Oxidative C-arylation of free (NH)-heterocycles via direct (sp3) C-H bond functionalization.
The development of a new chemical transformation, namely oxidative C-arylation of saturated (NH)-heterocycles, is described. This reaction combines dehydrogenation and arylation in one process, leading to cross-coupling of (NH)-heterocycles and haloarenes. Typical reaction conditions involve heating the reaction partners in anhydrous dioxane at 120-150 degrees C in the presence of RhCl(CO)[P(Fur)3]2 as the catalyst and Cs2CO3 as the base. Addition of tert-butylethylene as the hydrogen acceptor increases the chemical yield by diminishing the dehalogenation pathway. This method demonstrated a good substrate scope, allowing for cross-coupling of a variety of (NH)-heterocycles (e.g., pyrrolidine, piperidine, piperazine, morpholine) and halo(hetero)arenes to afford valuable heterocyclic products in one step. The preliminary mechanistic studies provided some insight regarding the key events in the proposed catalytic cycle, including beta-hydride elimination of an amido rhodium complex and carbometalation of the resulting imine. A large kinetic isotope effect [KIE (kC-H/kC-D) = 4.3] suggests that one or both beta-hydride elimination steps are rate determining. The central role for the phosphine ligand was established in controlling the partitioning between the oxidative C-arylation and N-arylation pathways.
Sezen
Bengü
B
Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA.
Sames
Dalibor
D
D000840:Anisoles / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007462:Iodobenzenes / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D010720:Phosphines / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry; D013237:Stereoisomerism
D000840:Anisoles; D006571:Heterocyclic Compounds; D007462:Iodobenzenes; D009942:Organometallic Compounds; D010720:Phosphines; D011759:Pyrrolidines; C108415:4-iodoanisole; D012238:Rhodium