One-Pot, Three-Step Copper-Catalyzed Five-/Four-Component Reaction Constructs Polysubstituted Oxa(Thia)zolidin-2-imines

Abstract

A novel one-pot synthesis of polysubstituted oxa(thia)zolidin-2-imines has been developed. It employs A 3 -coupling of aldehyde and amine with alkyne to form propargyl amine, which on (thio)amidation with iso(thio)cyanate produces N-propargyl(thio)urea, and a cyclization reaction. A 5-exo-dig iodocyclization of N-propargylurea constructs 5-iodomethyleneoxazolidin-2-imine, while cycloisomerization of the thio analogue provides 5-methylenethiazolidin-2-imine. In this process, CuI catalysis has been found to be crucial, and the cyclization occurs through oxygen/sulfur (not nitrogen) nucleophilic attack to alkyne.The major prescription drugs contain heterocyclic scaffolds. The crucial role played by heterocycles in drug-discovery processes has long been known. 1 Recent in silico investigations on drug database toward exploration of potential 'bioactivity islands' have revealed the importance of heterocyclic scaffolds. 2 The rapid and molecular-diversity-feasible construction of new and 'privileged' heterocyclic scaffolds has gained importance. In this direction, the amalgamation of a multicomponent reaction 3,4 and a consecutive one-pot process (domino, cascade, or tandem), 5 which in many cases gains efficiency under transition-metal catalysis, 6 is a golden nugget for the rapid construction of polysubstituted molecular scaffolds with atom-, step-, and pot-economy. 7 In this approach, variation in reactants can also generate a large number of compounds. As part of our research program aimed at realizing new leads, we became interested in developing a one-pot, multicomponent reaction that could afford pharmaceutically significant heterocyclic scaffolds. We speculated that a sequence of reactions of a multicomponent condensation of aldehyde, amine, and alkyne (A 3 -coupling) to form propargyl amine, 8 which on amidation produces Npropargylurea, whose endo-or exo-dig cycloisomerization with alkyne in the terminal step could produce dihydropyrimidinone I or imidazolidinone, respectively (Scheme 1). The later scaffold via isomerization of the double bond might possibly form the aromatic compound imidazolone II. Based on known therapeutic importance of these scaffolds 9,10 and the potential efficiency of the synthetic approach, we were interested in exploring the reaction sequence. A one-pot version of this synthesis, which was our endeavor also, is more challenging, because the process requires the catalyst and conditions compatibility and considerably high conversion in each reaction step. Coinage metal (Cu, Ag, or Au) catalyst could be crucial for A 3 -coupling and the cycloisomerization with electrophilic activation of alkyne. 11 Cu(I) halide as catalyst was preferentially chosen because of its known

Electrochemical Selenylation‐Induced Annulation of Alkenyl Ureas to Access Cyclic Isoureas

“…On the basis of the above‐mentioned results and the previous reported, [4–8,13] a possible mechanism for this reactions is proposed, as depicted in Figure 3. Initially, a selenonium cation A is formed from the anodic oxidation of the diselenide 2 a .…”

“…reported the in‐situ generation of urine derivatives from amines and isocyanates, following by cycloaddition to form cyclic isoureas (Scheme 1a) [4a] . In 2012, Guchhait's group developed a powerful multicomponent reaction for the synthesis of iodinated cyclic isoureas in one‐pot (Scheme 1b) [5] . In addition, several catalytic system had developed for cyclic isoureas by the employment of transition metal catalyst, such as Pd, [6a–c] Ag, [6c–e] Au, [6d–e] and Cu [6f–h] (Scheme 1c).…”

“…[4a] In 2012, Guchhait's group developed a powerful multicomponent reaction for the synthesis of iodinated cyclic isoureas in one-pot (Scheme 1b). [5] In addition, several catalytic system had developed for cyclic isoureas by the employment of transition metal catalyst, such as Pd, [6a-c] Ag, [6c-e] Au, [6d-e] and Cu [6f-h] (Scheme 1c). Moreover, Shibata's group reported the Bu 2 SnI 2 À InCl 3 catalyzed annulation of epoxides and diphenyl carbodiimide to afford cyclic isoureas (Scheme 1d), [7] and Cariou's group reported an iodine(III)-mediated for the synthesis of cyclic isoureas through cationic cyclizations of unsaturated N-alkoxyureas (Scheme 1e).…”

Copper-Catalyzed One-Pot Synthesis of Thiazolidin-2-imines

“…Along these lines, several transformations toward thiazolidin-2-imines have been reported in the literature. Guchhait and co-workers have reported an efficient and sustainable protocol for the synthesis of thiazolidin-2-imines via a one-pot, two-step procedure, employing as starting materials primary amines and aldehydes, or preformed imines, along with terminal alkynes and isothiocyanate derivatives, in moderate yields (Scheme A) . This was the first reported protocol for the synthesis of thiazolidin-2-imines via a one-pot, multicomponent approach, without isolating the required propargylamine intermediates.…”

Highly efficient fixation of carbon dioxide into 2-oxazolidinones under mild conditions by using a reusable ionic liquid/CuI catalyst system

“…However, most protocols for synthesizing 2-oxazolidinones require harsh conditions, including high pressure of CO 2 and high temperature, long reaction times, and use of hazardous and expensive catalysts or solvents, and give poor yields. [26][27][28] Prof. Li's group was the first to investigate the four-component one-pot synthesis in the aqueous medium, with a moderate yield of 2-oxazolidinone of 62%. 29 In our previous study, we showed another approach involving the addition of 4 Å molecular sieves (MSs) to improve CO 2 capture and facilitate carboxylation.…”