N-Alkylation-Initiated Redox-Neutral [5 + 2] Annulation of 3-Alkylindoles with o-Aminobenzaldehydes: Access to Indole-1,2-Fused 1,4-Benzodiazepines

Abstract

Described herein is an unprecedented N-alkylation-initiated redox-neutral [5 + 2] annulation of 3-alkylindoles with o-aminobenzaldehydes via a cascade N-alkylation/dehydration/[1,5]-hydride transfer/Friedel–Crafts alkylation sequence. A series of indole-1,2-fused 1,4-benzodiazepines are facilely constructed in moderate to good yields in one step. This protocol features excellent regioselectivity, metal-free conditions, high step economy, and wide substrate scope.

Access to Polycyclic Indole-3,4-Fused Nine-Membered Ring via Cascade 1,6-Hydride Transfer/Cyclization

“…This speculation was further verified by the formation of [D]- 3a ′. On the basis of the above investigation and our precedent works, − the following mechanism is proposed for the construction of indole-3,4-fused 3a (Scheme ). Initially, the condensation of secondary amine with aldehyde produced the iminium ion I , which induced the subsequent 1,3-HT between the two benzylic C–H bonds to furnish the isomerized iminium ion II .…”

“…As a continuous interest in one-step assembly of molecular complexity via HT strategy, − recently, we reported the construction of spiro-indoles and indole-1,2-fused seven-membered indolodiazepines through rational design of the indole-based cascade 1,5-HT/cyclization. On the basis of that, herein, we report a novel cascade aldimine condensation/1,6-HT/Mannich-type cyclization for one-step construction of indole-3,4-fused nine-membered rings.…”

HOAc catalyzed three-component reaction for the synthesis of 3,3′-(arylmethylene)bis(1H-indoles)

“…The past several decades have witnessed the revival of heterocyclic chemistry, especially in the synthesis of nitrogen heterocycles. 1–4 Indoles are an important class of nitrogen-containing heterocyclic compounds because of their significant biological activities, such as anticancer, 5 progesterone receptor antagonist, 6 anti-inflammatory, 7 and antiviral activities, among others. 8 Thus the construction as well as the modification of the indole ring has attracted much attention from chemists.…”

Modular and Stereoselective Approach to Highly Substituted Indole/Pyrrole-Fused Diazepanones

“…In 2018, Uchuskin’s group reported a one-pot synthetic method for pyrrole-fused 1,4-diazepanones based on the condensation of N -Boc amino acids with furans containing aminoalkyl groups . Recently, Xiao’s group developed an N -alkylation-initiated redox-neutral [5+2] annulation of 3-alkylindoles with o -aminobenzaldehydes via a cascade N -alkylation/dehydration/[1,5]-hydride transfer/Friedel–Crafts alkylation sequence to access indole-1,2-fused 1,4-benzodiazepines . Despite this progress, more efficient and straightforward synthetic strategies for such heterocyclic scaffolds are still highly desirable.…”