Iridium‐Catalysed Reductive Deoxygenation of Ketones with Formic Acid as Traceless Hydride Donor

Abstract

An iridium-catalysed deoxygenation of ketones and aldehydes is achieved, with formic acid as hydride donor and water as co-solvent. At low catalyst loading, a number of 4-(N,N-disubstituted amino) aryl ketones are readily deoxygenated in excellent yields and chemoselectivity. Numerous functional groups, especially phenolic and alcoholic hydroxyls, secondary amine, carboxylic acid, and alkyl chloride, are well tolerable. Geminally dideuterated alkanes are obtained with up to 90% D incorporation, when DCO 2 D and D 2 O are used in place of their hydrogenative counterparts. The activating 4-(N,N-disubstituted amino)aryl groups have been demonstrated to undergo a variety of useful transformations. The deoxygenative deuterations have been used to prepare a deuterated drug molecule Chlorambucil-4,4-d 2 .

Water-soluble and reusable Ru-NHC catalyst for aqueous-phase transfer hydrogenation of quinolines with formic acid

“…4 In terms of the application domain of homogeneous TH protocols using FA, varieties of organic unsaturated compounds were well-explored during the past decades. 5 In contrast, charging N-heteroarenes (such as quinolines and related N-heterocycles) via H + /H − -transfer using FA is so far underdeveloped with only a handful of reports, and those too are dominated by Rh- 6 and Ir-based organometallic catalysts, 7 with the exception of only one report based on a Co-phosphine catalyst 8 (Fig. 1).…”

Manganese-mediated reductive N,N-dialkylation of nitroarenes: a dramatic NiI2 effect

“…(3) Eventually, by employing PhNO 2 and the cheap 2-iodoethanol 2k as the substrates, intermediate 6 could be prepared in 68% isolated yield under our modified conditions (eqn (3)). Given that 6 has been reported as a key intermediate for the preparation of the drug chlorambucil, 1 our method provides a new option for the synthesis of such drugs. In addition, the successful execution of the above examples further demonstrates the good functional group tolerance of our protocol, as sulfonamide, ether, trifluoromethyl and hydroxyl groups were tolerated in these transformations.…”

“…1). [1][2][3][4] For example, chlorambucil is approved by the FDA to treat cancer, 1 and N 1 ,N 1 -dimethyl-N 4 phenylpiperazinium iodide (DMPP) is a well-known nicotinic agonist. 2 ZM-093 and YL-OD have been reported to be a metalloenzyme inhibitor 3 and a fluorescent probe 4 for detecting azo reductase, respectively.…”

Metal–Organic Framework-Confined Single-Site Base-Metal Catalyst for Chemoselective Hydrodeoxygenation of Carbonyls and Alcohols

“…To improve the atom economy and preclude hazardous reagents, transition-metal-catalyzed deoxygenation has been developed. Catalytic protocols for deoxygenation typically rely on the toxic and precious late transition metals and require a stoichiometric amount of reductants such as silane, − alcohol, formic acid, hydrazine, or hydrogen. − Among all of the reductants, H 2 is the most atom-efficient and nontoxic and also produces H 2 O as the only byproduct. However, the catalytic deoxygenation reaction using H 2 (hydrodeoxygenation) is usually executed at high temperatures and pressures with the explosion risk.…”

“…Hydrodeoxygenation of carbonyls and alcohols catalyzed by late transition metals − ,− ,− and base metals. ,− …”