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Published on: February 7, 2019
Adamantyl-BOX Ligand Enabling Stereoselective Synthesis of Axially Chiral Aldehydes Bearing Vicinal Stereogenic
Er-Jun Hao1, Xiao-Bo Ding2, Jing-Ran Shan3
1State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, School of Pharmaceutical Sciences, Henan Normal University, Xinxiang, Henan 453007, China.
Abstract:
Biaryl frameworks combining axial and multiple central chiralities are highly valuable in synthesis and drug discovery. However, simultaneous construction of axial and vicinal central chiralities faces severe matching/mismatching limitations. Herein, we describe a dual photoredox/nickel-catalytic system for desymmetrization of biaryl dialdehydes. By employing a bisoxazoline ligand bearing bulky adamantylphenyl side arms, its chiral cavity and distal substituent effects work synergistically to achieve high stereoselectivity, furnishing homoallylic alcohols with up to >20:1 dr and 99% ee. DFT calculations demonstrate that stereoselectivity is predominantly governed by a complex network of noncovalent interactions between the ligand and substrate.
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