Isothiourea-Catalyzed Atropselective Acylation of Biaryl Phenols via Sequential Desymmetrization/Kinetic Resolution.

Autor: Munday ES; EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK., Grove MA; Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR, 97331, USA., Feoktistova T; Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR, 97331, USA., Brueckner AC; Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR, 97331, USA., Walden DM; Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR, 97331, USA., Young CM; EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK., Slawin AMZ; EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK., Campbell AD; Pharmaceutical Technology and Development, AstraZeneca, Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA, UK., Cheong PH; Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR, 97331, USA., Smith AD; EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2020 May 11; Vol. 59 (20), pp. 7897-7905. Date of Electronic Publication: 2020 Mar 11.
DOI: 10.1002/anie.201916480
Abstrakt: Axially chiral phenols are attractive targets in organic synthesis. This motif is central to many natural products and widely used as precursors to, or directly, as chiral ligands and catalysts. Despite their utility few simple catalytic methods are available for their synthesis in high enantiopurity. Herein the atropselective acylation of a range of symmetric biaryl diols is investigated using isothiourea catalysis. Studies on a model biaryl diol substrate shows that the high product er observed in the process is a result of two successive enantioselective reactions consisting of an initial enantioselective desymmetrization coupled with a second chiroablative kinetic resolution. Extension of this process to a range of substrates, including a challenging tetraorthosubstituted biaryl diol, led to highly enantioenriched products (14 examples, up to 98:2 er), with either HyperBTM or BTM identified as the optimal catalyst depending upon the substitution pattern within the substrate. Computation has been used to understand the factors that lead to high enantiocontrol in this process, with maintenance of planarity to maximize a 1,5-S⋅⋅⋅O interaction within the key acyl ammonium intermediate identified as the major feature that determines atropselective acylation and thus product enantioselectivity.
(© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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