Intramolecular C–H Amination Reaction Provides Direct Access to 1, 2‐Disubstituted Diamondoids. Issue 28 (20th August 2015)

• Record Type: Journal Article
• Authors: Hrdina, Radim; Metz, Fabian M.; Larrosa, Marta; Berndt, Jan‐Philipp; Zhygadlo, Yevgeniya Y.; Becker, Sabine; Becker, Jonathan
• Is Part Of: European journal of organic chemistry. Issue 28(2015)
• Page Start: 6231
• Page End: 6236
• Publication Date: 2015-08-20
• Subjects: Synthetic methods -- C–H activation -- Insertion -- Amination -- Diamondoids -- Medicinal chemistry; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201500691
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: We present a new approach to disubstituted diamondoids from corresponding carboxylic acids. A dirhodium‐acetate‐catalyzed (1 mol‐%) nitrene insertion reaction of sulfamides was, for the first time, applied to intramolecular C–H functionalization reactions of rigid tricyclic frameworks. This straightforward approach enables the effective and regioselective synthesis of a variety of diamondoid‐based cyclic sulfamidates, which are synthetically valuable building blocks. Reductive deprotection of the sulfamidate moiety leads to corresponding 1, 3‐amino alcohol derivatives. Oxidation of the sulfamidate moiety by KMnO4 provides access to 1, 3‐keto alcohols or imines. Finally, we report the synthesis of Vildagliptin ® analogues as new antidiabetic drug candidates (DPP‐4 inhibitors). Abstract : Intramolecular dirhodium‐acetate‐catalyzed (1 mol‐%) nitrene insertion reactions provide direct access to 1, 2‐disubstituted diamondoids. This approach was applied to the synthesis of Vildagliptin ® (DPP‐4 inhibitor) analogues.