Pd-Catalyzed Cyclization Of Allenamides

The allenamides are important precursors and structural units in organic synthesis.At the same time,the study of synthesis and transformation of allenamides are important for the development of medicine and the natural products.Allenamide as a more electron-rich allene,the intramolecularly active allene and amide groups allow allenetoine to exhibit unique reactivity and stability.Allenamide can be catalyzed by a variety of transition metal catalysts to generate more highly active intermediates,and further transformations can be achieved by coupling,addition,oxidation,nucleophilic substitution,cyclization,etc.to achieve C-X bonds construction.The main works of this issue were focused on the cyclization reaction of transition metal palladium catalyzed allenamides,and develops several synthetic methods for the substitution of six-membered nitrogen and oxygen heterocyclic compounds,providing new ideas and new strategies for the efficient construction of natural product skeletons.The detailed research contents mainly include the following two aspects:1)Palladium-Catalyzed Cyclization-Heck Reaction of Allenamides with aryl iodide to construct of 3-methylene-5-phenyl-1,2,3,4-tetrahydropyridine derivatives.Synthesis of N-Ts/Ms/Boc stable allenamides and capture by aryl iodide intermediates,coupling cyclization to give 3-methylene-5-phenyl-1,2,3,4tetrahydropyridine derivatives have achieved a tandem Heck-selective cyclization strategy between allenamides and aryl iodide molecules,the alkenyl bromide also shows better adaptability under this strategy.Through this strategy,we can achieve a one-pot method to efficiently construct two C-C bonds,and selectively perform the allenamides alpha position C participation in the cyclization.The reaction has the characteristics of raw materials,simple catalysts,and mild reaction conditions.2)Palladium-Catalyzed Regioselective Intermolecular [4+2] Cycloaddition of(Z)-3-Iodo-Allylic Nucleophiles and Allenamides.Based on the study of allenamides Heck reaction,we have developed a palladium-catalyzed [4+2] cycloaddition reaction strategy between allenamide and alkenyl iodide nucleophiles.By this method,a series of alkenyl iodides can be efficiently converted into 2-amino-dihydropyran and 2-amino-tetrahydropyridine derivatives,and such molecular skeleton structures are widely present in natural products and active drugs.Most of the products can be obtained with high chem-and regioselectivity and high yield.The difference from system 1 is that the [4+2]cycloaddition reaction achieves the selective cyclization of the allenamine γ-position C.Experiments have shown that the coordination effect of intramolecular substituents has a great influence on the yield.In addition,the RCM reaction was successfully achieved under the catalysis of the Grubbs-II catalyst.For the first time,a series of hexa-penta-spirocyclic compounds were reported.