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Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2 + 2] cycloaddition: a synthetic and computational study
The enantioselective preparation of a range of perfluoroalkyl-substituted β-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (R(F) = CF(3), C(2)F(5), C(4)F(9)) is reported. Following optimisation, high d...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585878/ https://www.ncbi.nlm.nih.gov/pubmed/31360423 http://dx.doi.org/10.1039/c9sc00390h |
Sumario: | The enantioselective preparation of a range of perfluoroalkyl-substituted β-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (R(F) = CF(3), C(2)F(5), C(4)F(9)) is reported. Following optimisation, high diastereo- and enantioselectivity was observed for β-lactone formation using C(2)F(5)- and C(4)F(9)-substituted ketones at room temperature (26 examples, up to >95 : 5 dr and >99 : 1 er), whilst –78 °C was necessary for optimal dr and er with CF(3)-substituted ketones (11 examples, up to >95 : 5 dr and >99 : 1 er). Derivatisation of the β-lactones through ring-opening, as well as a two-step conversion to give perfluoroalkyl-substituted oxetanes, is demonstrated without loss of stereochemical integrity. Density functional theory computations, alongside (13)C natural abundance KIE studies, have been used to probe the reaction mechanism with a concerted asynchronous [2 + 2]-cycloaddition pathway favoured over a stepwise aldol–lactonisation process. |
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