Metal‐Free Dehydrogenative Diels–Alder Reactions of 2‐Methyl‐3‐Alkylindoles with Dienophiles: Rapid Access to Tetrahydrocarbazoles, Carbazoles, and Heteroacenes

Abstract

An unprecedented strategy for in situ generation of indole-based ortho-quinodimethanes (oQDMs) from 2-methyl-3-alkylmethylindoles by either a metal-free DDQ- or BQ-mediated dehydrogenative process was developed. These oQDMs were trapped by electron-deficient dienophiles to provide a facile approach to synthetically valuable tetrahydrocarbazoles, carbazoles, and hetereoacenes. The salient features of this transformation include direct C(sp(3))-H bond functionalizations, readily available starting materials, metal-free conditions, high efficiency, operational simplicity, and ease of scale-up.

Copper-Catalyzed Dehydrogenative Diels–Alder Reaction

“…Moreover, a few examples on dehydrogenative Diels–Alder reactions have emerged as unique protocols for the one-step construction of unsaturated six-membered carbocycles. One such case is via Pd, Pt/C-catalyzed, or oxidative dehydrogenation to generate reactive diene intermediates (Scheme ), which was reported by White, Porco, Ishihara, Zhang, and others . Another example developed by Porco and co-workers is an Rh/C-catalyzed dehydrogenative reaction of cyclopentanone derivatives to form very reactive cyclopentadienone dienophiles .…”

Cyclopenta[b]annulation of Heteroarenes by Organocatalytic γ′[C(sp3)−H] Functionalization of Ynones

“…In an effort to expand our studies on the organophosphine‐catalyzed cyclopentannulations, we envisioned that the zwitterionic intermediate B could be generated by the conjugate addition of a phosphine to the ynone A , Scheme b. Intramolecular 1,5‐proton migration from the ideally situated benzylic C(sp 3 )−H could furnish heteroaryl‐based ortho ‐quinodimethane (oQDM) C . In this context, it is worth mentioning the existing metal‐free approaches developed by Melchiorre (trienamine‐mediated organocatalysis), Chi (N‐heterocyclic carbene catalysis), and Zhang for the generation of heteroaryl‐based oQDMs . The underlying concept in these studies is that the in situ generated oQDM intermediates undergo a typical [4+2]‐cycloaddition reaction to afford heteroarenes annulated with six‐membered rings.…”

Organocatalytic γ′[C(sp3)–H] Functionalization of Ynones: An Unusual Approach for the Cyclopentannulation of Benzothiophenes

“…13 However, metal-free and directing group-free activation of benzylic C(sp 3 )-H has been realized only recently through the pioneering trienamine-mediated organocatalytic approaches elucidated by Jørgensen, Chen, and Melchiorre (Scheme 2, a). 14 Further, Chi and Xu's N-heterocyclic carbene (NHC)-catalyzed benzylic C(sp 3 )-H functionaliza- tions (Scheme 2, b), 15 and Zhang's metal-free dehydrogenative cyclization pathways (Scheme 2, c) 16 contributed enormously to the advancement of this area. The underlying concept in these studies is that the in situ generated heteroaryl-based ortho-quinodimethane (oQDM) intermediates undergo a typical [4+2] cycloaddition reaction to afford heteroarenes annulated with six-membered rings.…”