A Serendipitous Non‐Metal‐Mediated Sp3 C─H Functionalization of 2‐Methyl Indolyl Scaffold for the Synthesis of 2‐Alkenyl Indoles*

This work presents an innovative strategy for C─H functionalization of sp³ carbon, enabling the efficient synthesis of 2-alkenyl indole scaffolds, a bioactive olefins. This study broadens the scope of C─H functionalization by employing previously unexplored starting materials, such as C3-alkylated 2-methylindole and benzaldehydes, offering new possibilities in organic synthesis. This transformation is effectively driven by NH₄Cl and MgSO₄, ensuring outstanding selectivity with broad substrate scope, high efficiency, and excellent yields under mild reaction conditions.

Abstract

Challenging conventional methodologies, we pioneer a groundbreaking approach by C─H functionalization of sp³ carbon, which leads to the effective synthesis of 2-alkenyl indole scaffold, bioactive olefin. Our study introduces an innovative approach by utilizing previously unexplored starting materials, expanding the possibilities of C─H functionalization. In contrast to previous studies that rely on metal-based catalysts, our strategy harnesses a cost-effective and environmentally friendly method. This functionalization was effectively promoted by NH₄Cl and MgSO₄, ensuring high efficiency, exceptional selectivity, and excellent yields under mild conditions. A series of spectroscopic techniques, including NMR (¹H, ¹³C, 19F, and DEPT-135), IR, and mass spectrometry, were used for the detailed characterization of the synthesized 2-alkenyl indoles. This method not only demonstrates broad functional group compatibility but also establishes a sustainable alternative to traditional metal-catalyzed processes. By redefining the scope of this reaction, our work paves the way for future advancements in organic synthesis and biomedical applications.

Zum Volltext