Catalytic Stereoconvergent Synthesis of Homochiral β-CF 3 , β-SCF 3 , and β-OCF 3 Benzylic Alcohols - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue ACS Organic & Inorganic Au Année : 2022

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

Andrej Emanuel Cotman
Pavel Dub
Maša Sterle
Matic Lozinšek
Anamarija Zega
Tihomir Tomašič

Résumé

We describe an efficient catalytic strategy for enantio- and diastereoselective synthesis of homochiral β-CF3, β-SCF3, and β-OCF3 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.
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Dates et versions

hal-03808161 , version 1 (10-10-2022)

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Andrej Emanuel Cotman, Pavel Dub, Maša Sterle, Matic Lozinšek, Jaka Dernovšek, et al.. Catalytic Stereoconvergent Synthesis of Homochiral β-CF 3 , β-SCF 3 , and β-OCF 3 Benzylic Alcohols. ACS Organic & Inorganic Au, 2022, 2 (5), pp.396-404. ⟨10.1021/acsorginorgau.2c00019⟩. ⟨hal-03808161⟩
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