Aerobic Oxidative Cyclization under Pd(II) Catalysis: A Regioselective Approach to Heterocycles
Kai-Tai Yip, Jin-Heng Li, On-Yi Lee and Dan Yang*
*Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong
Kong, P. R. China, Email: yangdanhku.hk
K.-T. Yip, J.-H. Li, O.-Y. Lee, D. Yang, Org. Lett., 2005, 7, 5717-5719.
DOI: 10.1021/ol052529c
Abstract
An efficient and regioselective Yb(OTf)3-promoted palladium-catalyzed oxidative cyclization of γ-heteroalkenyl β-keto amides has been developed. Under simple aerobic condition, various six-, seven-, and eight-membered-ring N- and O-heterocycles were obtained in excellent yield.
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Details
The document discusses a study on the development of an efficient method for synthesizing N- and O-heterocycles through aerobic oxidative cyclization using Pd(II) catalysis. The research, conducted by Kai-Tai Yip, Jin-Heng Li, On-Yi Lee, and Dan Yang from the University of Hong Kong, presents a Yb(OTf)3-promoted palladium-catalyzed process that operates under simple aerobic conditions. This method successfully produces six-, seven-, and eight-membered-ring heterocycles in excellent yields, which are significant structures in many drugs and biologically active compounds.
The study highlights the advantages of using molecular oxygen as a cheap, efficient, and environmentally friendly oxidant over traditional oxidants like CuCl2 or benzoquinone. The optimized conditions involve using PdCl2(MeCN)2 and Yb(OTf)3 in dry THF under 1 atm O2. The method shows high regioselectivity and efficiency, with the formation of various N- and O-heterocycles, including those with different substituents.
The researchers also conducted deuterium-labeling experiments to understand the reaction mechanism, which involves selective β-H elimination and Pd-migration steps. The study concludes that this mild and efficient method complements existing carbocycle formation techniques and opens new possibilities for synthesizing heterocycles. Further investigations are ongoing to expand the scope of this Pd(II)-catalyzed aerobic oxidative cyclization.
Key Words
Cyclization, Cyclic Amines, Cyclic Ethers, Active Methylenes
ID: J54-Y2005-2150