Copper-Catalyzed Modular Amino Oxygenation of Alkenes: Access to Diverse 1,2-Amino Oxygen-Containing Skeletons

Abstract

Copper-catalyzed alkene amino oxygenation reactions using O-acylhydroxylamines have been achieved for a rapid and modular access to diverse 1,2-amino oxygen-containing molecules. This transformation is applicable to the use of alcohols, carbonyls, oximes and thio-carboxylic acids as nucleophiles on both terminal and internal alkenes. Mild reaction conditions tolerate a wide range of functional groups, including ether, ester, amide, carbamate, and halide. The reaction protocol allows for starting with free amines as the precursor of O-benzoylhydroxylamines to eliminate their isolation and purification, contributing to broader synthetic utilities. Mechanistic investigations reveal the amino oxygenation reactions may involve distinct pathways, depending on different oxygen nucleophiles.

Radical‐Mediated Approaches for the Synthesis of Thiolactones

“…In 2019 Wang and co‐workers reported a copper‐catalyzed modular amino oxygenation of alkenes which gives access to diverse 1,2‐amino oxygen‐containing skeletons [44] . Within this body of work, it was shown that the methodology could be extended towards the synthesis of a γ‐thiolactone (Scheme 13).…”

Triethyl Phosphite/Benzoyl Peroxide Mediated Reductive Dealkylation of O‐Benzoylhydroxylamines: A Cascade Synthesis of Secondary Amides

“…Encouraged by this result, O ‐BHA 1 and BPO 2 were chosen as representative reactants for further optimization of the reaction. In the presence of triethyl phosphite in DCE at 60 °C, reductively dealkylated 2° amide 3 was indeed obtained in 62 % yield, along with benzaldehyde (44 %) and benzoic acid (90 %) as side products (Table , entry 1).…”

Copper-Catalyzed 1,2-Amino Oxygenation of 1,3-Dienes: A Chemo-, Regio-, and Site-Selective Three-Component Reaction with O-Acylhydroxylamines and Carboxylic Acids

“…In this work, we have developed a copper-catalyzed three-component 1,2-amino oxygenation reaction of 1,3-dienes, using O -acyl hydroxylamines as the electrophilic nitrogen source and carboxylic acids as the nucleophilic oxygen source (Scheme 1C). The transformation is envisioned to be initiated by a copper-catalyzed amination of dienes with electrophilic O -acyl hydroxylamines 10 followed by the nucleophilic addition of carboxylic acids. Such amination/oxygenation pathways are distinctly different from previous 1,3-diene methods and thus would allow for a chemo-, regio- and site-selective addition to 1,3-dienes.…”

“…Interestingly, these amino oxygenation conditions show remarkable selectivity toward 1,3-dienes over non-conjugated olefins, which are also known to undergo similar amino oxygenation reactions. 10 This method also tolerates a diverse scope of carboxylic acids, even those that contain sensitive functional groups. Studies on the reaction pathways offer further mechanistic insights on the radical intermediates and pathways under reaction conditions.…”

“…Our previous studies on copper-catalyzed amino oxygenation of alkenes using O -benzoyhydroxylamines have suggested the presence of radical pathways under similar reaction conditions. 10 To probe the involvement of any possible radical intermediates in the reaction of dienes, the reaction of diene 2a was performed in the presence of radical scavengers (Scheme 4). With the presence of one equivalent of butylated hydroxytoluene (BHT) as a radical scavenger in the reaction of 2a , the desired product 4c was obtained in a decreased 30% yield, along with the formation of two BHT-derived products, 11 and 12 .…”