Achiral Additives for Enhancing the Stereoselectivity of Cycloadditions

Significance

The stereoselectivity of Lewis acid catalyzed Diels-Alder and nitrone cycloadditions was enhanced by the addition of a variety of achiral additives. In some cases, using Mg(II), Ni(II), Fe(II), Co(II), and Zn(II), dramatic improvements in enantio­selectivity were observed when additive A or B were used. It was also shown that the additive can be modified by altering the size of nitrogen substituents to enhance its effectiveness. The authors propose that the chiral ligand still dictates the facial selectivity, but the additive improves the rigidity of the transition state, and brings the chiral elements closer to the reactive site, greatly enhancing the stereoselectivity.