NIS Mediated Cross-Coupling of C(sp²)–H and N–H Bonds: A Transition-Metal-Free Approach toward Indolo[1,2-a]quinazolinones

Abstract

A metal- and base-free protocol for intramolecular cross-coupling of C(sp)-H and N-H bonds using N-iodosuccinimide (NIS) has been demonstrated. This environmentally benign approach furnishes a series of substituted indolo[1,2-a]quinazolinones from the suitably fabricated indoles via C-N bond forming cyclization in 28-82% yield. A plausible mechanism is proposed for this cyclization based on the results of a control experiment. This methodology requires no additional metal catalyst, oxidant, or base. Furthermore, the synthetic utility of the protocol is demonstrated by performing a gram scale reaction.

Catalyst and Additive‐Free Direct Amidation/Halogenation of Tertiary Arylamines with N‐haloimide/amides

“…N-iodosuccinimide (NIS)-promoted methods have been successfully applied for crossdehydrogenative coupling (CDC) or oxidative CÀ N cross-coupling reactions. [13] Recently, 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)-activated N-bromosuccinimide (NBS) has been utilized in CÀ N bond formation. [14] Amides are one of the most-important functional groups in life and are present in many biologically active compounds.…”

“…Because bases may promote the deprotonation of methyl hydrogen, [24] various inorganic and organic bases were tested (Table 1, entries [11][12][13][14][15][16][17]. However, no obvious improvement to the reaction outcome was found, and moderate-to-good yields were achieved in most bases.…”

N-Halo Reagents: Modern Synthetic Approaches for Heterocyclic Synthesis

“…A greener approach to indolo[1,2-a]quinazolinones 326 was developed by Badigenchala and Sekar, who reported a metal-and base-free NIS-mediated protocol for the crosscoupling of C(sp 2 )-H and N-H bonds (Scheme 80). 146 The…”

“…In further probing the efficiency of this new metal-free C-N cross-coupling protocol, a gram-scale experiment was successfully performed under standard conditions, affording the product in 78% yield. 146…”

Copper‐Catalyzed Synthesis of 5‐Arylindolo[1,2‐c]quinazolin‐6(5H)‐ones from 2‐(2‐Bromoaryl)indoles and Aryl Isocyanates under Microwave Irradiation

“…Many synthetic methods of indole‐ or quinazolinone‐containing compounds have been developed due to their broad biological activities [1,2] . However, limited synthetic examples of indole‐fused quinazolinones, indolo[1,2‐ c ]quinazolin‐6(5 H )‐ones shown in Scheme 1 are known [3,4] . Indolo[1,2‐ c ]quinazolin‐6(5 H )‐one itself can be synthesized by Fisher indolization of phenylhydrozone prepared from 2‐aminoacetophenone and phenylhydrazine followed by cyclization with phosgene (Scheme 1, route a) [5] .…”