Synthesis of Hydrocarbazole Derivatives by Oxidative Dearomative Cyclization of Diarylamines using a Hypervalent Iodine Reagent

Abstract

Hydrocarbazole derivatives bearing a quaternary stereogenic center at C4a were synthesized by means of intramolecular oxidative dearomatization of diarylamines using hypervalent iodine in moderate to good yields. The hydrocarbazole bearing a cyclohexadienone moiety was further converted into the tetracyclic skeletons of Aspidosperma and akuammiline-type alkaloids via regioselective aza-Michael reaction at C4 and at C9a, respectively.

Total Synthesis of Fused Polycyclic Alkaloids Based on Oxidative Phenolic Couplings and Aza-Michael Reactions

“…Thus, we found suitable reaction conditions for selective synthesis of the two regioisomers, which are key synthetic intermediates for aspidosperma-type and vincorine-type MIAs, respectively. [14] Template for SYNLETT Thieme…”

“…Thus, we found suitable reaction conditions for the selective synthesis of the two regioisomers of these key synthetic intermediates. 14…”

Recent Advances in Synthetic Strategies for the C4a,C9a-Fused Tetracyclic Hydrocarbazole Core Structure of Minfiensine and Related Akuammiline Alkaloids

“…2 In 2020, our group reported a synthesis of tetracyclic hydrocarbazole 70 from dienone 68, which was obtained from oxidative dearomative cyclization of diarylamine 67 with hypervalent iodine agent (Scheme 12). 45 Specifically, oxidative dearomative cyclization of diarylamine 67 bearing an ethylamino group using diacetoxy iodobenzene (PIDA) in hexafluoro-2-propanol (HFIP) afforded dienone 68 in 40% yield. The aza-Michael reaction products at C9a 71 and C4 72 were each selectively obtained from 68 under different acidic conditions (TFA and HCl, respectively).…”

Diels‐Alder Cycloaddition of Azepino[4,5‐b]indoles Towards Hydrocarbazole Derivatives and Related Heterocycles

“…In the past few years, due to the importance of assembly of the hydrocarbazoles bearing an all‐carbon quaternary center at C4a position, many elegant synthetic strategies have been developed on the basis of dearomative cyclization, [2e–f,5] Heck cyclization, [6] Fischer indolization, [7] aza‐Michael addition [8] and cycloaddition of indole derivatives (Scheme 1). [9] Although these efforts have greatly enriched the toolbox for the construction of hydrocarbazoles, the development of an expeditious and efficient strategy for the preparation of compounds bearing hydrocarbazole scaffolds is urgently in need to access more potent bioactive molecules.…”