Catalytic Stereoconvergent Synthesis of Homochiral β-CF 3 , β-SCF 3 , and β-OCF 3 Benzylic Alcohols.

Autor: Cotman AE; Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia., Dub PA; Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States., Sterle M; Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia., Lozinšek M; Jožef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia., Dernovšek J; Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia., Zajec Ž; Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia., Zega A; Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia., Tomašič T; Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia., Cahard D; CNRS UMR 6014 COBRA, Normandie Université, 76821 Mont Saint Aignan, France.
Jazyk: angličtina
Zdroj: ACS organic & inorganic Au [ACS Org Inorg Au] 2022 Oct 05; Vol. 2 (5), pp. 396-404. Date of Electronic Publication: 2022 Jun 08.
DOI: 10.1021/acsorginorgau.2c00019
Abstrakt: 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.
Competing Interests: The authors declare no competing financial interest.
(© 2022 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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