Synthesis of N-Alkenyl 2-Pyridonyl Ethers via a Au(I)-Catalyzed Rearrangement of 2-Propargyloxypyridines.
N-Alkyl 2-pyridones and other enolizable heterocycles are important synthetic constructs, due to their prevalence in natural products and pharmaceutical targets and their capacity to serve as models for a number of biological and chemical processes. The disclosed Au(I)-catalyzed reaction utilizes 2-propargyloxypyridines to access N-alkylated 2-pyridone products derived from both 5-exo and 6-endo addition of the nitrogen to the pendent alkyne. Experimental and computational studies suggest that the desired 5-exo N-alkenyl 2-pyridonyl ethers are formed reversibly in the transformation. After extensive optimization, biaryl Au(I) catalyst 21 was found to overcome the inherent preference for the 6-endo pathway and provide the highest combination of 5-exo selectivity and yield. Herein, we report the application of this new Au(I)-catalyzed C-N bond formation to the preparation of a variety of N-alkenyl 2-pyridonyl ether analogues, which have the potential to serve as an entry point for the synthesis of complex N-alkyl 2-pyridone-containing frameworks.
Department of Chemistry and Biochemistry, Calvin College , 1726 Knollcrest Circle SE, Grand Rapids, Michigan 49546, United States.
Evan O
EO
Romero
Department of Chemistry and Biochemistry, Calvin College , 1726 Knollcrest Circle SE, Grand Rapids, Michigan 49546, United States.
Connor P
CP
Reidy
Department of Chemistry and Biochemistry, Calvin College , 1726 Knollcrest Circle SE, Grand Rapids, Michigan 49546, United States.
Andrea N
AN
Bootsma
Department of Chemistry and Biochemistry, Calvin College , 1726 Knollcrest Circle SE, Grand Rapids, Michigan 49546, United States.
Noah M
NM
PreFontaine
Department of Chemistry and Biochemistry, Calvin College , 1726 Knollcrest Circle SE, Grand Rapids, Michigan 49546, United States.
Nicholas W
NW
Vryhof
Department of Chemistry and Biochemistry, Calvin College , 1726 Knollcrest Circle SE, Grand Rapids, Michigan 49546, United States.
David C
DC
Wierenga
Department of Chemistry and Biochemistry, Calvin College , 1726 Knollcrest Circle SE, Grand Rapids, Michigan 49546, United States.
Carolyn E
CE
Anderson