N-Heterocyclic Carbene Catalyzed Intramolecular Hydroacylation Of Alkynylphosphonates And Related Domino Reactions

Organic phosphorus compounds are attractive to chemists due to their wide biological activities and catalytic properties in organic synthesis. Moreover, the phosphonyl heterocycles and related compounds have been widely used in the field of Pharmaceuticals and agrochemicals such as bactericides, insecticides, fungicides and plant growth regulators. On the other hand, the broad application of N-heterocyclic carbenes (NHCs) in organic synthesis has been impressively demonstrated, which play a vital role as efficient nucleophilic organocatalysts in a variety of organic reactions. Especially, the NHCs catalyzed the intramolecular hydroacylation of aldehydes with unconventional eletrophiles such as C-C multiple bonds which derivatived from the Stetter reaction and became the latest hotspot in this fild due to the importance in synthesis of natural products and drug intermediates, but the electrophilicity were mainly limited to alkynylones、alkynylesters. In order to extend the substrates of this type reaction, we introducted the alkynylphosphonate to the reaction system. Finally, we have developed an effective organocatalytic intramolecular hydroacylation reaction between phosphonylation alkynyl and formyl group by utilizing N-heterocyclic carbene catalysis.1. After optimization of reaction conditions including catalysts, base, solvents etc., we finally radicated the optimal reaction system. Also Two exocyclic and endocyclic olefin tautomers of chromone phosphonates were obtained in good to excellent yields at different room temperatures, and proposed respectively the possible mechanism. The exocyclic olefin tautomer obtained was further reacted with alpha-pyridylmethyl ketone salts in a one-pot procedure to afford benzopyranopyridine derivatives in moderate yield.2. Since α、β-unsaturated kotones can reacted with another molecular of aldehyde in the Stetter reaction. We successfully established the NHCs catalyzed cascade reaction involving the hydroacylation of activated alkynes to obtain a1,4-diketon motif which could reacted with ammonium acetate to obtain polysubstituted pyrrole via one-pot synthesis.