Dynamic Kinetic Resolution for the Catalytic Asymmetric Total Synthesis of Antithrombotic Agents M58163 and M58169

Abstract

Dynamic kinetic resolution is one of the most synthetically useful phenomena for asymmetric synthesis. Dynamic kinetic resolution for the catalytic asymmetric synthesis of a spiroA-one scaffold with a lanthanum-linked BINOL complex is described. It is also clarified that starting materials, diamine 1 and keto ester 2, play important roles not only as substrates but also as additives to modify an active species of the lanthanum complex. The catalytic asymmetric total syntheses of our antithrombotic agents M58163 and M58169 have thus been achieved via dynamic kinetic resolution.

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…Saitoh, Mikami, and co-workers completed the asymmetric total syntheses of M58163 ( 303 ) and M58169 ( 304 ), both of which display antithrombotic activity (Scheme ). Access to their imidazopyrazinone core ( 301 ) was achieved using a lanthanum-catalyzed asymmetric cascade cyclization proceeding through racemic aminal 302 . , Mechanistic studies revealed that the aminal is formed reversibly, with enantioselection occurring during the La-catalyzed amide bond-forming step. A survey of various lanthanide metal complexes revealed that the La-linked BINOL complex 294 (Figure ) gave the best yield and selectivity.…”