[3+3] Cycloadditions of Azomethine Ylides with Nitrile Imines for the Synthesis of 2,3,4,5‐Tetrahydro‐1,2,4‐Triazine‐5‐Carboxylates

Abstract

An unprecedented and efficient [3 + 3] cycloaddition of azomethine ylides with nitrile imines has been achieved. A series of 2,3,4,5-tetrahydro-1,2,4-triazine-5-carboxylates were obtained in moderate to excellent yields. Notable features of this reaction include readily accessible reagents, broad substrate scope (34 examples), mild reaction conditions and operational simplicity.

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations

“…Experimental procedures and characteristic data for all synthesized compounds are given in the Supplementary Information [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

Synthesis of 5‐Trifluoromethyl‐1,4‐dihydro‐1,2,4‐triazines via Base‐mediated [3+3] Cycloaddition of Nitrile Imines and CF3‐Imidoyl Sulfoxonium Ylides

“…For instance, Werz and co‐workers reported a Lewis acid‐catalyzed [3+3]‐cycloaddition of donor‐acceptor cyclopropanes with in‐situ generated nitrile imines for affording tetrahydropyridazines (Scheme 1a) [9] . Recently, Liu and co‐workers developed a base‐mediated [3+3] cycloaddition of azomethine ylides with nitrile imines for the synthesis of unnatural cyclic amino acids containing 1,2,4‐triazines in moderate to good yields (Scheme 1b) [10] . Yu, Zhao and co‐workers demonstrated an efficient dearomatization of 3‐(2‐isocyanoethyl)indoles with nitrile imines via a nucleophilic/Friedel–Crafts/aza‐Mannich type cascade and 1,3‐dipolar cycloaddition reaction to afford polycyclic indoline scaffolds (Scheme 1c) [11] .…”

“…Based on the previously reported literatures of nitrile imines and TFISYs, [9–10,13a,b] a plausible mechanism of this cyclization reaction involving a concerted or stepwise annulation process was proposed as illustrated in Scheme 2. First, nitrile imine A was in‐situ generated from hydrazonyl chlorides 1 in the presence of base.…”

“…[9] Recently, Liu and co-workers developed a base-mediated [3 + 3] cycloaddition of azomethine ylides with nitrile imines for the synthesis of unnatural cyclic amino acids containing 1,2,4-triazines in moderate to good yields (Scheme 1b). [10] Yu, Zhao and coworkers demonstrated an efficient dearomatization of 3-(2-isocyanoethyl)indoles with nitrile imines via a nucleophilic/Friedel-Crafts/aza-Mannich type cascade and 1,3-dipolar cycloaddition reaction to afford polycyclic indoline scaffolds (Scheme 1c). [11] Considering the unique amphiphilic reactivity of nitrile imines, developing more reaction patterns involving nitrile imines with other types of dipolarophiles could greatly enrich the structural diversity of the obtained heterocyclic products.…”