Research in our laboratory is directed toward the development of synthetic methodologies based on the inherent reactivity of alkyne that enable the total synthesis of complex bioactive molecules. Currently, synthetic methodology development in our group is primarily focused on four different activation modes of alkyne, such as hetero-atom activation (ynamide chemistry), triazole pre-activation, transition metal activation and the transient isomerization. We also enjoy the opportunity to utilize our own-developed methodology in complex bioactive natural product total synthesis.
we have developed a cascade reaction that includes NBS-mediated addition of allyl alcohols to ynamides, Claisen rearrangement, and dehydrobromination, providing a simple and efficient route to (2Z)-2,4-dienamides, a type of useful intermediate in organic synthesis.
We have developed a rhodium-catalyzed intramolecular [3 + 2] cycloaddition with N-sulfonyl-1,2,3-triazoles as the 1,3-dipole precursor, which showed excellent stereoselectivity and allowed for a quick access to the scaffold of Aspidosperma- and Kopsia-related alkaloids. Based upon its operational simplicity and the mild reaction conditions, the current approach may open up a new and efficient access to an array of valuable indole alkaloid analogues. The total synthesis towards the related alkaloids is ongoing.
Transition metal activation
We developed a palladium-catalyzed cascade cycloaddition/cyclization reaction of ortho-alkynylbenzaldehydes giving products containing the [2.2.2] bicyclic lactone core structural unit found in chaetophelnol C which was isolated in 2013 from epigenetic manipulated Chaetomium indicum by Oshima and co-workers. The new reaction not only leading to a one-step construction of tetracyclic core structure of chaetophenol C but also providing its correctly placed functionality from two simple starting materials under very mild condition. The developed chemistry was also successfully applied to the first total synthesis of chaetophenol C and dozens of its analogs.
We have developed a new, metal-free, and one-pot synthetic route to substituted pyridines, which employs a cascade reaction sequence from an α,β-unsaturated ketone and a phosphazene (both produced in situ), involving an aza-Wittig, a 6π-3-azatriene electrocyclization reaction, and a [1,3]-hydrogen shift. Based upon advantages such as simple operation, broad functionality tolerance, and significance of the multisubstituted pyridine products, this method provide a significant potential in organic synthesis. Recently, the total synthesis of three pyridine-containing natural products including suaveoline, norsuaveoline and normacrophyline was achieved in our lab by using our own-developed methodology.
Natural Product Total Synthesis
We have also working on strategy-enabling natural product total synthesis. Some selected targets are shown as above. Recently, we have accomplished the total synthesis of arboridinine.