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

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

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.

• Jezik: Angleški jezik
• Ključne besede: adaptive crystals, asymmetric catalysis, density functional calculations, drug design, fluorine, hydrogenation, kinetic resolution, ruthenium, alcohols, catalysts, crystals, ketones, stereoselectivity
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: Str. 396−404
• Številčenje: Vol. 2, iss. 5
• PID: 20.500.12556/RUL-141984
• UDK: 54
• ISSN pri članku: 2694-247X
• DOI: 10.1021/acsorginorgau.2c00019
• COBISS.SI-ID: 111499267
• Datum objave v RUL: 13.10.2022

Gradivo je del revije

• Naslov: ACS organic & inorganic Au
• Skrajšan naslov: ACS org. inorg. Au
• Založnik: American Chemical Society
• ISSN: 2694-247X
• COBISS.SI-ID: 103423491

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.