Ruthenium(II)-catalyzed [2+2] cycloadditions between bicyclic alkenes and alkynes: Scope and limitations

This is an investigation of the scope and limitations of Cp*RuCl(COD) as a [2+2] cycloaddition catalyst. In particular, the ruthenium(II)-catalyzed [2+2] cycloadditions between strained bicyclic alkynes and functionalized alkynes were investigated. The development of this methodology has potential ramifications in natural product synthesis. Moreover, the development of a better understanding surrounding ruthenium(II)catalyzed [2+2] cycloadditions was required for the advancement of this synthetic tool.; Remote substituent studies have provided some valuable information towards the stereoelectronic properties of ruthenium(II)-catalyzed [2+2] cycloadditions between 2-substituted norborn-5-enes and numerous alkynes. We have demonstrated that the cycloaddition proceeds smoothly under favourable conditions (room temperature in most cases) affording only the exo stereoisomers in moderate to high yields (up to 96%). More importantly, low to excellent (up to 15:1) levels of regioselectivity were obtained with various remote substituents. These remote substituent studies have provided a better understanding for the mechanism of a ruthenium(II)-catalyzed [2+2] cycloaddition between an alkene and alkyne.; The reactivity of a wide range of substituted norbornadienes and norbornenes in ruthenium(II)-catalyzed [2+2] cycloadditions were explored. The cycloadditions were found to be highly stereo-, regio-, and chemoselective affording the cycloadducts in moderate to excellent yields (up to 98%). The observed chemoselectivity revealed that the cycloadditions occurred preferentially on the less-substituted double bond. The results from relative rate experiments indicate that electron-deficient alkenes react slower in ruthenium(II)-catalyzed [2+2] cycloadditions with alkynes.; Ruthenium(II)-catalyzed [2+2] cycloadditions of functionalized alkynes with norbornadiene have also been studied. The cycloadditions were found to be highly stereoselective, affording the exo stereoisomers as the only cycloadducts in poor to good yields (up to 91%). Cp*RuCl(COD) has been demonstrated to possess a high functional group tolerance among substituted acetylenes. Examples of compatible acetylenes include halogenated, carboxylic derivatives, and propargylic alcohol derivatives. Comparative rate findings imply that, generally speaking, electron poor alkynes accelerate ruthenium(II)-catalyzed [2+2] cycloadditions with norbornadiene. Moreover, we have also highlighted the steric limitations between the alkyne component and Cp*RuCI(COD).; Diastereoselective ruthenium(II)-catalyzed [2+2] cycloadditions between symmetrical bicyclic alkenes (norbornadiene and norbornene) and chiral propargylic ethers have also been examined. The cycloadditions afforded the cycloadducts as sole stereoisomers (exo stereochemistry) in moderate to good yields (up to 84%). Moderate levels of diastereoselectivities, up to 4:1, were observed with chiral propargylic ethers.