New Application of Pictet−Spengler Reaction Leading to the Synthesis of an Unusual Seven-Membered Heterocyclic Ring System

Abstract

A novel strategy for the Pictet-Spengler reaction is reported. Our strategy involves reaction of arylamines, linked to the N-1 of disubstituted imidazoles, with aldehydes in the presence of p-TsOH. The iminium ion generated in situ undergoes C-C bond formation with the C-5 of the imidazoles to furnish triazabenzoazulenes as a novel heterosystem. Our strategy differs from conventional Pictet-Spengler reaction since the latter utilizes only aliphatic amines in which the amine functionality is linked to a C instead of N of the activated aromatic moiety.

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

“…Recently, the Pictet–Spengler reaction has been successfully extended to arylamine substrates [11–17]. These substrates are designed by replacing the aliphatic amine side chain attached to activated heterocycles, for example tryptamine ( 1 ), by aromatic amines [11].…”

“…These reactions are generally termed as modified Pictet–Spengler reaction [11]. This modification of the conventional reaction led to the synthesis of a polyheterocyclic skeleton that mimics the natural products [12–17]. The 6- endo cyclization is the rate-limiting step in the Pictet–Spengler reaction and electrophilicity of the imine is the driving force of the reaction [1].…”

Lewis Acid‐Catalyzed Selective Synthesis of Diversely Substituted Indolo‐ and Pyrrolo[1,2‐a]quinoxalines and Quinoxalinones by Modified Pictet–Spengler Reaction

“…174-176°C. 1 56 (m, 3 H), 7.52-7.50 (m, 2 H), 7.48-7.44 (m, 1 H), 7.39 (td, J = 5.9, 0.9 Hz, 1 H), 2.08 (s, 3 H) ppm. 13 135.8, 132.0, 130.5, 130.3, 130.1, 129.1, 128.5, 128.1, 125.9, 124.6, 123.1, 122.0,120.7, 114.4, 114.3, 110.8 : To a well-stirred solution of 1-(2-aminophenyl) pyrrole or 2-(3-methylindol-1-yl)phenylamine (1.0 mmol) in toluene (2.0 mL), benzotriazole (1.0 equiv.)…”

“…[7] From a synthetic point of view, the opportunity to prepare complex polycyclic molecules in a limited number steps is an exciting goal for every modern organic chemist. Although a number of methods are available for the synthesis of simple substituted quinoxalines, [8,9] only a limited amount of work has been done on the synthesis of polycyclic quinoxalines, especially indoloquinoxalines.…”

Five‐Membered Heterocycles: 1,3‐Azoles

“…For example, the addition of the iminium ion 106 obtained from the azole-aldehyde 105 and an aryl-piperazinone affords a mixture of 107 and 108 in a 1 : 2 ratio, respectively (Scheme 10.44) [162]. When position 2 is substituted the reaction yields the 4-substituted product [137,163].…”