1114-59-6Relevant academic research and scientific papers
Mechanistic Insights into Fe Catalyzed α-C?H Oxidations of Tertiary Amines
Legacy, Christopher J.,Hope, Taylor O.,Gagné, Yohann,Greenaway, Frederick T.,Frenette, Mathieu,Emmert, Marion H.
, p. 235 - 246 (2020/10/19)
We report detailed mechanistic investigations of an iron-based catalyst system, which allows the α-C?H oxidation of a wide variety of amines. In contrast to other catalysts that effect α-C?H oxidations of tertiary amines, the system under investigation exclusively employs peroxy esters as oxidants. More common oxidants (e. g. tBuOOH) previously reported to affect amine oxidations via free radical pathways do not provide amine α-C?H oxidation products in combination with the described catalyst system. The investigations described herein employ initial rate kinetics, kinetic profiling, DFT calculations as well as Eyring, kinetic isotope effect, Hammett, ligand coordination, and EPR studies to shed light on the Fe catalyst system. The obtained data suggest that the catalytic mechanism proceeds through C?H abstraction at a coordinated substrate molecule. This rate-determining step occurs either through an Fe(IV) oxo pathway or a 2-electron pathway at an Fe(II) intermediate with bound oxidant. DFT calculations indicate that the Fe(IV) oxo mechanism will be the preferred route of these two possibilities. We further show via kinetic profiling and EPR studies that catalyst activation follows a radical pathway, which is initiated by hydrolysis of PhCO3tBu to tBuOOH. Overall, the obtained mechanistic data support a non-classical, Fe catalyzed pathway that requires substrate binding, inducing selectivity for α-C?H functionalization.
Iron-catalyzed Cα-H oxidation of tertiary, aliphatic amines to amides under mild conditions
Legacy, Christopher J.,Wang, Anqi,O'Day, Brian J.,Emmert, Marion H.
supporting information, p. 14907 - 14910 (2016/02/05)
De novo syntheses of amides often generate stoichiometric amounts of waste. Thus, recent progress in the field has focused on precious metal catalyzed, oxidative protocols to generate such functionalities. However, simple tertiary alkyl amines cannot be used as starting materials in these protocols. The research described herein enables the oxidative synthesis of amides from simple, noncyclic tertiary alkyl amines under synthetically useful, mild conditions through a biologically inspired approach: Fe-catalyzed Cα-H functionalization. Mechanistic investigations provide insight into reaction intermediates and allow the development of a mild Cα-H cyanation method using the same catalyst system. The protocol was further applied to oxidize the drug Lidocaine, demonstrating the potential utility of the developed chemistry for metabolite synthesis. Let′s iron it out! The title reaction enables the oxidative synthesis of amides directly from tertiary, noncyclic alkyl amines under synthetically useful, mild conditions through a biologically inspired approach employing oxidative iron catalysis. Mechanistic studies suggest that hemiaminals are likely intermediates in this reaction and that the catalytic system can be employed for other Cα-H oxidations of amines.
Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
supporting information, p. 2955 - 2965 (2013/09/02)
An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
Silicon Hydrides and Molybdenum(O) Catalyst: A Novel Approach for Conjugate Reduction of α,β-Unsaturated Carbonyl Compounds
Keinan, Ehud,Perez, Daniel
, p. 2576 - 2580 (2007/10/02)
A novel reducing system comprised of phenylsilane and catalytic amounts of Mo(CO)6 in refluxing THF efficiently effects conjugate reduction of Michael acceptors, including α,β-unsaturated ketones, carboxylic acids, carboxylic esters, amides, and nitriles.The process involves molybdenum-catalyzed hydrosilation, followed by hydrolysis of the intermediate silyl enol ether.Hydride is regioselectively transferred from the hydridosilane to the β-carbon of the substrate, and a proton from water is incorporated into the α-carbon.
