Abstract
In the quest for new heterocyclic scaffolds exhibiting potentially biological activities for medicinal chemistry, a multicomponent 1,3-dipolar cycloaddition reaction of tetrahydroisoquinolinium N-ylides, generated in situ from cyclic diketones and isoquinoline, and (E)-3-arylidene-1-phenyl-pyrrolidine-2,5-diones has been developed. This route provides workable access to dispiropyrrolo[2,1-a]isoquinoline-fused pyrrolidine-2,5-diones bearing two adjacent spiro-carbons. An unprecedented regioselectivity was observed in this 1,3-dipolar cycloaddition, leading to the construction of a novel dispirooxindole skeleton. The structure and relative stereochemistry of the spiranic adducts have been confirmed by three X-ray diffraction studies. To reinforce the observed regio- and stereoselectivity of the [3+2] cycloaddition, calculations using the DFT approach at the B3LYP/6-31G(d,p) level were carried out. It was found that this reaction affords the kinetic products.
Highlights
Pyrrolo[2,1-a]isoquinolines as structural motifs have drawn considerable interest in the area of synthetic organic chemistry and medicinal chemistry as they represent substructures o en encountered in numerous bioactive natural isolates and pharmaceutically important compounds.[1]
The calculated local chemical reactivity parameters of syn-d2b and dipolarophile 1a are shown in Fig. S1.† We can notice that C-10b0 of azomethine ylide syn-d2 has more nucleophilic character
We have developed an efficient method for the synthesis of a novel class of dispiropyrrolo[2,1-a]isoquinolines fused pyrrolidine-2,5-dione bearing two adjacent spiro-carbons in good to high yields with high diastereoselectivity
Summary
Pyrrolo[2,1-a]isoquinolines as structural motifs have drawn considerable interest in the area of synthetic organic chemistry and medicinal chemistry as they represent substructures o en encountered in numerous bioactive natural isolates and pharmaceutically important compounds.[1]. Scheme 2 Profile of 1,3-dipolar cycloaddition for exocyclic enones with tetrahydroisoquinolinium N-ylides derived from cyclic diketones. Sarra et al.[11] developed the rst examples of multicomponent 1,3-dipolar cycloaddition reaction involving acenaphthenequinone and isatin as cyclic diketones-based tetrahydroisoquinolinium N-ylides with chalcone and nitrostyrene derivatives as dipolarophiles (Scheme 1, eqn 2 and 3).[11] The azomethine ylides were produced in situ via [1,5]-H shi and subsequent deprotonation.
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