有机催化剂控制的立体选择性大环化反应

Organocatalyst- controlled stereoselective head- to- tail macrocyclizations Jonas W. Rackl, Linus B. Boll, Helma Wennemers* Chiral macrocycles are key to the discovery of new medicines. Their synthesis is, however, challenging and typically requires the often- cumbersome installation of stereochemical features in a linear precursor. In this study, we report a catalyst- controlled stereoselective head- to- tail macrocyclization. The method utilizes a bifunctional peptide catalyst to template the terminal functional groups of the linear precursor, thereby favoring intra- over intermolecular reaction and enabling exquisite control over the stereochemistry of the emerging stereogenic centers. Diverse 12- to 18‐ membered macrocyclic lactones and lactams were obtained from achiral linear precursors. The organocatalyst even dictates the stereochemical outcome upon cyclizing a chiral linear precursor. …