Synthesis of Chiral Spirolactams via Sequential C-H Olefination/Asymmetric [4+1] Spirocyclization under a Simple CoII /Chiral Spiro Phosphoric Acid Binary System.

Abstract

An unprecedented enantioselective synthesis of spiro-γ-lactams via a sequential C-H olefination/asymmetric [4+1] spirocyclization under a simple CoII /chiral spiro phosphoric acid (SPA) binary system is reported. A range of biologically important spiro-γ-lactams are obtained with high levels of enantioselectivity (up to 98 % ee). The concise, asymmetric synthesis of an aldose reductase inhibitor was successfully achieved. Notably, contrast to previous reports that relied on the use of cyclopentadienyl or its derivatives (achiral Cp*, CptBu , or chiral Cpx ) ligated CoIII complexes requiring tedious steps to prepare, cheap and commercially available cobalt(II) acetate tetrahydrate was used as an efficient precatalyst.