Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Lactams: Enantioselective Construction of All-Carbon Quaternary Stereocenters in Saturated Nitrogen-Containing Heterocycles

• Published in: Organic letters Vol. 25; no. 35; pp. 6479 - 6484
• Main Authors: Zhang, Tianyi, Nishiura, Yuji, Cusumano, Alexander Q., Stoltz, Brian M.
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 08.09.2023; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Letter; Physical Sciences; Science & Technology; BETA,BETA-DISUBSTITUTED ENONES; KETONES; LIGANDS; MECHANISM; 1,3-DICARBONYL COMPOUNDS; SCAFFOLDS; MICHAEL ADDITIONS; CENTERS; ALKALOIDS
• ISSN: 1523-7060; 1523-7052; 1523-7052
• DOI: 10.1021/acs.orglett.3c02064

Stereogenic nitrogen-containing heterocycles are ubiquitous in natural products and pharmaceutical compounds, but methods for their enantioselective construction have remained elusive. We report a general method for the asymmetric conjugate addition of arylboronic acids to β-alkyl/aryl α,β-unsaturated lactams that affords chiral β,β-disubstituted lactams. The transformation is operationally simple and air- and moisture-tolerant and uses a commercially available (S)-t-Bu-PyOx ligand. The method is high-yielding (up to 95% yield) and enantioselective (up to 97% ee) for a wide range of arylboronic acids and α,β-unsaturated lactams, including those with different ring sizes.