Supported Gold Nanoparticles for Efficient α‐Oxygenation of Secondary and Tertiary Amines into Amides

Abstract

Although the α‐oxygenation of amines is a highly attractive method for the synthesis of amides, efficient catalysts suited to a wide range of secondary and tertiary alkyl amines using O2 as the terminal oxidant have no precedent. This report describes a novel, green α‐oxygenation of a wide range of linear and cyclic secondary and tertiary amines mediated by gold nanoparticles supported on alumina (Au/Al2O3). The observed catalysis was truly heterogeneous, and the catalyst could be reused. The present α‐oxygenation utilizes O2 as the terminal oxidant and water as the oxygen atom source of amides. The method generates water as the only theoretical by‐product, which highlights the environmentally benign nature of the present reaction. Additionally, the present α‐oxygenation provides a convenient method for the synthesis of 18O‐labeled amides using H218O as the oxygen source.

Alternative Approach to the Large-Scale Synthesis of the Densely Functionalized Pyrrolidone BMT-415200

“…Di-tert-butyl (2S,3S,4R)-3-Ethyl-4-hydroxypyrrolidine-1,2dicarboxylate (8). 1 Di-tert-butyl (2S,3S,4S)-3-Ethyl-4-hydroxypyrrolidine-1,2dicarboxylate (15). 1 (9).…”

“… , We proposed nucleophilic deoxyfluorination on the secondary alcohol − of 8 to establish the S -stereocenter bearing the fluoro substituent to afford pyrrolidine 9 . We sought to leverage a C–H oxidation reaction − on pyrrolidine 9 to install the 2-oxo center to furnish pyrrolidone 10 . Boc deprotection, transesterification, and chemoselective reduction of the ester functionality − would provide alcohol 2 , which upon mesylation − would lead to the desired mesylate 1 .…”

Facile Preparation of 4-(4-Nitrophenyl)morpholin-3-one via the Acid-Catalyzed Selective Oxidation of 4-(4-Nitrophenyl)morpholine by Sodium Chlorite as the Sole Oxidant

“…Ferric chloride-catalyzed oxidation cyclic amines offered a lower-cost process for obtaining lactams (Scheme , eq 3), but the substrate scope is currently limited due to the use of a strong peroxide oxidant . The heterogeneous gold nanoparticle supported on alumina is a mild and chemoselective route for amide and lactam formation (Scheme , eq 4); however, the catalyst loading is too large, the gold catalyst is costly, and the catalyst preparation is tedious. From an environmental perspective, the transient metal-free process is promising.…”

Transition-Metal-Free Amine Oxidation: A Chemoselective Strategy for the Late-Stage Formation of Lactams

“…However, large amounts of this expensive catalyst are required, which is further complicated by the multistep process to prepare the colloid. 10 In contrast to the use of transition-metal catalysts, molecular iodine is a mild, cheap, and metal-free oxidant 11 that has been used to chemoselectively oxidize a piperidine ring found in natural products to the corresponding lactam in the presence of aldehyde, alkene, alcohol, and heteroaromatic functionalities. 12 Although there are a number of reports that describe the use of electrophilic halogen sources to carry out α-oxidation of cyclic amines, 13 these procedures to date have limited functional group tolerance 13a and require harsh reaction conditions.…”

“…Gold nanoparticles supported on alumina do offer a mild and chemoselective route to amide and lactam formation. However, large amounts of this expensive catalyst are required, which is further complicated by the multistep process to prepare the colloid . In contrast to the use of transition-metal catalysts, molecular iodine is a mild, cheap, and metal-free oxidant that has been used to chemoselectively oxidize a piperidine ring found in natural products to the corresponding lactam in the presence of aldehyde, alkene, alcohol, and heteroaromatic functionalities .…”