Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 310058, Hangzhou, China.
Laboratory of Organic Chemistry, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Nat Commun. 2020 Nov 6;11(1):5639. doi: 10.1038/s41467-020-19467-5.
Skeletal reorganization is a type of intriguing processes because of their interesting mechanism, high atom-economy and synthetic versatility. Herein, we describe an unusual, divergent skeletal reorganization of N-sulfonyl ynamides. Upon treatment with lithium diisopropylamine (LDA), N-sulfonyl ynamides undergo a skeletal reorganization to deliver thiete sulfones, while the additional use of 1,3-dimethyl-tetrahydropyrimidin-2(1H)-one (DMPU) shifts the process to furnish propargyl sulfonamides. This skeletal reorganization divergence features broad substrate scope and scalability. Mechanistically, experimental and computational studies reveal that these processes may initiate from a lithiation/4-exo-dig cyclization cascade, and the following ligand-dependent 1,3-sulfonyl migration or β-elimination would control the chemodivergence. This protocol additionally provides a facile access to a variety of privileged molecules from easily accessible ynamides.
骨架重排是一类引人入胜的过程，因为它们具有有趣的机制、高原子经济性和合成多功能性。在此，我们描述了 N-磺酰基炔酰胺的一种不寻常的、发散的骨架重排。用二异丙基氨基锂（LDA）处理时，N-磺酰基炔酰胺发生骨架重排，生成噻吩硫酮，而额外使用 1,3-二甲基四氢嘧啶-2(1H)-酮（DMPU）则会使反应转变为炔丙基磺酰胺。这种骨架重排的发散具有广泛的底物范围和可扩展性。从机理上看，实验和计算研究表明，这些过程可能源于锂化/4-endo-dig 环化级联，随后的配体依赖性 1,3-磺酰基迁移或β-消除会控制化学发散。该方案还提供了一种从易得的炔酰胺中获得各种优势分子的简便方法。
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