Highly enantioselective synthesis of functionalized azepino[1,2-a]indolesviaNHC-catalyzed [3+4] annulation

Abstract

The enantioselective [3+4] annulation of 3-formylindol-2-methylmalonates with 2-bromoenals catalyzed by NHCs is described to efficiently synthesise functionalized azepino[1,2-a]indoles.

Enantioselective Catalytic Synthesis of N-alkylated Indoles

“…In recent years, there has been growing interest in the field of N-heterocyclic carbene (NHC) catalysis. The functionalization of the indole core via various NHC-intermediates has been reported by several research groups [36][37][38][39][40]. There are only two articles dedicated to the N-functionalization of indoles [41,42].…”

Synthesis of Azepino[1,2‐a]indole‐10‐amines via [6+1] Annulation of Ynenitriles with Reformatsky Reagent

“…Tricyclic carbolines are usually synthesized by intramolecular cyclization under acidic conditions [8d,10–12] . Recently, useful protocols of synthesis of azepino[1,2‐ a ]indoles were established by some excellent methods using transition metal‐catalyzed reactions of indoles, [13] like RCM method using Grubbs II catalysts, [14] Pauson‐Khand type reactions, [15] one pot sequential processes from the haloalkyl indoles with aryl halides, [16] the intermolecular [5+2], [17] and [4+3] cyclization reactions [18] . However, most of the present methods are not suitable for the synthesis of their amine analogs.…”

Insight into the organocatalytic arylation of azonaphthalenes with α-chloroaldehydes: the general mechanism and origin of selectivities

“…Lewis base, Brønsted base (BB) and hydrogen bond donor/acceptor) to promote the rearomatization process, which is remarkably different from the traditional role of the NHC catalyst as a Lewis base (LB) in one system. Due to the reliability of density functional theory (DFT) on the mechanistic studies of organocatalytic [21][22][23][24][25][26] and transition metal-catalyzed reactions, [27][28][29][30] we performed DFT calculations at the M06-2X 31,32 For the stereoselectivity-determining step, the nucleophilic addition of M4 to azonaphthalene R2 first undergoes C-C bond formation via four diastereoselective transition states TS5RR/ RS/SR/SS to generate intermediates M5RR/RS/SR/SS, respectively. As shown in Scheme 2, the two letters after the names represent the molecular chirality associated with the chiral C1 and C2 atoms, respectively.…”