ABSTRACT
Michael addition reaction was originally defined as the base-catalyzed addition of an active methylene compound (e.g., malonic ester) to an activated unsaturated compound such as an α,β-unsaturated ketone. There is a broad definition for the Michael reaction today as the conjugate addition of a nucleophile as across double bonds conjugated with an electron-withdrawing group [1]. Michael additions are of great importance in biochemistry and molecular biology for the chemical modification of proteins and for the manufacture of antibody–drug conjugates as well as three-dimensional matrices such as hydrogels. N-ethylmaleimide is the most extensively used reagent for the Michael addition modification of thiol groups where it serves as a Michael acceptor with the thiolate serving as the Michael donor.
