Catalytic stereoconvergent synthesis of homochiral β‑CF$_3$, β‑SCF$_3$, and β‑OCF$_3$ benzylic alcohols

Cotman, Andrej Emanuel (author), Dub, Pavel A. (author), Sterle, Maša (author), Lozinšek, Matic (author), Dernovšek, Jaka (author), Zajec, Živa (author), Zega, Anamarija (author), Tomašič, Tihomir (author), Cahard, Dominique (author)

We describe an efficient catalytic strategy for enantio- and diastereoselective synthesis of homochiral β-CF$_3$, β-SCF$_3$, and β-OCF$_3$ benzylic alcohols. The approach is based on dynamic kinetic resolution (DKR) with Noyori−Ikariya asymmetric transfer hydrogenation leading to simultaneous construction of two contiguous stereogenic centers with up to 99.9% ee, up to 99.9:0.1 dr, and up to 99% isolated yield. The origin of the stereoselectivity and racemization mechanism of DKR is rationalized by density functional theory calculations. Applicability of the previously inaccessible chiral fluorinated alcohols obtained by this method in two directions is further demonstrated: As building blocks for pharmaceuticals, illustrated by the synthesis of heat shock protein 90 inhibitor with in vitro anticancer activity, and in particular, needle-shaped crystals of representative stereopure products that exhibit either elastic or plastic flexibility, which opens the door to functional materials based on mechanically responsive chiral molecular crystals.

• Language: English
• Keywords: adaptive crystals, asymmetric catalysis, density functional calculations, drug design, fluorine, hydrogenation, kinetic resolution, ruthenium, alcohols, catalysts, crystals, ketones, stereoselectivity
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: Str. 396−404
• Numbering: Vol. 2, iss. 5
• PID: 20.500.12556/RUL-141984
• UDC: 54
• ISSN on article: 2694-247X
• DOI: 10.1021/acsorginorgau.2c00019
• COBISS.SI-ID: 111499267
• Publication date in RUL: 13.10.2022

Record is a part of a journal

• Title: ACS organic & inorganic Au
• Shortened title: ACS org. inorg. Au
• Publisher: American Chemical Society
• ISSN: 2694-247X
• COBISS.SI-ID: 103423491

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• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.