Palladium‐Catalyzed Cascade sp² C−H Functionalization/Intramolecular Asymmetric Allylation: From Aryl Ureas and 1,3‐Dienes to Chiral Indolines

Abstract

A chiral Pd -catalyzed cascade sp C-H functionalization/intramolecular asymmetric allylation reaction is reported. A new chiral sulfoxide-oxazoline (SOX) ligand bearing single chiral center on the sulfur was identified as the optimal ligand for the reaction, being efficient both in the C-H cleavage step and the stereocontrol of the allylation step. The broad scope of this method with respect to aryl ureas and 1,3-dienes enables the rapid construction of valuable chiral indoline derivatives with high yields and enantioselectivities (up to 99 % yield, up to 95:5 e.r.).

Palladium‐Catalyzed Asymmetric Aminohydroxylation of 1,3‐Dienes

“…As such, the palladium catalyst is required to be multifunctional;i ts hould efficiently and regioselectively promote the first step and also provide high stereocontrol for the asymmetric allylation. [15,16] Inspired by the palladium-catalyzed non-asymmetric 1,2-diamination reaction of 1,3-dienes with N-protected o-phenylendiamines reported by Zhang and co-workers, [16g] we initiated our investigation using isoprene 1a and N-tosyl-2-aminophenol 2a as the model substrates (Table 1). [15,16] Inspired by the palladium-catalyzed non-asymmetric 1,2-diamination reaction of 1,3-dienes with N-protected o-phenylendiamines reported by Zhang and co-workers, [16g] we initiated our investigation using isoprene 1a and N-tosyl-2-aminophenol 2a as the model substrates (Table 1).…”

“…[15,16] Inspired by the palladium-catalyzed non-asymmetric 1,2-diamination reaction of 1,3-dienes with N-protected o-phenylendiamines reported by Zhang and co-workers, [16g] we initiated our investigation using isoprene 1a and N-tosyl-2-aminophenol 2a as the model substrates (Table 1). Chiral sulfoxide oxazoline ligands,w hich have been successfully applied in an umber of Pd II -catalyzed asymmetric transformations, [15,18] gave poor results (entries 5-6). Encouragingly,t he racemic reaction indeed gave rise to am ixture of 3a and 4a in 75 %a nd 10 %y ields, respectively,thus implying that the aminopalladation is more favored than the oxopalladation (entry 1).…”

“…Encouragingly,t he racemic reaction indeed gave rise to am ixture of 3a and 4a in 75 %a nd 10 %y ields, respectively,thus implying that the aminopalladation is more favored than the oxopalladation (entry 1). We reasoned that MeCN might prevent the coordination of chiral ligands to the palladium center, thus leading to poor enantioselectivity.Amore detailed solvent screening revealed non-polar aromatic solvents to be suitable media (entries [14][15][16]. However,ageneral and severe decline in catalytic activity was observed after the addition of different types of ligands.Electron-poor pyridine oxazoline type ligands L1-L3,w hich are frequently used in asymmetric Wacker-type reactions, [17] rendered the reaction completely unproductive (entries 2-4).…”

Palladium‐Catalyzed Asymmetric Aminohydroxylation of 1,3‐Dienes

“…Because of these difficulties,e xamples describing the Pd II -catalyzed asymmet- ric difunctionalization of 1,3-dienes compared to those that make use of Pd 0 catalysis [14] are far less reported. [15,16] Inspired by the palladium-catalyzed non-asymmetric 1,2-diamination reaction of 1,3-dienes with N-protected o-phenylendiamines reported by Zhang and co-workers, [16g] we initiated our investigation using isoprene 1a and N-tosyl-2-aminophenol 2a as the model substrates (Table 1). At the outset, the reaction was performed in the presence of 10 mol %o f Pd(OAc) 2 at 70 8 8Cf or 20 hours under the atmosphere of oxygen (1 atm).…”

“…However,ageneral and severe decline in catalytic activity was observed after the addition of different types of ligands.Electron-poor pyridine oxazoline type ligands L1-L3,w hich are frequently used in asymmetric Wacker-type reactions, [17] rendered the reaction completely unproductive (entries [2][3][4]. Chiral sulfoxide oxazoline ligands,w hich have been successfully applied in an umber of Pd II -catalyzed asymmetric transformations, [15,18] gave poor results (entries 5-6). In the case of L4,p oor regioselectivity and no stereocontrol were observed (entry 5).…”