title: Ruthenium-catalyzed α-(hetero)arylation of saturated cyclic amines: reaction scope and mechanism.
abstract: Transition-metal-catalyzed sp(3) C-H activation has emerged as a powerful approach to functionalize saturated cyclic amines. Our group recently disclosed a direct catalytic arylation reaction of piperidines at the α position to the nitrogen atom. 1-(Pyridin-2-yl)piperidine could be smoothly α-arylated if treated with an arylboronic ester in the presence of a catalytic amount of [Ru3(CO)12] and one equivalent of 3-ethyl-3-pentanol. A systematic study on the substrate and reagent scope of this transformation is disclosed in this paper. The effect of substitution on both the piperidine ring and the arylboronic ester has been investigated. Smaller (pyrrolidine) and larger (azepane) saturated ring systems, as well as benzoannulated derivatives, were found to be compatible substrates with the α-arylation protocol. The successful use of a variety of heteroarylboronic esters as coupling partners further proved the power of this direct functionalization method. Mechanistic studies have allowed for a better understanding of the catalytic cycle of this remarkable transformation featuring an unprecedented direct transmetalation on a Ru(II)-H species.
authors.affiliation: Organic Synthesis, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
authors.forename: Aldo
authors.initials: A
authors.lastname: Peschiulli
authors.forename: Veerle
authors.initials: V
authors.lastname: Smout
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Storr
authors.forename: Emily A
authors.initials: EA
authors.lastname: Mitchell
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Eliáš
authors.forename: Wouter
authors.initials: W
authors.lastname: Herrebout
authors.forename: Didier
authors.initials: D
authors.lastname: Berthelot
authors.forename: Lieven
authors.initials: L
authors.lastname: Meerpoel
authors.forename: Bert U W
authors.initials: BU
authors.lastname: Maes
mesh_terms: D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*
chemical_list: C583635:1-(pyridin-2-yl)piperidine; D000588:Amines; D010880:Piperidines; D011725:Pyridines; D012428:Ruthenium
keywords: CH activation; homogeneous catalysis; hydrogen; nitrogen heterocycles; ruthenium