Isothiourea‐catalyzed acylative kinetic resolution of tertiary α‐Hydroxy esters
| Autor: | Samuel M. Smith, Víctor Laina-Martín, Andrew D. Smith, Mark D. Greenhalgh, Rifahath M. Neyyappadath, Shen Qu |
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| Přispěvatelé: | European Commission, The Royal Society, University of St Andrews. School of Chemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Steric effects
Substituent tertiary alcohols Enantioselectivity 010402 general chemistry Medicinal chemistry 01 natural sciences Catalysis Stereocenter Kinetic resolution Acylation chemistry.chemical_compound enantioselectivity QD kinetic resolution acyl transfer Acyl transfer Research Articles Chemistry Organocatalysis 010405 organic chemistry Tertiary alcohol Enantioselective synthesis DAS General Chemistry General Medicine QD Chemistry 0104 chemical sciences Selectivity Research Article |
| Zdroj: | Angewandte Chemie (International Ed. in English) |
| ISSN: | 1433-7851 |
| Popis: | A highly enantioselective isothiourea‐catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently‐developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous‐flow process using a polymer‐supported variant of the catalyst. Lewis base catalyzed kinetic resolution of acyclic tertiary alcohols was achieved with selectivity factors of up to 200. Enantiodiscrimination is proposed to be reliant on the alcohol substrate containing a carbonyl recognition motif. The method, which tolerates aryl, heteroaryl, vinyl, and alkyl substituents, was also translated to continuous flow using a solid‐supported variant of the catalyst. |
| Databáze: | OpenAIRE |
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