Synthesis and Mechanistic Study of Cyclic Oxoguanidines via Zn(OTf)₂‐Catalyzed Guanylation/Amidation from Readily Available Amino Acid Esters and Carbodiimides

Abstract

The Zn(OTf)2 -catalyzed guanylation/amidation from readily available amino acid esters and carbodiimides is achieved to provide efficiently various cyclic oxoguanidines, including 2-amino-1H-imidazol-5(4H)-ones and 2-aminoquinazolin-4(3H)-ones in medium-to-high yields. It is the first time that an ammonium salt has been used in a guanylation reaction. The application of cyclic oxoguanidines to provide the conjugated heterocyclic compounds via oxidative C-N formation or aldol reaction is explored. The reaction mechanism is well elucidated by the isolation and characterization of three important intermediates.

RE[N(SiMe3)2]3-Catalyzed Guanylation/Cyclization of Amino Acid Esters and Carbodiimides

“…On the basis of the mechanism raised by Zhang and evidence from the 1 H NMR experiment mentioned above, we propose a possible mechanism for the current transformation, shown in Scheme . The aminolysis of rare-earth metal amide RE­[N­(TMS) 2 ] 3 with ethyl 2-aminobenzoate would generate intermediate A .…”

“…Recently, novel pathways have been explored to construct quinazolinones starting with amino acid ester and cyanamide, isothiocyanate, or thiourea . Xi and Zhang developed a Zn-catalyzed tandem guanylation/amidation of amino acid esters, in which carbodiimides were used instead …”

Ph3P/I2-Mediated Synthesis of N,N′,N″-Substituted Guanidines and 2-Iminoimidazolin-4-ones from Aryl Isothiocyanates

“…Thus far, both solid-phase and solution-phase syntheses of 2-iminoimidazolin-4-one derivatives have been reported. These approaches involved the formation of carbodiimide intermediate prior to an intramolecular cyclization as summarized in Scheme .…”

A binuclear aluminium complex as a single competent catalyst for efficient synthesis of urea, biuret, isourea, isothiourea, phosphorylguanidine, and quinazolinones

“…[36][37][38][39][40] Synthesis of quinazolinones generally needs long and tedious reaction steps with the use of toxic reagents. Therefore, novel and efficient catalytic systems involving earth-abundant, environment-friendly, non-toxic metals and substrates are highly demanded for the construction of N-heterocyclic quinazolinones: to this purpose, zinc, 41 titanium, 42 and rare-earth metal-based complexes 43 were recently developed to catalyse tandem hydroamination of amino acid esters with carbodiimides.…”