightforward and atom economic approach to 2,3-disubstituted β-lactams. This paper describes a comprehensive chemistry experiment involving the Kinugasa reaction in an advanced undergraduate organic chemistry laboratory course. Undergraduate students perform the Kinugasa reaction on the benchtop and isolate and characterize the β-lactam product. An understanding of this named reaction and the connection of organic chemistry with medicinal chemistry are specially emphasized in the class. Several modern chemistry concepts that are missing from traditional organic courses such as β-lactam chemistry, [3 + 2] cycloaddition, atom economy, and the important role of transition metal catalysis in organic reactions are introduced to students in this course.