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

• Published in: Angewandte Chemie International Edition 2021-10, Vol.60 (43), p.23187-23192
• Main Authors: Yuan, Wen‐Kui, Shi, Bing‐Feng
• Format: Article
• Language: English
• Subjects: Acetic acid; Aldehyde reductase; Asymmetric synthesis; Asymmetry; binary catalysts; Binary system; chiral phosphoric acid; Cobalt; C−H activation; Enantiomers; enantioselectivity; Phosphoric acid; Reductases; Synthesis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202108853

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. An unprecedented sequential C−H olefination/asymmetric [4+1] spirocyclization under a simple CoII/chiral spiro phosphoric acid (SPA) binary system is reported, providing a straightforward route for the asymmetric synthesis of spiro‐γ‐lactams with high enantioselectivities (up to 98 % ee).