An efficient synthesis of pyrido[1,2-a]indoles through aza-Nazarov type cyclization

Abstract

Transition metal free Brønsted acid mediated synthesis of biologically important pyrido[1,2-a]indole scaffolds through aza-Nazarov type cyclization of readily available diaryl(2-pyridyl)methanol using formic acid has been developed. This methodology has been successfully extended to synthesize atropisomers.

An Unprecedented Family of Luminescent Iridium(III) Complexes Bearing a Six-Membered Chelated Tridentate C^N^C Ligand

“…Litt. 54 : 156 °C. 1 H NMR (400 MHz, CDCl 3 ): δ 8.58 (d, J = 3.2 Hz, 1H), 7.67–7.60 (m, 1H), 7.33–7.28 (m, 4H), 7.24–7.12 (m, 6H), 6.19 (s, 1H), 1.30 (s, 18H).…”

Aza-Nazarov Cyclization Reactions via Anion Exchange Catalysis

“…12b Cyclization reactions of pyridine-containing triarylmethanols to pyrido[1,2-a]indoles were achieved by the Klumpp and Sekar groups with the use of TfOH and formic acid, respectively. 13,14 To our knowledge, the only catalytic enantioselective aza-Nazarov reaction to date was reported by the Tius group in 2010. 15 In this work, the racemic azirine reactant 4 was found to undergo an organocatalytic aza-Nazarov reaction in the form of a kinetic resolution to afford enantiomerically pure product 6 after a ring expansion reaction (Scheme 1c).…”

A pyrone remodeling strategy to access diverse heterocycles: application to the synthesis of fascaplysin natural products

“…To demonstrate the viability of this strategy, we initially focused on converting indole-pyrone adduct 3 to the pyrido[1,2a]indole scaffold (3b, Scheme 2a)-a key structural motif 1b present in a number of biologically active natural products including fascaplysin (4, Scheme 2b), 10 goniomitine (5), 11 and tronocarpine (6). 12 While there exists numerous methods to access this biologically relevant scaffold, [13][14][15][16][17] many of these tactics rely on reaction precursors with highly specific substitution patterns and, therefore, are unfortunately not general or modular. Specifically, we recognized that while heterocyclic-dienolate adducts (such as C3-substituted intermediate 3a) have proven to be effective precursors for benzannulation processes, strategies to install dienol/dienolate functionality at C2 of 1H-indoles lacking C3-substitution have remained elusive due to regioselectivity challenges.…”