Enantio‐ and Regioconvergent Nickel‐Catalyzed Etherification of Phenols by Allylation to Access Chiral C(sp3)−O Allyl Aryl Ethers

• Published in: Angewandte Chemie International Edition 2024-11, Vol.63 (48), p.e202412181-n/a
• Main Authors: Brösamlen, Daniel, Neb, Daniel, Oestreich, Martin
• Format: Article
• Language: English
• Subjects: Allyl compounds; Allylic Substitution; Aromatic compounds; Asymmetric Catalysis; Catalysis; Chemical reactions; Etherification; Ethers; Nickel; Phenols; Regioselectivity; Room temperature; Silicon
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202412181

An enantio‐ and regioconvergent allylation of phenols under nickel catalysis with an α‐/γ‐regioisomeric mixture of racemic silylated/germylated allylic chlorides is reported. The silyl/germyl group governs the regioselectivity, and the transformation affords enantiomerically enriched unsymmetrical 1,3‐disubstituted allyl aryl ethers with excellent regiocontrol in good yields and excellent enantioselectivities. Notably, no nickel‐mediated C−O bond activation is observed at room temperature. The synthetic value of these densely functionalized silicon‐containing building blocks is demonstrated in a series of chemoselective transformations, including a [3,3]‐sigmatropic rearrangement for the construction of an α‐chiral silane. A nickel‐catalyzed etherification of phenols with regioisomeric mixtures of racemic silylated and germylated allylic chlorides enables the enantio‐ and regioconvergent formation of unsymmetrical 1,3‐disubstituted chiral allylic aryl ethers as a single regioisomer (see Scheme). Key to success is the metalloid moiety governing the regioselectivity, and these highly functionalized allylic ethers can subsequently undergo chemoselective chemical modifications.