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

An unprecedented enantioselective synthesis of spiro-gamma-lactams via a sequential C-H olefination/asymmetric [4+1] spirocyclization under a simple Co-II/chiral spiro phosphoric acid (SPA) binary system is reported. A range of biologically important spiro-gamma-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*, Cp-tBu, or chiral Cp-x) ligated Co-III complexes requiring tedious steps to prepare, cheap and commercially available cobalt(II) acetate tetrahydrate was used as an efficient precatalyst.

Automated summary

An unprecedented enantioselective synthesis of spiro-gamma-lactams was achieved using a simple Co-II/chiral spiro phosphoric acid binary system, resulting in high levels of enantioselectivity. Additionally, a concise synthesis of an aldose reductase inhibitor was successfully carried out under this system.