Tandem Iridium Catalysis as a General Strategy for Atroposelective Construction of Axially Chiral Styrenes

Abstract

Axially chiral styrenes are of great interest since they may serve as a class of novel chiral ligands in asymmetric synthesis. However, only recently have strategies been developed for their enantioselective preparation. Thus, the development of novel and efficient methodologies is highly desirable. Herein, we reported the first tandem iridium catalysis as a general strategy for the synthesis of axially chiral styrenes enabled by Asymmetric Allylic Substitution-Isomerization (AASI) using cinnamyl carbonate analogues as electrophiles and naphthols as nucleophiles. In this approach, axially chiral styrenes were generated through two independent iridium-catalytic cycles: iridium-catalyzed asymmetric allylic substitution and in situ isomerization via stereospecific 1,3-hydride transfer catalyzed by the same iridium catalyst. Both experimental and computational studies demonstrated that the isomerization proceeded by iridium-catalyzed benzylic C–H bond oxidative addition, followed by terminal C–H reductive elimination. Amid the central-to-axial chirality transfer, the hydroxyl of naphthol plays a crucial role in ensuring the stereospecificity by coordinating with the Ir­(I) center. The process accommodated broad functional group compatibility. The products were generated in excellent yields with excellent to high enantioselectivities, which could be transformed to various axially chiral molecules.

Development of Axially Chiral Styrene-Type Carboxylic Acid Ligands via Palladium-Catalyzed Asymmetric C–H Alkynylation

“…During the past few years, our group has developed a variety of enantioselective C–H functionalizations. , In order to bridge the synthetic gap of axially chiral styrene-type carboxylic acid catalysis, in this work we report a mono- N -protected amino acid (MPAA)-promoted, carboxylate-directed asymmetric C–H alkynylation strategy via palladium catalysis . This transformation exhibited excellent stereocontrol, high efficiency, and mild conditions.…”

Carbene-catalyzed atroposelective synthesis of axially chiral styrenes

“…It is only in recent years that several approaches emerged for asymmetric access to axially chiral aryl-acyclic alkene scaffolds. These remarkable studies include chiral amines catalyzed addition of carbon anions to ynals 33 , Brønsted acids catalyzed addition of nucleophiles (e.g., sulfinic anions, 5H-oxazol-4-ones, and electrorich aromatic units) to in situ generated allenes 34 – 43 , transition metal-catalyzed cross coupling 44 – 46 , and desymmetrization/kinetic resolution strategies (Fig. 1b ) 47 – 51 .…”

Carbene-Catalyzed Atroposelective Synthesis of Axially Chiral Styrenes Bearing Acyclic Alkenes

“…These remarkable studies include chiral amines or Brønsted acids catalyzed addition of nucleophiles to ynals 33 and in situ generated allenes [34][35][36][37][38][39][40][41][42][43] , transition metal-catalyzed cross coupling, [44][45][46] and desymmetrization/kinetic resolution strategies (Fig. 1b).…”