Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

Abstract

An efficient and alternative synthetic approach has been developed to prepare various N-(arylethyl)piperazine-2,6-diones from 4-benzenesulfonyliminodiacetic acid and primary amines using carbonyldiimidazole in the presence of a catalytic amount of DMAP at ambient temperature. Piperazine-2,6-diones are successfully transformed to pharmaceutically useful pyridopyrazines or pyrazinoisoquinolines and ene-diamides via an imide carbonyl group activation strategy using a Brønsted acid. Subsequent dehydrosulfonylation reactions of the ene-diamides, in a one pot manner, smoothly transformed them to substituted pyrazinones. A concise synthesis of praziquantel (1) has also been achieved through this method.

Cyclization Strategies Using Imide Derivatives for the Synthesis of Polycyclic Nitrogen‐Containing Compounds

“…They also reported the reaction of more unusual hetero‐substituted imides with aryl rings having electron‐donating groups, producing, for instance, 85 e and 85 f . The use of heteroaromatic nucleophiles was also possible, thus allowing the preparation, for example, of 85 g and 85 h [58e] (Scheme 19).…”

“…In this case, the cyclization proceeds smoothly but is limited to the use of aryl moieties having electron‐donor groups, such as in the case of 85 a [58a] . Later, they reported similar transformations being promoted by TfOH [58b–g] . Remarkably, a number of cyclizations became feasible, which had not been possible with the use of other activating agents.…”

Pictet–Spengler-Based Multicomponent Domino Reactions to Construct Polyheterocycles

“…The Pictet–Spengler reaction, discovered in 1911 by Amé Pickett and Theodore Spengler, is originally a cyclization of a phenethylamine 1 and a formaldehyde dimethyl acetal 2 to produce 1,2,3,4-tetrahydroisoquinoline 3 in the presence of hydrochloric acid ( Scheme 1 ). 1 After that, a variety of modified reaction systems for the Pictet–Spengler reaction have been developed for the construction of valuable heterocyclic scaffolds, 2 such as Brønsted acids, 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 Lewis acids, 39 40 41 transition metal catalysts, 42 43 44 45 46 organocatalysts, 26 27 47 48 and enzyme strictosidine synthases. 13 49 Meanwhile, the use of suitably substituted amine derivatives such as β-arylethylamines, tryptamines, or functionalized aromatic amines with an aldehyde or ketone is essential for the progress of the Pictet–Spengler reaction.…”