Synthesis of Functionalized Indole- and Benzo-Fused Heterocyclic Derivatives through Anionic Benzyne Cyclization

Apparent Alkyl Transfer and Phenazine Formation via an Aryne Intermediate

“…17 Barluenga et al exploited the use of benzyne-tethered vinyl or aryl lithium compounds to obtain indole and benzo-fused heterocyclic derivatives. 18 The reactivity of aryne intermediates toward nucleophilic attack is attributed to the low energy LUMO, which is a consequence of the "bending" of the triple bond within the ring; decreasing the energy gap between the LUMO of the aryne and the HOMO of the attacking nucleophile enables reaction between the two partners. 19 For generating benzyne intermediates, a well-established method involves treating an aryl halide with a strong base, especially alkali metal aryls/alkyls or amides in ether solvents or liquid ammonia.…”

Regioselective Synthesis of Elusive 4,9-Dihydro-1H-Carbazoles by Gold-Catalyzed Cycloisomerization of 3-Allenylmethylindoles

“…Remarkably, a switch in the regioselectivity occurred using an equimolecular mixture of PPh 3 AuCl and AgNTf 2 as catalyst (entry 5). Analogous experiments using catalysts derived from NHC or phosphite ligands also produced cycloadduct 2a as the major isomer in comparable ratios (entries [7][8][9]. The switch in the regioselectivity (entry 1 vs 5) could be associated with a non innocent presence of the silver salt.…”

“…[3][4][5] Therefore, numerous approaches for their preparation have been described. 1 However, the synthesis of the related tetrahydro- [6][7][8][9] and dihydrocarbazoles [10][11][12][13] has received less attention. For instance, no efficient methodologies to access 4,9-dihydro-1H-carbazoles have been developed, even though this heterocyclic skeleton is found in diverse natural products such as dihydrotubingensins A-B (Figure 1).…”

4.09 Nucleophilic Coupling with Arynes

“…270,271 In addition, a variety of dibenzoheterocyclic structures can be constructed efficiently by intramolecular aryl-aryl bondforming processes through the aryne cyclization (equation 28), 272,273 and the synthetic utility of this methodology has been demonstrated by total synthesis of trisphaeridine (115,Scheme 94) and N-methylcrinasiadine (116, Scheme 95). 274 Extensive studies have been conducted on the cyclization using stabilized carbanions containing imine, 275,276 sulfonyl, 277 or phosphinyl moiety, 278,279 that give indole, benzocyclobutene, or isoindolinone derivatives, respectively (Scheme 96).…”