Direct Enamido C(sp2)−H Diphosphorylation Enabled by a PCET‐Triggered Double Radical Relay: Access to gem‐Bisphosphonates

• Published in: Chemistry : a European journal Vol. 26; no. 24; pp. 5515 - 5521
• Main Authors: Cao, Hao‐Qiang, Liu, Hao‐Nan, Liu, Zhe‐Yuan, Qiao, Bao‐Kun, Zhang, Fa‐Guang, Ma, Jun‐An
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 24.04.2020; Wiley Subscription Services, Inc
• Subjects: Bisphosphonates; Chemistry; Chemistry, Multidisciplinary; enamides; Physical Sciences; radical relay; Science & Technology; silver; synthetic methods; REGIOSELECTIVE PHOSPHONATION; enamides; DRUG-DELIVERY; NITROGEN-CONTAINING BISPHOSPHONATES; H-PHOSPHONATES; ALKYNES; radical relay; BIOLOGICAL EVALUATION; DIPHOSPHATE SYNTHASE; bisphosphonates; silver; BONE; PD(II)-CATALYZED PHOSPHORYLATION; PALLADIUM-CATALYZED PHOSPHONATION; synthetic methods
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202000517

Herein we report a novel and straightforward protocol for the construction of valuable gem‐BPs by means of proton‐coupled electron‐transfer (PCET)‐triggered enamido C(sp2)−H diphosphorylation. This reaction represents a rare example of realizing the challenging double C−P bond formation at a single carbon atom, thus providing facile access to a broad variety of structurally diverse bisphosphonates from simple enamides under silver‐mediated conditions. Initial mechanistic studies demonstrated that the diphosphorylation involves two rounds of PCET‐initiated radical relay process. C−P bond formation: By taking advantage of a PCET‐triggered radical relay process, a new general method to versatile valuable functionalized gem‐bisphosphonates is described (see scheme).