Research Projects

Tetrasubstituted olefins are widely found in natural products (for example: Nileprost analogues or epi-Illudol), drugs (such as Tamoxifen, Vioxx, and their derivatives), and other biologically active substances. Thus, the development of an efficient and eco-friendly strategy for the construction of tetrasubstituted olefins is always desirable. In general, the tetrasubstituted olefins are synthesized via 1,2-difunctionalization of symmetrical and unsymmetrical alkynes with the aid of transition-metal catalysts. Despite the synthetic methods available for the difunctionalization of unactivated alkynes, the studies related to difunctionalization electron rich alkynes, such as N-bearing alkyne (ynamide) remains unknown. The inherent polarization of N-lone pair to the alkyne makes the ynamide charged; thus, oxidative insertion of carbometalic species to ynamide is challenging. The current proposal delineates a transition-metal catalyzed 1,2-difunctionalization of ynamide by the addition of two distinct functional groups across CC multiple bonds. The reaction presumably involves oxidative addition and insertion reaction across the C-C multiple bonds of ynamide to produce the vinyl-organometallic species. Finally, quench of vinyl-organometallic species with a nucleophile/electrophile under the specific conditions to give the desired difunctionalized product. The proper coordination of three significant steps: (I) oxidative insertion of low valent transition metal to organic electrophile in presence of charged ynamide, (II) direct insertion of organometallic species to ynamide for the formation of vinylic-metal species, and (III) the quench of vinyl metal species with respective nucleophile/electrophile can make the proposed transformation viable, which to our knowledge is challenging. The merge of two different bond-forming processes makes the overall process atom- and step-economic. This three-component reaction would finally construct a wide range of highly functionalized unusual tetrasubstituted enamide products. This synthetic method would be further extended unraveling novel synthetic transformations using two different metal catalysts (Dual Catalysis).