Highly diastereoselective Mannich reaction between 3‑amino oxindole Schiff base and oxindole ketimines–Direct and effective preparation of adjacent tetrasubstituted 3,3′-bisoxindole protected diamines

Abstract

A highly diastereoselective (all > 20:1 dr) and effective (1 mol% cat) new Mannich reaction between 3‑amino oxindole Schiff base and oxindole ketimines promoted by catalytic DMAP under mild conditions has been disclosed. Highly steric 3,3′-bisoxindole protected diamines with adjacent tetrasubstituted stereocenters were conveniently and directly obtained in high yields and excellent diastereoselectivities (all > 20:1 dr) within a few minutes. A further preparation of the adjacent tetrasubstituted 3,3′-bisoxindole free diamines by general deprotection lead to the collapse of the diamine scaffold. A typical scale-up preparation, partial hydrolysis of the product and subsequent transformations of the resulting free monoamine with phenylcyanate and phenylisothiocyanate was smoothly performed to form new bisoxindole ureas and thioureas. Our protocol and the easily obtained new diversity of bisoxindoles may find potential pharmaceutical and catalytic applications.