Catalytic Synthesis of Atropisomeric o-Terphenyls with 1,2-Diaxes via Axial-to-Axial Diastereoinduction

Abstract

Herein, we report a modular and convergent strategy for the assembly of atropisomeric o-terphenyls with 1,2-diaxes via palladium/chiral norbornene cooperative catalysis and axial-to-axial diastereoinduction. Readily available aryl iodides, 2,6-substituted aryl bromides, and potassium aryl trifluoroborates are used as the building blocks, laying the foundation for diversity-oriented synthesis of these scaffolds (46 examples). Other features include the unique axial-to-axial diastereoinduction mode, construction of two axes in a single operation, and step economy. DFT calculations are performed to rationalize the axial-to-axial diastereoinduction process. Synthetic utilities of this method in preparation of atropisomeric oligophenyls, chiral catalysts, and ligands are demonstrated.

Chiral Selenide/Achiral Sulfonic Acid Cocatalyzed Atroposelective Sulfenylation of Biaryl Phenols via a Desymmetrization/Kinetic Resolution Sequence

“…It is noteworthy that compounds containing multiple stereogenic axes are becoming increasingly important in catalysis, medicinal chemistry, and materials science . However, catalytic asymmetric methods to synthesize this type of compound are relatively rare . Consequently, we turned our attention to forming compounds having two stereogenic axes (Scheme ).…”

Enantioselective Synthesis of Both Axially and Planar Chiral Ferrocenes via Axial-to-Planar Diastereoinduction

“…12 Then, the group used this method to synthesize biaxially chiral compounds. 13 Significant progress has been made in the synthesis of compounds with axial or planar chirality, 14 but the synthesis of molecules with both axial and planar chirality has not been well explored. 15 Herein, we first realize a strategy involving palladium/chiral norbornene cooperative catalysis and axial-to-planar diastereoinduction in this domino process of the Catellani reaction, followed by C(sp 2 )−H activation, to construct compounds with both axial and planar chirality (Figure 1C).…”

“…Immediately afterward, Zhou’s group used palladium/chiral norbornane cooperative catalysis to synthesize axially chiral compounds . Then, the group used this method to synthesize biaxially chiral compounds . Significant progress has been made in the synthesis of compounds with axial or planar chirality, but the synthesis of molecules with both axial and planar chirality has not been well explored .…”

Enantioselective and Diastereoselective C–H Alkylation of Benzamides: Synergized Axial and Central Chirality via a Single Stereodetermining Step

“…In these systems, unsaturated reagents such as olefins, alkynes, enynes, allenes, diazo reagents, and imides have been often employed as the coupling reagents for construction of chiral centers, with C–H activation, migratory insertion, or reductive elimination being enantio-determining. On the other hand, axially chiral arenes have also been accessed via dynamic kinetic resolution of a preformed axis , or by creation of a new chiral axis. , Despite the progress, most of the asymmetric C–H activation systems generate only one chiral element (center or axis), and construction of both central and axial chirality via a single catalytic process is rare. , …”