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 industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. 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.

Jacob R. Ludwig received his BSc in chemistry in 2014 from Michigan State University, where he performed research in the laboratory of Jetze Tepe. After graduation, he joined the Schindler lab at the University of Michigan to pursue his PhD degree. Corinna S. Schindler received her diploma in chemistry from the Technical University of Munich. After a research stay with K.C. Nicolaou at the Scripps Research Institute, she joined the group of Erick Carreira at ETH Zü rich for her graduate studies. She then returned to the US to conduct postdoctoral studies with Eric Jacobsen at Harvard before starting her independent career at the University of Michigan in 2013.

Iron(III)-catalyzed carbonyl-olefin ring-closing metathesis represents a new approach toward the assembly of molecules traditionally generated by olefin-olefin metathesis or olefination. Herein, we report detailed synthetic, spectroscopic, kinetic, and computational studies in order to determine the mechanistic features imparted by iron(III), substrate, and temperature to the catalytic cycle. These data are consistent with an iron(III)-mediated asynchronous, concerted [2+2]-cycloaddition to form an intermediate oxetane as the turnover limiting step. Fragmentation of the oxetane via Lewis acid-activation results in the formation of 5- and 6-membered unsaturated carbocycles.

Some of the simplest and most powerful carbon-carbon bond forming strategies take advantage of readily accessible ubiquitous motifs: carbonyls and olefins. Here we report a fundamentally distinct mode of reactivity between carbonyls and olefins that differs from established acid-catalyzed carbonyl-ene, Prins, and carbonyl-olefin metathesis reaction paths. A range of epsilon, zeta-unsaturated ketones undergo Brønsted acid–catalyzed intramolecular cyclization to provide tetrahydrofluorene products via the formation of two new carbon-carbon bonds. Theoretical calculations and accompanying mechanistic studies suggest that this carbocyclization reaction proceeds through the intermediacy of a transient oxetane formed by oxygen atom transfer. The complex polycyclic frameworks in this product class appear as common substructures in organic materials, bioactive natural products, and recently developed pharmaceuticals.

Cobalt­(II) halides in combination with phenoxyimine (FI) ligands generated efficient precatalysts in situ for the C­(sp2)–C­(sp3) Suzuki–Miyaura cross-coupling between alkyl bromides and neopentylglycol (hetero)­arylboronic esters. The protocol enabled efficient C–C bond formation with a host of nucleophiles and electrophiles (36 examples, 34–95%) with precatalyst loadings of 5 mol %. Studies with alkyl halide electrophiles that function as radical clocks support the intermediacy of alkyl radicals during the course of the catalytic reaction. The improved performance of the FI–cobalt catalyst was correlated with decreased lifetimes of cage-escaped radicals as compared to those of diamine-type ligands. Studies of the phenoxyimine–cobalt coordination chemistry validate the L,X interaction leading to the discovery of an optimal, well-defined, air-stable mono-FI–cobalt­(II) precatalyst structure.