α-Phenylthioaldehydes for the effective generation of acyl azolium and azolium enolate intermediates
Date
14/05/2024Author
Grant ID
EP/L016419/1
EP/S019359
EP/W007517/1
Keywords
Metadata
Show full item recordAbstract
a-Phenylthioaldehydes are readily prepared using a simple multi-step procedure and herein are introduced as a new precursor for the NHC-catalysed generation of acyl azolium and azolium enolate intermediates that are of widespread synthetic interest and utility. Treatment of a-phenylthioaldehydes with an NHC precatalyst and base produces an efficient redox rearrangement via a Breslow intermediate, elimination of thiophenolate, and subsequent rebound addition to the generated acyl azolium to give the corresponding thiol ester. In the presence of an external alcohol, competition between redox rearrangement and redox esterification can be controlled through judicious choice of the N-aryl substituent within the NHC precatalyst and the base used in the reaction. With NEt3 as base, NHCs bearing electron-withdrawing (N-C6F5 or N-C6H2Cl3) substituents favour redox rearrangement, while triazolium precatalysts with electron-rich N-aryl substituents (N-Ph, N-Mes) result in preferential redox esterification. Using DBU, redox esterification is preferred due to transesterification. Additionally, a-phenylthioaldehyde-derived azolium enolates have been used in enantioselective formal [4+2]-cycloaddition reactions to access dihydropyridinone heterocycles with high enantioselectivity (up to >95:5 dr, 98:2 er).
Citation
Ewing , P , Majhi , P , Prentice , C , Young , C M , Van Rees , K , Arnold , P , Zysman-Colman , E & Smith , A D 2024 , ' α-Phenylthioaldehydes for the effective generation of acyl azolium and azolium enolate intermediates ' , Chemical Science , vol. 24 , no. 15 , pp. 9369-9375 . https://doi.org/10.1039/D3SC06879J
Publication
Chemical Science
Status
Peer reviewed
ISSN
2041-6520Type
Journal article
Description
The research leading to these results has received funding from the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) (PE, EP/L016419/1), the University of St Andrews (CP), the EPSRC (CMY, EP/S019359/1) and the EU (Marie-Curie Fellowship to PKM, Advanced Research Grant to PLA, 740311). Part of the work was supported by the U.S. Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division, in the Catalysis Program at the Lawrence Berkeley National Laboratory under contract no. DE-AC02- 05CH11231 (PLA). ADS and EZ-C thank the EPSRC Programme Grant “Boron: Beyond the Reagent” (EP/W007517) for support.Collections
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