Access to Amino Lactones through Palladium-Catalyzed Oxyamination with Aromatic Amines as the Nitrogen Source

Abstract

Although the synthesis of amino lactones with various nitrogen sources has achieved great success, variants focused on aromatic amine counterparts still remain elusive. Herein, we communicate the intermolecular oxyamination reaction of aromatic amines and unactivated alkenyl carbonyl compounds under palladium catalysis. In the reaction, both primary and second aromatic amines yield the corresponding β-arylamino-γ-lactones efficiently. A key step in this process involves a Pd II /Pd IV catalytic cycle incorporating a 1,2-(C−N)/(C−O) dyotropic rearrangement. This reaction demonstrates mild reaction conditions and good functional group compatibility.

Oxygen-, Nitrogen-, and Sulfur-Containing Heterocycles: Recent Advances in De Novo Synthesis and Prospect

“…Very recently, we have developed a new and convenient palladium-catalyzed intermolecular oxyamination of aromatic amines and unactivated alkenyl carbonyl compounds for constructing β-arylamino-γ-lactones (Scheme ). With a crucial additive KI and essential oxidant TBHP ( tert -butyl hydroperoxide), the reaction works well and affords a broad range of amino lactones in moderate to good yields. Primary and secondary aromatic amines bearing halo, alkyl, alkoxyl, allyl, ester, hydroxyl, and cyano substituents are all tolerated.…”

“…Very recently, we have developed a new and convenient palladium-catalyzed intermolecular oxyamination of aromatic amines and unactivated alkenyl carbonyl compounds for constructing β-arylamino-γ-lactones (Scheme 22). 41 In 2022, we applied an intramolecular chlorine transfer strategy in palladium-catalyzed enantioselective cyclization of 1,6-enynes to access a variety of chiral α-chloromethylene-γbutyrolactones with excellent E selectivity and high enantioselectivity (Scheme 23). 42 Excess halide ions lead to saturated coordination [PdX 4 ] 2− species, which will block the coordination of palladium with chiral ligands, so that high enantioselectivity of enynes by halopalladation progress is undeveloped.…”

Photo‐Induced Oxyamination of Alkenyl Acids towards Amino Lactones

“…[11] Very recently, Jiang developed a Pd-catalyzed oxyamination of 3-butenoic acids and aromatic amines to access β-arylamino-γ-lactones (Scheme 1c). [12] Nevertheless, developing efficient methods for the construction of amino lactones under mild, metal-free and oxidant-free conditions is still highly desired.…”

Editing Tetrasubstituted Carbon: Dual C–O Bond Functionalization of Tertiary Alcohols Enabled by Palladium-Based Dyotropic Rearrangement

“…Type I dyotropic rearrangements are a class of pericyclic valence isomerization reactions in which two σ-bonds simultaneously migrate intramolecularly. , Our group − and others , recently reported a 1,2-aryl­(alkyl)/Pd dyotropic rearrangement and devised several carbofluorination and oxyfluorination reactions by incorporating this elementary step into a Pd II -catalyzed domino process. The C–C bond served as a stationary phase in all these examples. − As a continuation of this research program, we wondered whether this 1,2-positional exchange process could occur along the C–O bond of tertiary alcohols (Scheme a). Owing to the easy access to alkoxy-Pd II complexes, this synthetic transformation would allow dual functionalization of both the hydroxyl group and the tetrasubstituted carbon of tertiary alcohols.…”