Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, iChEM, University of Science and Technology of China, Hefei 230026, China.
Org Lett. 2022 Feb 25;24(7):1471-1475. doi: 10.1021/acs.orglett.1c04359. Epub 2022 Feb 15.
The -difluoroalkene moiety is an ideal carbonyl bioisostere in medicinal chemistry, but efficient synthesis of β--difluoroalkene esters remains challenging so far. Herein, we disclose a photoredox-catalyzed allylic defluorinative alkoxycarbonylation of trifluoromethyl alkenes enabled by intermolecular alkoxycarbonyl radical addition. A wide variety of alcohol oxalate derivatives were amenable, affording various β--difluoroalkene esters with excellent functional group tolerance. Notably, the potential synthetic value of this method is highlighted by successful late-stage modification for bioactive molecules.
-二氟烯基部分是药物化学中理想的羰基生物等排体，但迄今为止，β--二氟烯基酯的有效合成仍然具有挑战性。在此，我们披露了一种通过分子间烷氧基羰基自由基加成实现的三氟乙烯基烯烃的光氧化还原催化烯丙基脱氟烷氧基羰基化反应。各种醇草酸酯衍生物都适用，可得到各种具有优异官能团耐受性的β--二氟烯基酯。值得注意的是，该方法通过对生物活性分子的成功后期修饰，突出了其潜在的合成价值。
