Investigations On The Functionalization Of Heteroatom-Substituted Acetylenes

The prevalence of1,1-or1,2-difunctionalized alkenes as synthons for the elaboration of multisubstituted alkenes renders them one of the most important building blocks in organic chemistry. As such, it is highly desirable to develop new methods to assemble1,1-or1,2-difunctionalized alkenes. In this dissertation, we describe some regio-and stereoselective approaches to1,1-or1,2-difunctionalized alkenes from hetereoatom-substituted alkynes using nucleopalladation or hydrohalogenation reaction.Firstly, a Pd-catalyzed regio-and stereoselective assembly of (1Z)-or (1E)-1,2-dihalo-1,4-dienes has been developed by the haloallylation of haloalkynes. In our opinion, the regiochemistry is controlled by the introduction of heteroatoms, and the stereochemistry is tuned by simply adding stoichiometric lithium halides and the choice of solvents. It is a significant advance in the halopalladation reaction because it realizes the regio-and stereoselective halopalladation of electron-rich internal alkynes for the first time.Secondly, a Pd-catalyzed coupling of haloacetylenes with allyl acetate has been developed, allowing a simple and convenient access to (Z)-β-haloenol acetates in good yields and excellent stereoselectivities. It turns out that the utilization of4,4’-dimethoxy-2,2’-bipyridine can help to improve the reaction yield and selectivity. The synthetic advantages of this method is well demonstrated by the construction of functionalized enol acetates via the Suzuki or Sonogashira coupling of the resultant (Z)-β-haloenol acetate products.Finally, we focus on the investigations of the hydrohalogenation of acetylenic thioether. A cis-hydrohalogenation of akynyl thioether has been realized, giving rise to a- halo vinyl sulfides in good yields with excellent regio-and stereoselectivities. Notably, by taking advantage of the different reactivity of C-X and C-S bonds in the cross-coupling reactions, an operationally simple and general protocol for the production of stereodefined trisubstituted olefins from α-halo vinyl sulfides has been developed, thus providing a novel procedure for the synthesis of trisubstituted alkene containning natural products.