Rhodium-Catalyzed C–H/C–H Cross Coupling of Benzylthioethers or Benzylamines with Thiophenes Enabled by Flexible Directing Groups

Reported herein is an efficient synthetic protocol to ortho-functionalized 2-aryl thiophenes via Rh­(III)-catalyzed C–H/C–H cross coupling of benzylthioethers or benzylamines with thiophenes. Both ortho- and meta-substituted benzylthioethers give monoheteroarylated products, while ortho-unhindered substrates mainly provide diheteroarylated benzylthioethers. The C–H/C–H cross coupling of benzylamines with thiophenes exclusively generates diheteroarylated benzaldehydes. Mechanistic investigation discloses a three-step tandem process involving the ortho-C–H diheteroarylation of benzylamine, the oxidation of benzylamine to imine, and the hydrolysis of imine to aldehyde.