Asymmetric Construction of Multifunctional γ-Lactams from 1,3-Dienes and α-Ketoamides via Pd(0)-π-Lewis Base Catalysis
Guo-Li Shen, Yuan-Yuan Tan, Yuan Hu, Zhi-Chao Chen*, Wei Du and Ying-Chun Chen*
*West China School of Pharmacy, Sichuan University, Chengdu,
Sichuan 610041, China, Email: chenzhichao
scu.edu.cn, ycchenscu.edu.cn
G.-L. Shen, Y.-Y. Tan, Y. Hu, Z.-H. Chen, W. Du, Y.-C. Chen, Org. Lett., 2023, 25, 6649-6653.
DOI: 10.1021/acs.orglett.3c02443
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Abstract
An asymmetric palladium-catalyzed vinylogous addition/allylic amination process between 1,3-dienes and α-ketoamides provides multifunctionalized γ-lactams, including those bearing two tetrasubstituted stereogenic centers. This protocol features advantages of ready substrate availability, broad applicability, high efficiency, and excellent stereoselectivity.
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General procedure for asymmetric synthesis of Multifunctional γ-Lactams
To an oven dried 10 mL Schlenk tube equipped with a stirring bar were added α-oxocarboxamide (0.100 mmol, 1.0 equiv), Pd2(dba)3 (2.5 or 5.0 mol %) and ligand (10.0 or 20.0 mol %). The tube was capped, evacuated and back-filled with argon for five times. Then degassed dry toluene (1.0 mL) and 1,3-diene (0.200 mmol, 2.0 equiv) were added via syringe sequentially under atmosphere of argon. The mixture was stirred at 80 °C for 18-120 h. After complete consumption of α-oxocarboxamide (monitored by TLC), the mixture was directly purified by flash chromatography on silica gel (petroleum ether/EtOAc) to afford product.
Key Words
γ-lactams, Pd(0)-π-Lewis base, 1,3-dienes, α-ketoamides
ID: J54-Y2023
