Synthesis of sp3-rich chemical libraries based upon 1, 2-diazetidines. (22nd January 2021)

• Record Type: Journal Article
• Authors: Dean, Conor; Roesner, Stefan; Rajkumar, Sundaram; Clarkson, Guy J.; Jones, Matthew; Shipman, Michael
• Is Part Of: Tetrahedron. Volume 79(2021)
• Publication Date: 2021-01-22
• Subjects: sp3-rich scaffold -- Chemical library -- Hydrazine -- 1, 2-Diazetidine -- Epoxide opening; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2020.131836
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: A strategy for the creation of sp 3 -rich, non-planar scaffolds for drug discovery is described. Stereocontrolled ring opening of homochiral 1, 2-epoxides by hydrazine monohydrate followed by selective protection of both nitrogen atoms and Mitsunobu ring closure gives differentially protected, enantiomerically pure 1, 2-diazetidines (up to 98% ee) bearing a variety of C-3 substituents. Iterative C–N functionalization at the two nitrogen atoms using a range of chemistries and coupling partners produces a 1, 2-diazetidine based chemical library. Crystallographic data confirm that these frameworks display significant sp 3 -character with the nitrogen substituents adopting an anti -configuration. Graphical abstract: Image 1