Nickel-Catalyzed Carbonylative Synthesis of Functionalized Alkyl Iodides

摘要

class="head no_bottom_margin" id="sec1title">IntroductionFunctionalized alkyl iodides are potent chemicals in organic chemistry and biology, and many drugs were effectively prepared from alkyl iodides (, , ). Furthermore, ethers are widely used as solvents in organic transformations owing to their high chemical stability and relatively low boiling points. Besides, ethers are also used as strategic protecting groups for hydroxyl functions in organic synthesis (). The cleavage and functionalization of ethers is a versatile reaction in organic synthesis; several methods have been developed for the cleavage of ethers. In addition, many cyclic ethers are derived from biomass, and their ring-opening functionalization is synthetically useful for the synthesis of value-added chemicals (, , , , , , , ). However, owing to the high bond energy of C-O bond, relatively harsh conditions are usually needed for these transformations.On the other hand, transition metal-catalyzed carbonylation reactions, using easily available starting materials to generate synthetically useful carbonyl-containing compounds by incorporating one or more CO into the substrate, have now emerged as one of the most powerful platform in synthetic chemistry (; , ). Typically, nucleophiles such as alcohols, amines, alkynes, and organic metallic compounds were usually used as the reactants for the carbonylative coupling reactions. Studies on carbonylative coupling reactions with weak nucleophiles (i.e., arenes and ethers) have been rarely reported. Recently, Arndtsen and co-workers developed an elegant procedure on carbonylation of arenes for the synthesis of ketones via the in situ formation of aroyl triflate as a highly reactive electrophile (href="#bib8" rid="bib8" class=" bibr popnode">Kinney et al., 2018, href="#bib19" rid="bib19" class=" bibr popnode">Tjutrins and Arndtsen, 2016, href="#bib20" rid="bib20" class=" bibr popnode">Torres et al., 2016, href="#bib17" rid="bib17" class=" bibr popnode">Quesnel and Arndtsen, 2013). However, to the best of our knowledge, the use of ether as the nucleophile in the carbonylation has not been reported because of its low reactivity (href="#bib18" rid="bib18" class=" bibr popnode">Seki et al., 1977, href="#bib22" rid="bib22" class=" bibr popnode">Tsuji et al., 1989, href="#bib23" rid="bib23" class=" bibr popnode">Watanabe et al., 1994, href="#bib6" rid="bib6" class=" bibr popnode">Getzler et al., 2004). Among the catalysts studied, palladium catalysts are more frequently applied. Although nickel catalysts have shown exceptional activities in certain bond activations, their related studies in carbonylation are still rare, which is mainly due to the fear of toxic and volatile Ni(CO)4 formation, and the situation gets even worse with the usage of CO gas. To circumvent the discussed problems, the use of CO surrogates could provide high potential (href="#bib12" rid="bib12" class=" bibr popnode">Morimoto and Kakiuchi, 2004, href="#bib25" rid="bib25" class=" bibr popnode">Wu et al., 2017, href="#bib16" rid="bib16" class=" bibr popnode">Peng et al., 2017). Herein we wish to report our new results on nickel-catalyzed carbonylative cleavage of ethers with Mo(CO)6 as the solid CO source. A broad range of functionalized alkyl iodides can be synthesized from aryl iodides and both cyclic and acyclic ethers. The control experiments showed that the carbonylative cleavage of ether was not proceeding via the intermediate acyl iodide. The ester formation step and the iodine attachment step took place simultaneously and synergistically.