Regio- and Diastereoselective Iron-Catalyzed [4+4]-Cycloaddition of 1,3-Dienes

A family of single-component iron precatalysts for the [4+4]-cyclodimerization and intermolecular cross[4+4]-cycloaddition of monosubstituted 1,3-dienes is described. Cyclooctadiene products were obtained with high regioselectivity, and catalyst-controlled access to either cis- or trans-diastereomers was achieved using 4-substituted diene substrates. Reactions conducted either with single-component precatalysts or with iron dihalide complexes activated in situ proved compatible with common organic functional groups and were applied on multigram scale (up to >100 g). Catalytically relevant, S = 1 iron complexes bearing 2-(imino)pyridine ligands, ((PI)-P-R)FeL2 ((PI)-P-R = [2-(2,6-R,-C6H3-N=CMe)-C5H4N] where R = Pr-i or Me, L-2 = bis-olefin), were characterized by single-crystal X-ray diffraction, Massbauer spectroscopy, magnetic measurements, and DFT calculations. The structural and spectroscopic parameters are consistent with an electronic structure description comprised of a high spin iron(I) center (S-Fe = 3/2) engaged in antiferromagnetically coupling with a ligand radical anion (S-PI = -1/2). Mechanistic studies conducted with these single-component precatalysts, including kinetic analyses, C-12/C-13 isotope effect measurements, and in situ Mossbauer spectroscopy, support a mechanism involving oxidative cyclization of two dienes that determines regioand diastereoselectivity. Topographic steric maps derived from crystallographic data provided insights into the basis for the catalyst control through stereoselective oxidative cyclization and subsequent, stereospecific allyl-isomerization and C-C bond forming reductive elimination.