title: N-Heterocyclic Carbene Ligand-Enabled C(sp(3))-H Arylation of Piperidine and Tetrahydropyran Derivatives.
abstract: Pd(II)-catalyzed C(sp(3))-H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N-heterocyclic carbene (NHC) ligand. A C(sp(3))-H insertion step by the Pd(II)/NHC complex in the absence of ArI is demonstrated experimentally for the first time. Experimental data suggests that the previously established NHC-mediated Pd(0)/Pd(II) catalytic manifold does not operate in this reaction. This transformation provides a new approach for diversifying pharmaceutically relevant piperidine and tetrahydropyran ring systems.
authors: Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors: Shengqing
authors: S
authors: Ye
authors: Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors: Weibo
authors: W
authors: Yang
authors: Medicinal Chemistry, Vertex Pharmaceuticals, 11010 Torreyana Rd, San Diego, CA, 92121, USA.
authors: Timothy
authors: T
authors: Coon
authors: Medicinal Chemistry, Vertex Pharmaceuticals, 11010 Torreyana Rd, San Diego, CA, 92121, USA.
authors: Dewey
authors: D
authors: Fanning
authors: Medicinal Chemistry, Vertex Pharmaceuticals, 11010 Torreyana Rd, San Diego, CA, 92121, USA.
authors: Tim
authors: T
authors: Neubert
authors: Medicinal Chemistry, Vertex Pharmaceuticals, 11010 Torreyana Rd, San Diego, CA, 92121, USA. Dean_Stamos@vrtx.com.
authors: Dean
authors: D
authors: Stamos
authors: Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. yu200@scripps.edu.
authors: Jin-Quan
authors: JQ
authors: Yu
mesh_terms: D002384:Catalysis; D008024:Ligands; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D011714:Pyrans / Q000737:chemistry*
chemical_list: D008024:Ligands; D010880:Piperidines; D011714:Pyrans; C030011:carbene; D008697:Methane
keywords: C−H activation; N-heterocyclic carbenes; arylation; heterocycles; palladium