Regioselective Synthesis Of Phenoxy Alkenyl Ethers And Enynyl-Aryl Ethers By Tuning Pd And Cu Catalysts

Phenoxy alkenyl ethers and enynyl-aryl ether derivatives have been considered as the versatile and widely used synthetic intermediates in organic and medicinal chemistry.Numerous applications of these attractive scaffolds have been established for the preparation of natural product analogues,functional materials and pharmaceutically active compounds.Due to lack of atom and step economy using current methods,thus it is a topic of crucial importance to explore more economic and efficient approaches to constructing these bioactive scaffolds.Therefore,in this paper,from the perspective of green chemistry,we based on the C–H functionalization and tandem catalysis strategies and employed transition metal palladium and copper as catalysts,successfully realized the regioselective construction sp² C-O bonds of phenols to synthesize phenoxy alkenyl ethers and enynyl-aryl ethers through reasonable experimental design.Simultaneously,the reaction mechanism was explored in detail.And the main research results of this dissertation are listed as follows:（1）A Pd（Ⅱ）-catalyzed intermolecular approach to sp² C-O bond formation of O-alkenyl phenols with high regio-and stereo-selectivity（only E-isomers）was illustrated.And this procedure efficiently provided 32 aryl alkenyl ether compounds containing the modified of endofolliculina with good isolated yields（up to 84%isolated yield）.The distinctive features of this transformation are the mild conditions（40°C）and using more cost-effective and environment friendly O₂ as the sole oxidant.Finally,the mechanistic study showed that this transformation was not involved in free radicals and was quite different from the common phenoxy radical reaction types.What’s more,the role of excess TBAB（3 equiv）in the reaction system was to avoid the deactivation of the Pd^Ⅱ catalyst arising from the strong coordination by phenol,and therefore promoting the catalytic cycle.（2）A copper/iodide-catalyzed tandem approach to stable enynyl-aryl ether compounds with high regio-and stereo-selectivity（Z-isomers major,and the Z:E ratios were around 84:16）in moderate to excellent isolated yields（up to 88%isolated yield）,using commercially available and cheap phenols and phenylacetylenes without extra ligands,was discovered.And this procedure efficiently provided 38 enynyl-aryl ether derivatives including endofolliculina and indole and can be assembled on the benchtop.Notably,the structure of 8wa was confirmed by X-ray crystallography.And the distinctive feature of our transformation is employing the copper/iodide tandem catalytic system.It not only enriched the content of tandem catalytic reaction to some extent（this distinctive copper/iodide tandem catalysis,a strategy wherein both catalytic cycles can lead to the desired product,obviously differed from the common tandem catalysis,especially the orthogonal tandem catalysis which yielded the target product only in the final catalytic cycle）,but also realized the“cross-electrophile coupling”of C（sp²）-I/C（sp）-I iodine intermediates in iodide catalysis without transition metal and reductant.Similarly,this transformation was also radical-free.