The Malcolmson lab has discovered a reductive coupling of azatrienes and ketones for the Z-selective synthesis of allylic 1,2-amino tertiary alcohols. The strategy, developed by a team that was spearheaded by graduate student Jiaqi Zhu, provides an aminoallylation approach to this valuable pharmacophore that greatly expands upon the chemical space that is accessible for this moiety. The reaction is a rare example of a catalytic carbonyl allylation that forms a Z-alkene and two stereogenic centers and is the first that utilizes a ketone electrophile. Transformations of the products illustrate the synthetic potential of this method through diastereoselective reactions of the alkene and formation of heterocyclic structures. The anti-products obtained in the copper-catalyzed reaction may be converted to syn-amino alcohols in one step, giving facile access to either product diastereomer. Density functional theory (DFT) calculations illustrate the origin of Z-selectivity and of the major stereoisomer generated, revealing Curtin–Hammett kinetics are likely operative in the system. Read more about this method in The Journal of the American Chemical Society.
Chemistry
