Asymmetric Construction of an Aryl‐Alkene Axis by Palladium‐Catalyzed Suzuki–Miyaura Coupling Reaction

Abstract

The application of Suzuki-Miyaura coupling reaction to forge the atropisomeric biaryls has seen remarkable progress but exploration of this chemistry to directly forge chiral C(aryl)-C(alkene) axis is underdeveloped. The replacement of arene substrates by alkenes intensifies the challenges in terms of reactivity, configurational atropostability of product and selectivity control. By meticulous ligand design and fine-tuning of reaction parameters, we identified a highly active 3,3'triphenylsilyl-substituted phosphite ligand to realize arene-alkene Suzuki-Miyaura coupling of hindered aryl halides and vinyl boronates under very mild conditions. The axially chiral acyclic aryl-alkenes were generated in commendable efficiency, enantioselectivity and E/Z selectivity.

Enantioselective Access to Triaryl-2-pyrones with Monoaxial or Contiguous C–C Diaxes via Oxidative NHC Catalysis

“…Axially chiral compounds have played an essential role as chiral ligands and catalysts in asymmetric synthesis. , This class of molecules is widely found in numerous pharmaceutical agents and natural products . Out of different axially chiral structures, substituted biaryls ( A and B , Scheme a) have been extensively developed and applied. − More recently, other atropisomers including alkenes and aryl amides ( C and D , Scheme a) have also been under active investigation. − However, these studies mainly focused on the preparation of atropisomers with a single stereogenic axis. Methods to assemble axially chiral molecules with more than one stereogenic axis ( E and F , Scheme a) have rarely been reported, owing to the formidable challenges involved in the assembly of multiple stereogenic axes with high enantiocontrol.…”

Transition-metal-catalyzed atroposelective synthesis of axially chiral styrenes

“…Later in 2022, Tan, Zhang, Yu and co-workers also reported an atroposelective construction of open-chain aryl-alkene atropisomers via enantioselective Suzuki–Miyaura cross-coupling (Scheme 5). 23 With the absence of weak coordination from the ortho -ether group and π–π stacking from the aryl rings on the substrates, it becomes more difficult to control atroposelectivity. A beneficial correlation was observed between enantioselectivity and the steric bulk of C2-/C7-substituted naphthalene halides.…”

Application of Palladium Single Atoms in C−C Coupling Reactions of Pharmaceutical Synthesis

“…In organic reactions, Suzuki cross-coupling of aryl halogenated hydrocarbons combined with aryl boronic compounds is one of the most effective methods for the formation of carbon-carbon bonds (C-C). [1,2] As a result, it has found extensive use in the pharmaceutical, pesticide chemicals, and fine chemical synthesis industries. Palladium is the most commonly used catalyst for Suzuki cross-coupling reaction.…”