Davies Alyn T, Curto John M, Bagley Scott W, Willis Michael C
Department of Chemistry , University of Oxford , Chemical Research Laboratory , Mansfield Road , Oxford , OX1 3TA , UK . Email:
CVMET Medicinal Chemistry , Pfizer Inc. , Eastern Point Road , Groton , Connecticut 06340 , USA . Email:
Chem Sci. 2017 Feb 1;8(2):1233-1237. doi: 10.1039/c6sc03924c. Epub 2016 Oct 11.
A mild, efficient synthesis of sulfonyl fluorides from aryl and heteroaryl bromides utilizing palladium catalysis is described. The process involves the initial palladium-catalyzed sulfonylation of aryl bromides using DABSO as an SO source, followed by treatment of the resultant sulfinate with the electrophilic fluorine source NFSI. This sequence represents the first general method for the sulfonylation of aryl bromides, and offers a practical, one-pot alternative to previously described syntheses of sulfonyl fluorides, allowing rapid access to these biologically important molecules. Excellent functional group tolerance is demonstrated, with the transformation successfully achieved on a number of active pharmaceutical ingredients, and their precursors. The preparation of peptide-derived sulfonyl fluorides is also demonstrated.
描述了一种利用钯催化从芳基和杂芳基溴化物温和、高效地合成磺酰氟的方法。该过程包括首先使用DABSO作为硫源对芳基溴化物进行钯催化的磺酰化反应，然后用亲电氟源NFSI处理所得的亚磺酸盐。该序列代表了芳基溴化物磺酰化的第一种通用方法，并为先前描述的磺酰氟合成提供了一种实用的一锅法替代方案，能够快速获得这些具有生物学重要性的分子。该方法展示了出色的官能团耐受性，在多种活性药物成分及其前体上成功实现了转化。还展示了肽衍生的磺酰氟的制备。
