Investigations into the Mechanism of Inter- and Intramolecular Iron-Catalyzed [2 + 2] Cycloaddition of Alkenes

Abstract

Mechanistic studies are reported on the inter- and intramolecular [2 + 2] alkene cycloadditions to form cyclobutanes promoted by (^tricPDI)Fe(N₂) (^tricPDI = 2,6-(2,4,6-tricyclopentyl)C₆H₂N = CMe)₂C₅H₃N). A combination of kinetic measurements, freeze-quench ⁵⁷Fe Mössbauer and infrared spectroscopic measurements, deuterium labeling studies, natural abundance ¹³C KIE studies, and isolation and characterization of catalytically relevant intermediates were used to gain insight into the mechanism of both inter- and intramolecular [2 + 2] cycloaddition reactions. For the stereo- and regioselective [2 + 2] cycloaddition of 1-octene to form <i>trans</i>-1,2-dihexylcyclobutane, a first-order dependence on both iron complex and alkene was measured as well as an inverse dependence on N₂ pressure. Both ⁵⁷Fe Mössbauer and infrared spectroscopic measurements identified (^tricPDI)Fe(N₂)(η²-1-octene) as the catalyst resting state. Rate-determining association of 1-octene to (^tricPDI)Fe(η²-1-octene) accounts for the first order dependence of alkene and the inverse dependence on N₂. Heavy atom ¹³C/¹²C kinetic isotope effects near unity also support post rate-determining C-C bond formation. By contrast, the intramolecular iron-catalyzed [2 + 2] cycloaddition of 1,7-octadiene yielded <i>cis</i>-bicyclo[4.2.0]octane in 92:8 d.r. and a first order dependence on the iron precursor and zeroth order behavior in both diene and N₂ pressure were measured. A pyridine(diimine) iron <i>trans</i>-bimetallacycle was identified as the catalyst resting state and was isolated and characterized by X-ray diffraction and ¹H NMR and ⁵⁷Fe Mössbauer spectroscopies. Dissolution of the iron <i>trans</i>-bimetallacycle in benzene-<i>d</i>_<i>6</i> produced predominantly the <i>cis</i>-cyclobutane product, establishing interconversion between the <i>trans</i> and <i>cis</i> metallacycles during the catalytic reaction and consistent with a Curtin-Hammett kinetic regime. A primary ¹³C/¹²C kinetic isotope effect of 1.022(4) was measured at 23 °C, consistent with irreversible unimolecular reductive elimination to form the cyclobutane product. Despite complications from competing cyclometalation of chelate aryl substituents, deuterium labeling experiments were consistent with unimolecular C-C reductive elimination that occurred either by a concerted pathway or a radical rebound sequence that is faster than C-C bond rotation.