Gold Catalysis Opens Up a New Route for the Synthesis of Benzimidazoylquinoxaline Derivatives from Biomass‐Derived Products (Glycerol)

Abstract

The reaction of unsubstitued camphanyl‐piperazine 4 with ZnCl2, phenylacetylene, and benzaldehyde in toluene gave the corresponding dipropargylamine (i.e., 15) with opposite configurations at the newly formed stereogenic centres, which, upon reaction with ZnI2 resulted in the formation of a racemic mixture of 1,3‐diphenyl allene in 45 % yield. N‐Methylcamphanyl‐piperazine regioisomer 5, prepared by selective N‐methylation of the NH moiety attached to the stereogenic centre with (S)‐configuration, upon reaction with ZnCl2, phenylacetylene, and benzaldehyde in toluene, gave the corresponding propargylamine in 90 % yield, with an (S)‐configuration at the newly formed stereogenic centre, and upon subsequent reaction with ZnI2, this intermediate gave (R)‐1,3‐diphenyl allene in 52 % yield and with 96 % ee. Reaction of N‐methylcamphanyl‐piperazine isomer 5 with several 1‐alkynes and aldehydes in the presence of ZnBr2 gave the corresponding (R)‐allenes in 40–75 % yield and 79–99 % ee. In contrast, regioisomeric N‐methylcamphanyl‐piperazine 6 reacted with ZnBr2 to give the corresponding (S)‐allenes in 38–71 % yield and with 79–99 % ee. The opposite chiral discriminating abilities of the two NH moieties in camphanyl‐piperazines was confirmed by single‐crystal X‐ray analysis of the propargylamines formed. The results are discussed considering mechanisms involving the in situ formation of alkynylzinc halides, followed by diastereoselective addition to chiral iminium ion derivatives to give the corresponding propargylamines, and subsequent conversion to chiral allenes by an intramolecular 1,5‐hydrogen shift.

Cycloamination strategies for renewable N-heterocycles

“…Climent et al showed that glyceraldehyde 83 (or glycerol) undergoes oxidation-cyclization twice with o-phenylenediamine derivatives 109 to give various substituted benzimidazoylquinoxalines 115 (24-80% yields) catalyzed by ceria supported gold nanoparticles (Au/CeO 2 ) using air as the oxidant at 140°C for 24 h (Scheme 31). 254 In the reaction pathway, glyceraldehyde 83 ( possibly in situ generated from glycerol by oxidation) first proceeds coupling and cyclization with o-phenylenediamine derivatives 109 to produce the intermediate benzimidazol 114, followed by cascade oxidation-cyclization with another o-phenylenediamine 109 to afford the substituted benzimidazoylquinoxalines 115. The electron-donating substituents in the phenyl ring favor the competitive oxidative cleavage of the diol 114, and lead to a decrease in the product selectivity by formation of other azaheterocycles 116-119 (Scheme 31).…”

Recent advances in the synthesis of benzimidazol(on)es via rearrangements of quinoxalin(on)es

“…A gold catalyst (Au/CeO 2 ) was used to synthesize benzimidazolylquinoxalines by two novel methods in a multistep one-pot methodology. 80 The rst method involved the oxidative coupling of glycerol 60 with 1,2-DAB 5a performed at C using diglyme as a solvent and lead to the benzimidazolylquinoxaline compound 63a through the formation of intermediates 61a and 62a (Scheme 18). Herein, the benzimidazolylquinoxaline possesses the same substituents in both heterocycles.…”

“…hydroxymethylquinoxaline 61a, 1-(1H-benzo[d] imidazol-2-yl)ethane-1,2-diol 62a, and its protected derivative 80 were investigated (Scheme 21). 80 Following the optimization of the reaction conditions with different substrates, the results presented in Scheme 22 showed that only the reaction between glyceraldehyde and 1,2-DAB (Scheme 21, route c) in the presence of Au/CeO 2 , oxygen pressure, and at room temperature, produced the benzimidazole intermediate 62 with a high selectivity with complete conversion. Consequently, the synthesis of the benzimidazole intermediate from glyceraldehyde and 1,2-DAB derivative was chosen as the optimum rst step of the reaction.…”

“…The main product observed under these conditions is the benzimidazolylquinoxalines 63g (Scheme 22), which is formed by oxidative coupling between the intermediate 62 and the 1,2-DAB molecule 5d. 80 Both routes were applied to the synthesis of different benzimidazolylquinoxalines derivatives, obtained in yields between 60 and 80%. As can be seen from the reaction mechanism (Scheme 23) and from the data in the Scheme 20, this method cannot be used effectively in the case of the synthesis of substituted derivatives of 2-benzimidazolylquinoxalines, as the reactions of mono-substituted derivatives of 1,2-DAB proceed with the formation of the mixtures of regioisomers, which are difficult to separate.…”

Organic Synthesis Catalyzed by Supported Gold Nanoparticles

“…158 The scope of the reaction is shown in Table 12 by using a variety of different substituted amines and alcohols/aldehydes. The CeO 2 -supported gold nanoparticles prepared via deposition-precipitation method gave the moderate to good yields of benzimidazoylquinoxalines.…”