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. 2025 Apr 18;90(15):5120-5124.
doi: 10.1021/acs.joc.4c02996. Epub 2025 Apr 9.

Chemoenzymatic Dynamic Kinetic Resolution of Atropoisomeric 2-(Quinolin-8-yl)benzylalcohols

Juan M Coto-Cid  1 , Valentín Hornillos  1 , Rosario Fernández  1 , José M Lassaletta  2 , Gonzalo de Gonzalo  1
Affiliations

Chemoenzymatic Dynamic Kinetic Resolution of Atropoisomeric 2-(Quinolin-8-yl)benzylalcohols

Juan M Coto-Cid et al. J Org Chem. .

Abstract

The chemoenzymatic dynamic kinetic resolution of 2-(quinolin-8-yl)benzylalcohols using a combination of lipases and ruthenium catalysts is described. While CalB lipase performs highly selective enzymatic kinetic resolution, the combination with Shvo's or Bäckvall's catalysts promotes atropisomerization of the substrate via the reversible formation of configurationally labile aldehydes, thereby enabling a dynamic kinetic resolution. This synergistic approach was applied to the synthesis of a variety of heterobiaryl acetates in excellent yields and enantioselectivities.

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Figures

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1. Dynamization Strategy via Transient Lewis Acid–Lewis Base Interactions
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2. Chemoenzymatic Dynamic Resolutions with Lipases
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3. KR of Racemic Heterobiaryl Alcohols (±)-1a–i (0.05 mmol) Catalyzed by CalB (15 mg) in CPME (2 mL) in the Presence of Vinyl Acetate (0.15 mmol) as the Acyl Donor
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4. Chemoenzymatic DKR of Racemic Heterobiaryl Alcohols (±)-1a–i (0.1 mmol) using CalB (30 mg) and Shvo’s Catalyst (2 mol %)
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