Selective Csp3–F Bond Functionalization with Lithium Iodide

Abstract

A highly efficient method for C–F bond functionalization of a broad variety of activated and unactivated aliphatic substrates with inexpensive lithium iodide is presented. Primary, secondary, tertiary, benzylic, propargylic and α-functionalized alkyl fluorides react in chlorinated or aromatic solvents at room temperature or upon heating to give the corresponding iodides, which are isolated in 91–99% yield. The reaction is selective for aliphatic monofluorides and can be coupled with in situ nucleophilic iodide replacements to install carbon–carbon, carbon–nitrogen, and carbon–sulfur bonds with high yields. Alkyl difluorides, trifluorides, even in activated benzylic positions, are inert under the same conditions and aryl fluoride bonds are also tolerated.

Additive-Free Commercial Alumina Catalyzes the Halogen Exchange Reaction of Long Alkyl Halides in Batch and in Flow Processes

“…Therefore, from a sustainable point of view, the synthesis of alkyl halides from other preformed and widely available organic halides is of interest. In fact, the chemical industry has exerted a great effort in the optimization of this reaction for industrial applications. − This transformation, called halogen exchange (halex) reaction, and shown in Figure , is well-known for metal salts and aromatic halides, where the participation of catalytic or stoichiometric amounts of metals is necessary. − In contrast, the halex reaction of alkyl halides is much less developed and usually requires the use of expensive metal catalysts. − Despite this reaction probably not being used in the chemical industry yet, finding an inexpensive and sustainable catalyst could be of interest to achieve a wider implementation of this reaction.…”

Regioconvergent Nucleophilic Substitutions with Morita–Baylis–Hillman Fluorides

“…Activation of a C sp3 –F bond often requires strong Lewis acids and harsh conditions that may favor competing hydrodefluorination pathways and reduce functional group tolerance, although synthetically attractive protocols for carbon–carbon coupling, − carbon–heteroatom bond formation, − and halide exchange , are known . Our laboratory has contributed to these efforts and introduced several methods that achieve C–F bond functionalization with a variety of alkyl fluorides under mild conditions. − …”