Expedient Synthesis of Axially and Centrally Chiral Diaryl Ethers via Cobalt-Catalyzed Photoreductive Desymmetrization

Axially chiral diaryl ethers make up a unique class of atropisomers bearing restricted rotation about the C–O bond. Methods for the expedient synthesis of axially chiral diaryl ether-based structures have been largely underdeveloped. Herein, we developed an efficient metal-catalyzed desymmetrization strategy to unveil the formation of axially and centrally dual chiral diaryl ethers in high diastereo- and enantioselectivity. The protocol leverages cobalt-catalyzed photoreductive enantioselective couplings of dialdehyde and alkyne to deliver dual stereogenicity, and the diaryl ether scaffold is equipped with useful synthetic handles including formyl, hydroxyl, and allyl groups, as has been demonstrated in the synthesis of a chiral carboxylic acid as a potential chiral ligand in asymmetric catalysis

Expedient Synthesis of Axially and Centrally Chiral Diaryl Ethers via Cobalt-Catalyzed Photoreductive Desymmetrization

Axially chiral diaryl ethers make up a unique class of atropisomers bearing restricted rotation about the C–O bond. Methods for the expedient synthesis of axially chiral diaryl ether-based structures have been largely underdeveloped. Herein, we developed an efficient metal-catalyzed desymmetrization strategy to unveil the formation of axially and centrally dual chiral diaryl ethers in high diastereo- and enantioselectivity. The protocol leverages cobalt-catalyzed photoreductive enantioselective couplings of dialdehyde and alkyne to deliver dual stereogenicity, and the diaryl ether scaffold is equipped with useful synthetic handles including formyl, hydroxyl, and allyl groups, as has been demonstrated in the synthesis of a chiral carboxylic acid as a potential chiral ligand in asymmetric catalysis

<i>O</i>‑Allylhydroxyamine: A Bifunctional Olefin for Construction of Axially and Centrally Chiral Amino Alcohols via Asymmetric Carboamidation

Difunctionalization of olefins offers an attractive approach to access complex chiral structures. Reported herein is the design of N-protected O-allylhydroxyamines as bifunctional olefins that undergo catalytic asymmetric 1,2-carboamidation with three classes of (hetero)arenes to afford chiral amino alcohols via C–H activation. The CC bond in O-allylhydroxyamine is activated by the intramolecular electrophilic amidating moiety as well as a migrating directing group. The asymmetric carboamidation reaction pattern depends on the nature of the (hetero)arene reagent. Simple achiral (hetero)arenes reacted to give centrally chiral β-amino alcohols in excellent enantioselectivity. The employment of axially prochiral or axially racemic heteroarenes afforded amino alcohols with both axial and central chirality in excellent enantio- and diastereoselectivity. In the case of axially racemic heteroarenes, the coupling follows a kinetic resolution pattern with an s-factor of up to >600. A nitrene-based reaction mechanism has been suggested based on experimental studies, and a unique mode of induction of enantio- and diastereoselectivity has been proposed. Applications of the amino alcohol products have been demonstrated

A Stereodivergent–Convergent Chiral Induction Mode in Atroposelective Access to Biaryls via Rhodium-Catalyzed C–H Bond Activation

Understanding the reaction mechanisms, particularly the chiral induction mode, is critical for the development of new asymmetric catalytic reactions. Rhodium­(III)-catalyzed C–H activation en route to atroposelective [4 + 2] annulative coupling with α-diazo β-ketoesters has been realized, affording axially chiral phenanthrenes in good to excellent enantioselectivity. A combination of experimental and computational studies revealed a nontraditional stereodivergent–convergent chiral induction mode. The reaction proceeded with a rhodafluorene intermediate, followed by competitive, constructive, and stereodivergent migratory insertions of the two Rh–C­(aryl) bonds into the carbene species to give β-ketoester intermediates. Then, the other Rh–C­(aryl) bond migratorily inserts into the ketone carbonyl group. Following this stereodetermining carbonyl insertion, an ester-chelated rhodium­(III) alkoxide species bearing two poorly controlled chiral centers and a well-controlled C­(sp2)–C­(sp3) chiral axis is generated. The final product is delivered via stereoconvergent elimination of a rhodium­(III) species with retention of the well-controlled axial chirality and with loss of the central chirality