Getting excited about cycloadditions Schmidt, Valerie A
Science (American Association for the Advancement of Science),
03/2021, Volume:
371, Issue:
6536
Journal Article
Cycloadditions, such as the 4+2 Diels-Alder reaction to form six-membered rings, are among the most powerful and widely used methods in synthetic chemistry. The analogous 2+2 alkene cycloaddition to ...synthesize cyclobutanes is kinetically accessible by photochemical methods, but the substrate scope and functional group tolerance are limited. Here, we report iron-catalyzed intermolecular 2+2 cycloaddition of unactivated alkenes and cross cycloaddition of alkenes and dienes as regio- and stereoselective routes to cyclobutanes. Through rational ligand design, development of this base metal–catalyzed method expands the chemical space accessible from abundant hydrocarbon feedstocks.
One dioxygenation please, hold the metal: In the presence of either oxygen or air as the sole oxidant and external oxygen atom source, a variety of unsaturated hydroxamic acids afford cyclic ...hydroxamates that are readily converted into 1,2‐diols, with the potential for high levels of reaction stereocontrol.
A radical-mediated approach to metal-free alkene oxyamination is described. This method capitalizes on the unique reactivity of the amidoxyl radical in alkene additions to furnish a general ...difunctionalization using simple diisopropyl azodicarboxylate (DIAD) as a radical trap. This protocol capitalizes on the intramolecular nature of the process, providing single regioisomers in all cases. Difunctionalizations of cyclic alkenes provide trans oxyamination products inaccessible using current methods with high levels of stereoselectivity, complementing cis-selective oxyamination processes.
2 + 2 Photocycloadditions are idealized, convergent construction approaches of 4-membered heterocyclic rings, including azetidines. However, methods of direct excitation are limited by the ...unfavorable photophysical properties of imines and electronically unbiased alkenes. Here, we report copper-catalyzed photocycloadditions of non-conjugated imines and alkenes to produce a variety of substituted azetidines. Design principles allow this base metal-catalyzed method to achieve 2 + 2 imine-olefin photocycloaddition via selective alkene activation through a coordination-MLCT pathway supported by combined experimental and computational mechanistic studies.
The selective, intermolecular 1,4-hydrovinylation of conjugated dienes with unactivated α-olefins catalyzed by α-diimine iron complexes is described. Value-added "skipped" diene products were ...obtained with exclusive 1,4-selectivity, and the formation of branched, ( Z)-olefin products was observed with no evidence for alkene isomerization. Mechanistic studies conducted with the well-defined, single-component iron precatalyst (
DI)Fe(COD) (
DI = 2,4,6-Me
-C
H
-N═CMe
); COD = 1,5-cyclooctadiene) provided insights into the origin of the high selectivity. An iron diene complex was identified as the catalyst resting state, and one such isoprene complex, (
DI)Fe(η
-C
H
), was isolated and characterized. A combination of single crystal X-ray diffraction, Mößbauer spectroscopy, magnetic measurements, and DFT calculations established that the complex is best described as a high-spin Fe(I) center ( S
= 3/2) engaged in antiferromagnetic coupling to an α-diimine radical anion ( S
= -1/2), giving rise to the observed S = 1 ground state. Deuterium-labeling experiments and kinetic analyses of the catalytic reaction provided support for a pathway involving oxidative cyclization of an alkene with the diene complex to generate an iron metallacycle. The observed selectivity can be understood in terms of competing steric interactions in the transition states for oxidative cyclization and subsequent β-hydrogen elimination.
Aryl-substituted bis(imino)pyridine cobalt dinitrogen compounds, ((R)PDI)CoN2, are effective precatalysts for the intramolecular 2π + 2π cycloaddition of α,ω-dienes to yield the corresponding ...bicyclo3.2.0heptane derivatives. The reactions proceed under mild thermal conditions with unactivated alkenes, tolerating both amine and ether functional groups. The overall second order rate law for the reaction, first order with respect to both the cobalt precatalyst and the substrate, in combination with electron paramagnetic resonance (EPR) spectroscopic studies established the catalyst resting state as dependent on the identity of the precatalyst and diene substrate. Planar S = ½ κ(3)-bis(imino)pyridine cobalt alkene and tetrahedral κ(2)-bis(imino)pyridine cobalt diene complexes were observed by EPR spectroscopy and in the latter case structurally characterized. The hemilabile chelate facilitates conversion of a principally ligand-based singly occupied molecular orbital (SOMO) in the cobalt dinitrogen and alkene compounds to a metal-based SOMO in the diene intermediates, promoting C-C bond-forming oxidative cyclization. Structure-activity relationships on bis(imino)pyridine substitution were also established with 2,4,6-tricyclopentyl-substituted aryl groups, resulting in optimized catalytic 2π + 2π cycloaddition. The cyclopentyl groups provide a sufficiently open metal coordination sphere that encourages substrate coordination while remaining large enough to promote a challenging, turnover-limiting C(sp(3))-C(sp(3)) reductive elimination.
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