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The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon-carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries1. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism2. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.
Classified by their mechanistic profile, metathesis reactions most often proceed through a [2+2] cycloaddition to form a 4-atom cyclic intermediate, followed by [2+2] cycloreversion, resulting in an exchange of reactive partners3-6. Included in this mode of reactivity are classical olefination reactions (Fig. 1a), in which highly polarized nucleophilic components add to carbonyl derivatives to give cyclic intermediates7-9. These compounds then fragment to produce olefins and a metal or main-group oxo species, the latter being the thermodynamic driving force for the reaction. The utility of this chemistry is often hampered by harsh conditions, the need for pre-functionalized intermediates and the production of excess quantities of waste products. A revolutionary development in this regard was the establishment of the catalytic olefin-olefin metathesis reaction, in which transition- metal alkylidenes facilitate [2+2] cycloadditions and subsequent [2+2] cycloreversions from simple olefin starting materials (Fig. 1b). Since its discovery, olefin metathesis has led to marked advances in the fields of organic chemistry as well as chemical biology, and allowed entry into previously inaccessible complex molecules. Although it was discovered at around the same time, the corresponding carbonyl-olefin metathesis (Fig. 1c) is much less developed10. To...