Syntheses of Substituted α,β-Unsaturated δ-Lactams from N-Boc-2,4-dioxopiperidine

Saiya Liu; Chenchen Zhang; Qihua Xiong; Yuexin Liu; Lu Li; Yongqiang Sun; Bichu Cheng; Fener Chen

doi:10.1021/acs.joc.3c01027

Syntheses of Substituted α,β-Unsaturated δ-Lactams from N-Boc-2,4-dioxopiperidine

J Org Chem. 2023 Dec 15;88(24):17489-17493. doi: 10.1021/acs.joc.3c01027. Epub 2023 Nov 22.

Authors

Saiya Liu¹, Chenchen Zhang¹, Qihua Xiong¹, Yuexin Liu¹, Lu Li¹, Yongqiang Sun¹, Bichu Cheng^{1

2}, Fener Chen^{1

3}

Affiliations

¹ School of Science, Green Pharmaceutical Engineering Research Center, Harbin Institute of Technology, Shenzhen 518055, China.
² State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
³ Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China.

PMID: 37992127
DOI: 10.1021/acs.joc.3c01027

Abstract

A method for the syntheses of substituted α,β-unsaturated δ-lactams (2) from the commercially available compound N-Boc-2,4-dioxopiperidine (1) has been developed. The α-substituents were introduced by a reductive Knoevenagel condensation reaction, and the β-substituents were installed by palladium-catalyzed cross coupling reactions. More than 20 diverse examples were prepared in 2-3 steps. The synthesis was operationally simple, user-friendly, and easy to scale up.