Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2 + 2] cycloaddition: a synthetic and computational study† †Electronic supplementary information (ESI) available: Experimental procedures, product characterisation data (mpt, NMR, IR, HRMS, [α]D, HPLC), traces (1H, 13C, 19F NMR, HPLC), X-ray crystallographic data (CCDC 1886142, CCDC 1886143 and CCDC 1886144), coordinates, thermal corrections and energies of all computed structures. CCDC 1886142–1886144. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c9sc00390h

Autor: Barrios Antúnez, Diego-Javier, Greenhalgh, Mark D., Brueckner, Alexander C., Walden, Daniel M., Elías-Rodríguez, Pilar, Roberts, Patrick, Young, Benjamin G., West, Thomas H., Slawin, Alexandra M. Z., Ha-Yeon Cheong, Paul, Smith, Andrew D.
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Chemical Science
ISSN: 2041-6539
2041-6520
Popis: A study into the Lewis base-catalysed enantioselective synthesis of polyfluorinated β-lactones.
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 (RF = CF3, C2F5, C4F9) is reported. Following optimisation, high diastereo- and enantioselectivity was observed for β-lactone formation using C2F5- and C4F9-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 CF3-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 13C 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.
Databáze: OpenAIRE
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