Syudy On Copper-catalyzed Heterocycle Synthesis With Propargyl Acetates

Propargylic moieties occur frequently in natural products, synthetic pharmaceuticals and fine chemicals, as well as synthetic intermediates in organic synthesis. A range of metal catalysts can activate alkyne and the attack by nucleophilic reagent realizes various chemical transformations. We report microwave assisted and copper-catalyzed synthesis of two kinds of heterocycles based on the activation of propargyl acetates:(1) the synthesis of furocoumarins and dihydrofurocoumarins from corresponding 4-hydroxycoumarins and propargyl acetates; (2) the synthesis of fully substituted pyrroles from β-enamino compounds and propargyl acetates.The furo[3,2-c]coumarin (4H-furo[3,2-c]chromen-4-one) framework is always present in many medicinally important compounds with a wide variety of biological activities. Consequently, the efficient construction of furo[3,2-c]coumarins from readily available starting materials has attracted much attention. Although several approaches have already been developed for the synthesis of furo[3,2-c]coumarin analogues, these protocols have the drawbacks of requiring multiple steps, expensive metal catalysts or a limited range of substituents. In the current study, we have developed a novel copper-catalyzed and microwaved-promoted process for the construction of furo[3,2-c]coumarins from 4-hydroxycoumarins and terminal propargyl acetates in moderate to good yields (up to 80% yield) through a propargylation/alkyne oxacyclization/isomerization cascade. By using 1,2-dichloromethane as the solvent instead of dimethyl sulfoxide, a range of 2-methylenedihydrofuro[3,2-c]coumarins could be obtained as the major products (up to 85% yield).Fully substituted pyrroles are important bioactive motifs and are found fre quently in many biologically active compounds and natural products. The great importance and potent bioactivity suggest the need for simple and efficient m ethods to construct these molecules, especially the convenient one-step synthesis of fully substituted pyrroles. Thus, we have developed an efficient synthesis of pentasubstituted pyrroles under microwave irradiation. A series of pyrroles, espe-cially a-arylpyrroles, with variation on all the positions of ring could be obtai-ned in moderate to good yields (up to 93%) through a tandem propargylation/a-lkyne azacyclization/isomerization sequence from (3-enamino compounds and pr-opargyl acetates.