Macrolactonization Reactions Driven by a Pentafluorobenzoyl Group. (3rd August 2021)

• Record Type: Journal Article
• Authors: Force, Guillaume; Perfetto, Anna; Mayer, Robert J.; Ciofini, Ilaria; Lebœuf, David
• Is Part Of: Angewandte Chemie. Volume 133:Number 36(2021)
• Page Start: 19996
• Page End: 20004
• Publication Date: 2021-08-03
• Subjects: hydroxyacids -- macrocyclization -- macrodiolides -- macrolactones -- mixed anhydride; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202105882
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Macrolactones constitute a privileged class of natural and synthetic products with a broad range of applications in the fine chemicals and pharmaceutical industry. Despite all the progress made towards their synthesis, notably from seco ‐acids, a macrolactonization promoter system that is effective, selective, flexible, readily available, and, insofar as possible, compatible with manifold functional groups is still lacking. Herein, we describe a strategy that relies on the formation of a mixed anhydride incorporating a pentafluorophenyl group which, due to its high electronic activation enables a convenient access to macrolactones, macrodiolides and esters with a broad versatility. Kinetic studies and DFT computations were performed to rationalize the reactivity of the pentafluorophenyl group in macrolactonization reactions. Abstract : Old made new again: The onset of macrolactonizations can be initiated using the inexpensive pentafluorobenzoyl chloride as an activating agent to deliver a large variety of macrolactones, macrodiolides and esters with high efficiency through a robust protocol. Notably, this process could be easily extended to less reactive phenol derivatives.