From Peripheral Stereogenic Center to Axial Chirality: Synthesis of 3‐Arylthiophene Atropisomers

Abstract

A practical synthesis of axially chiral biaryls via chirality transfer from peripheral stereogenic carbon centers is reported. In contrast to the traditional aromatization process of a non-aromatic structure with ipso stereogenic centers, this method is based on a Pd-catalyzed carbon-carbon bond cleavage/ring-opening reaction of optically active 8H-indenothiophen-8-ols with an achiral ligand, enabling synthesis of highly functionalized 3-arylthiophene atropisomers in high enantioselectivity.

A Chiral Relay Race: Stereoselective Synthesis of Axially Chiral Biaryl Diketones through Ring-Opening of Optical Dihydrophenan-threne-9,10-diols

“…In 2022, we observed that optically active 8 H -indeno [1,2-c]thiophen-8-ols would undergo a stereoselective ring-opening reaction with an achiral palladium complex, resulting in the formation of axially chiral biaryls ( Scheme 1 b) [ 34 , 35 ]. This chirality relay is based on the fact that one of the aryl rings would approach the Pd atom, ultimately resulting in the construction of axial chirality.…”

Kinetic Resolution of Helicenols via Palladium-Catalyzed Atroposelective C–C Bond Cleavage/Ring-Opening Reaction

“…Unfortunately, endeavors for the preparation of enantiopure VI were unsuccessful: the Pd-catalyzed carbonylation/cyclization of enantiopure IV at 120 °C gave a 45% yield of intermediate V but with a significantly eroded enantiomeric excess (ee) value. Inspired by the aforementioned results and our previous work, we present here a palladium-catalyzed kinetic resolution of helicenols. This method allows for the concurrent generation of chiral helicenols and sterically hindered biaryl atropisomers (Scheme c).…”

Synthesis of Atropisomers with Biaryl and Vinylaryl Chirality via Pd-Catalyzed Point-to-Axial Chirality Transfer Ring-Opening Reaction

“…Recently, we have developed a Pd-catalyzed kinetic resolution reaction of 8 H -indeno­[1,2- c ]­thiophen-8-ols via stereoselective ring opening . Notably, in addition, the optically active 8 H -indeno­[1,2- c ]­thiophen-8-ols obtained at the kinetic resolution mentioned above would undergo Pd-catalyzed ring-opening reaction with nearly full point to axial chirality transfer in the presence of an achiral phosphine ligand (Scheme c) . Taking advantage of this chirality transfer process, we are keen to develop a Pd-catalyzed domino cyclization reaction/ring-opening reaction to construct atropisomers with multiple chiral axes, such as vinyl–aryl and aryl–aryl axes (Scheme d).…”