Dynamic kinetic asymmetric arylation and alkenylation of ketones

Despite the importance of enantioenriched alcohols in medicinal chemistry, total synthesis, and materials science, the efficient and selective construction of enantioenriched tertiary alcohols bearing two contiguous stereocenters has remained a substantial challenge. We report a platform for their p...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2023-02, Vol.379 (6633), p.662-670
Main Authors: Ruan, Lin-Xin, Sun, Bo, Liu, Jia-Ming, Shi, Shi-Liang
Format: Article
Language:English
Subjects:
Alcohols
Carbonyl compounds
Carbonyls
Catalysts
Ketones
Nickel
Nucleophiles
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Summary:Despite the importance of enantioenriched alcohols in medicinal chemistry, total synthesis, and materials science, the efficient and selective construction of enantioenriched tertiary alcohols bearing two contiguous stereocenters has remained a substantial challenge. We report a platform for their preparation through the enantioconvergent, nickel-catalyzed addition of organoboronates to racemic, nonactivated ketones. We prepared several important classes of α,β-chiral tertiary alcohols in a single step with high levels of diastereo- and enantioselectivity through a dynamic kinetic asymmetric addition of aryl and alkenyl nucleophiles. We applied this protocol to modify several profen drugs and to rapidly synthesize biologically relevant molecules. We expect this nickel-catalyzed, base-free ketone racemization process to be a widely applicable strategy for the development of dynamic kinetic processes.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.ade0760