Synthesis of 1,7-Fused Indolines Tethered with Spiroindolinone Based on C–H Activation Strategy with Air as a Sustainable Oxidant

Abstract

Herein, we present an efficient synthesis of 1,7-fused indolines tethered with a spiroindolinonyl moiety through the cascade reaction of indolin-1-yl(aryl)methanimines with diazo oxindoles. To the best of our knowledge, this is the first example in which 1,7-fused indoline skeleton was constructed along with the simultaneous introduction of a spiro element initiated by the C−H bond activation of indoline. In forming the title product, the indoline substrate and the diazo coupling partner demonstrated an unprecedented reaction pattern in which the latter acts as a C1 synthon to participate in the construction of the spirocyclic scaffold through the reductive elimination of a key seven-membered Ru(II) species by using air as an effective and sustainable oxidant to regenerate the active catalyst. Moreover, studies on the cytotoxicity of selected products against several human cancer cell lines demonstrated their potential as lead compounds for the development of anticancer drugs. With notable features such as simple and economical substrates, pharmaceutically valuable products with sophisticated spirocyclic skeleton, mild reaction conditions, cost-free and sustainable oxidants, high efficiency, excellent compatibility with diverse functional groups, and scalability, this method is expected to find wide applications in related areas.

Recent approaches for the synthesis of heterocycles from amidines via a metal catalyzed C–H functionalization reaction

“…In this reaction, diazo oxindoles play the C1 synthon role and meanwhile N 2 is released as a harmless byproduct. 35 Based on the obtained products, classical coupling reactions can be reasonably applied and compounds with more complex structures are synthesized (Scheme 22).…”