Copper‐Catalyzed Cascade Cyclization Reactions of Isocyanides with α‐Diazocarbonyls as N‐Terminal Electrophiles: Efficient Synthesis of 2‐Imidazolines and 1,1′‐Biimidazoles

Abstract

The reactions of α‐diazocarbonyls have been extensively studied and widely applied in organic synthesis acting as 1,3‐dipoles, metal carbene precursors and C‐nucleophiles. However, the utility of the electrophilic capability of their terminal nitrogen has been a challenging problem. Herein, a novel copper‐catalyzed cascade cyclization reaction of isocyanides with α‐diazocarbonyls as N‐terminal electrophiles has been developed for the first time. The reaction involves a sequential intermolecular nucleophilic addition/[3+2] cycloaddition/intramolecular cyclization‐ring‐opening/elimination procedure and provides a new and efficient method for the construction of imidazolines and biimidazoles in a single step from readily available starting materials under very mild conditions.magnified image

Recent Advances in the Synthesis of Imidazolines (2009–2020)

“…A mild dehydrating agent, trimethylsilyl polyphosphate (PPSE) mediated N-substituted 2-imidazoline (63) synthesis was developed by Salerno and coworkers (Scheme 18). [38] N-monosubstituted ethylenediamine (61), and aliphatic acyl chloride was used as starting material to form intermediate amide (62). Finally, cyclocondensation of the intermediate 62 generates the desired imidazoline.…”

“…Zhao and co-workers developed a copper-catalyzed cascade reaction of α-diazocarbonyls (183) with isocyanide (184) to synthesize 2-imidazolines (Scheme 53). [62] The initial optimizations were performed by reacting ethyl diazoacetate (R 1 = H, R 2 = OEt) (183) with ethyl isocyanoacetate (184), in the presence of a catalyst (CuI, CuBr, Ag 2 CO 3 , Cu(OTf) 3 , FeCl 3 ) and a base (Cs 2 CO 3 , t BuOK, K 2 CO 3 , DBU). No product formation was observed in the reaction mediated by Cu(OTf) 3 or FeCl 3 along with a base.…”

Diazocarbonyl and Related Compounds in the Synthesis of Azoles

“…In 2017, Zhao and co-workers devised an effective copper-catalyzed cascade cyclization reaction of isocyanides 157 with α -diazocarbonyls 158 [ 77 ]. This protocol furnishes imidazolines 159 ( Scheme 36 , a) and biimidazoles 160 ( Scheme 36 b) in good yields under very mild conditions.…”

Environmentally benign and diastereoselective synthesis of 2,4,5-trisubstituted-2-imidazolines

“…2 Imidazolines and imidazolinium ions have been used as surfactants, 3 ionic liquids, 4 ionic polymers, 5 and in the eld of coordination chemistry and catalysis. [6][7][8][9][10] Among the 2-imidazoline derivatives, 2,4,5-triaryl imidazolines (also called amarines) have been gaining increased interest because their hydrolysis provides 1,2-diaryl-1,2-diaminoethanes featuring a C 2 -symmetric structure, important in catalysis. [11][12][13] The reported syntheses for obtaining 2,4,5-trisubstituted-2imidazolines are summarised in Table 1.…”