Arylations of Substituted Enamides by Aryl Iodides: Regio- and Stereoselective Synthesis of (Z)-β-Amido-β-Arylacrylates

Abstract

Arylations of substituted enamides by aryl iodides were achieved for the first time via an unusual PdCl2(COD)/Ag3PO4 catalytic system. A broad range of (Z)-β-amido-β-arylacrylates were prepared regio- and stereoselectively in a highly efficient manner.

Palladium‐Catalyzed Base‐Promoted Arylation of Unactivated C(sp3)–H Bonds by Aryl Iodides: A Practical Approach To Synthesize β‐Aryl Carboxylic Acid Derivatives

“…Kinetic isotope experiments [parallel intermolecular kinetic isotope effect (KIE) = 1.28, one‐pot intermolecular KIE = 3.13, intramolecular KIE = 4.04; see the Supporting Information] suggested that cleavage of the β‐C(sp 3 )–H bond of the substrate occurred as part of the reaction pathway but was not the rate‐limiting step . In light of our previous study[8b] and the limited amount of data available, a reaction mechanism was proposed, as shown in Scheme . Complexation of substrate 1 with the palladium catalyst results in the formation of intermediate A , which further undergoes β‐C(sp 3 )–H bond activation under the assistance of CsOAc to give B .…”

“…However, the complexity of natural products can cause issues of chemo‐ or regioselectivity if C–H activation/functionalization takes place. Bile acid derivatives have demonstrated their medicinal applications as FXR agonists in the treatment of dyslipidemia such as nonalcoholic steatohepatitis (NASH), as exemplified by recent global approval of obeticholic acid (Ocaliva) However, to the best of our knowledge, very few β‐aryl bile acid derivative have been reported,[8b] and their pharmacological value as FXR agonists remains valuable to explore. Therefore, we were particularly interested in applying this method to prepare β‐aryl bile acid analogues.…”

“…In our program to develop new C–H activation/C–C bond‐formation reactions, we recently reported a method for the palladium‐catalyzed arylation of β‐C(sp 3 )–H bonds of carboxylic amides by using (diacetoxyiodo)arenes as the arylation reagents. [8b] The application of (diacetoxyiodo)arenes in C(sp 3 )–H bond arylation as arylation reagents was also reported by different groups .…”

“…In our program to develop new C–H activation/C–C bond‐formation reactions, we recently reported a method for the palladium‐catalyzed arylation of β‐C(sp 3 )–H bonds of carboxylic amides by using (diacetoxyiodo)arenes as the arylation reagents. [8b] The application of (diacetoxyiodo)arenes in C(sp 3 )–H bond arylation as arylation reagents was also reported by different groups . Our method operated under the assistance of 8‐aminoquinoline, a removable bidentate directing group that was first introduced by Daugulis in the β‐arylation of carboxylic acid derivatives and subsequently employed in other C–H activation reactions .…”

PdII‐Catalyzed Purine‐Directed Ortho Nitration of 6‐Arylpurines by C(sp2)–H Activation: A Practical Approach to Synthesize 6‐(2‐Nitroaryl)‐Purine Derivatives

“…In a program directed to develop new C–H activation reactions, we have become interested in investigating of ortho nitration of 6‐arylpurines by using purine as intrinsic directing group. If successful, this transformation could produce a variety of 6‐(2‐nitroaryl)‐purine derivatives in a straightforward manner.…”