Development of New Gold(Ⅰ)-Catalyzed Reactions of 3-Alkoxy-1,n-enynes and 4-(Alkoxyalkyl)oxy-1-butynes

DoctorThe addition reaction to a carbon-carbon multiple bond in a catalytic version is one of the most important processes for organic synthesis, because this process can establish new chemical bonds in an efficient and atom-economic manner. Various transition metal-catalyzed addition reactions of pronucleophiles such as H-CR3, H-NR2, H-OR, H-OC(O)R, H-SR have been developed and become a powerful strategy to establish a variety of carbon-carbon and carbon-heteroatom bonds. However, addition reaction of a carbon-oxygen bond to carbon-carbon multiple bond in a catalytic manner, so-called carboalkoxylation, has rarely been investigated. It may result from the lower reactivity of a carbon-oxygen bond in ethers,7 although this process is powerful strategy to establish both carbon-carbon and carbon-oxygen bonds simultaneouslyBy the end of 2005, the studies on catalytic carboalkoxylation had been limited to the substrates bearing allyl or propargyl ethers and benzaldehyde acetals by palladium catalyst, and also those generable quite stable cationic alkyl groups such as allyl / benzyl / α-alkoxyalkyl ethers by platinum(Ⅱ) catalyst. In recent years, gold(I)-catalyzed reactions allowed methyl ethers and propargyl esters bearing benzyl tether to be applied as a substrate of the carboalkoxylation through distinct pathway from palladium and platinum(Ⅱ)-catalyzed carboalkoxylation.Gold(I)-catalyzed reaction using unique reactivity of cationic gold(I) complex, both soft and strong Lewis acid, makes nucleophilic addition into activated alkyne very facile.Gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes would open promising avenue for highly efficient formation of synthetically useful mono- and bicyclic cycloheptene frameworks through conceptually new mode featuring tandem heterocyclization and novel [3,3]-sigmatropic rearrangement beyond transition metal-catalyzed carboalkoxylation which mostly provides cyclopentadiene or furan frameworks as products. Furthermore, the cycloisomerization easily proceeds under very mild conditions with affording the cycloisomerized products in almost quantitative yields. The synthetic utility of this cycloisomerization is demonstrated by facile conversion to various cyclohept-4-en-1-ones.Gold(I)-catalyzed cycloisomerization of 3-methoxy-1,7-enynes largely depends on structure of substrate unlike that of 3-methoxy-1,6-enynes. This cycloisomerization selectively provides either cyclooctene frameworks by [3,3]-sigmatropic rearrangement as key event or cyclohaxane frameworks by carboalkoxylation. It can be easily operated under very mild conditions in high yields.Gold(I)-catalyzed cycloisomerization of 4-(alkoxyalkyl)oxy-1-butynes provides a new access to highly substituted tetrahydropyran-4-ones in an efficient and atom-economic manner. Of particular noteworthy is the unique phosphine ligand effect on the stereoselectivity in the formation of tetrahydropyranone as product