Cascade Oxidative Coupling/Cyclization: A Gateway to 3‑Amino Polysubstituted Five-Membered Heterocycles

• Published in: Journal of organic chemistry Vol. 81; no. 6; pp. 2327 - 2339
• Main Authors: Li, Kaizhi, You, Jingsong
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.03.2016; Amer Chemical Soc
• Subjects: air; amino acids; chemical reactions; Chemistry; Chemistry, Organic; enamines; esters; ketones; moieties; organic chemistry; oxidants; oxygen; Physical Sciences; Science & Technology; C-SP3-H BONDS; ACTIVATION; DIRECT ARYLATION; DIRECT FUNCTIONALIZATION; COUPLING REACTIONS; STRATEGY; TRANSITION-METAL; CARBON-CARBON; IRON; C-H BONDS
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/acs.joc.5b02838

Taking advantage of the coordinating activation strategy, we have developed the cascade oxidative coupling/cyclization of α-C­(sp3)–H bonds of amines with enamines or β-keto esters for the synthesis of three types of five-membered heterocycles. α-Amino acids as the substrate lead to 3-amino 1,3-dihydro-2H-pyrrol-2-ones and furan-2­(3H)-ones by using air or dioxygen as the sole clean oxidant, respectively. α-Amino ketones give a range of 3-amino 1H-pyrroles by using di-tert-butyl peroxide as the oxidant. A three-component, one-pot reaction from readily available amine, β-keto ester, and α-amino ketone enhances the practicality of the modular construction of 1H-pyrrole scaffolds. This programmed protocol features simple reaction conditions, readily available starting materials, broad substrate scope, and high functional group tolerance.