Aminocatalytic, Stereoselective Synthesis of Tetrahydrocarbazole Spiropyrazolones via Remote [4 + 2] Annulation of Indole Tethered Enal With Olefinic Pyrazolones

Abstract

We present the first application of olefinic pyrazolone in conjunction with indole-tethered enal with an aminocatalytic remote [4 + 2] annulation reaction, successfully yielding tetrahydrocarbazole spiropyrazolone frameworks in moderate to good yields, accompanied by significant enantio- and diastereoselectivities. The robustness of this developed protocol is demonstrated through the generation of a diverse array of 22 examples, all exhibiting consistent yields and stereoselectivities. Furthermore, we achieved a gram-scale synthesis and synthesized the biologically relevant fluorohexahydrofuranocarbazole via a two-pot, three-step sequence involving [4 + 2]-addition, reduction, and fluoroetherification reactions. Finally, we propose a plausible mechanism, supported by SC-XRD and NOE experiments, highlighting a crucial aspect of this research.