Multicomponent Cascade Reactions and Skeletal Rearrangements of Isatins for the Synthesis of Functionalized
Jia-Qi Shao1, Rong Huang1, Long-Kun Chen1
1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, P. R. China.
Abstract:
This study developed a novel and efficient method for the synthesis of structurally diverse pyrrolo[1,2-c]quinazolin-5(6H)-ones (4). The method involved an unprecedented multicomponent cascade reaction of isatins (1), chromone-3-carboxaldehydes (2), and ammonium acetate (3) in N,N-dimethylformamide, with pivalic acid serving as the promoter. Under simple reflux conditions, this one-pot transformation readily affords highly functionalized derivatives 4 through the formation of four new bonds (three C-N and one C═C) as well as the cleavage of two bonds (one C-C and one C-O). The method exhibited broad substrate scope and versatility, enabling access to a wide range of pyrrolo[1,2-c]quinazolin-5(6H)-ones suitable for combinatorial and parallel synthesis of natural product-like pyrroloquinazolinone derivatives. Key advantages of this method include the use of readily available starting materials, atom-efficient transformation, efficient skeletal rearrangement, and the potential for generating bioactive molecular frameworks.
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