Clean Synthesis of <i>N</i>-Pyrrolyl Azoles by Metal-Free Oxidative Cross-Coupling Using Recyclable Hypervalent Iodine Reagent

Abstract

The facile and clean oxidative coupling reaction of pyrroles with azoles has been achieved using the recyclable hypervalent iodine(III) reagents having adamantane structures. These iodine(III) reagents could be recovered from the reaction mixtures by a simple solid-liquid separation, i.e., filtration, for reuse.Key words oxidative coupling; hypervalent iodine reagent; recycle; pyrrole; azole; C-N bond formationThe N-pyrrolyl azoles are important fragments in the molecules of biological systems or in many pharmaceuticals, insecticides, and functional materials, especially, fluorescent dyes. [1][2][3][4] In spite of this interest, the preparations of N-aryl azoles are severely restricted because the nitrogen heteroaromatics are sometimes not a good substrate to use in the traditional arylation methods such as the Ullmann coupling, [5][6][7][8][9][10][11] since the pyrrole-based metal and halide compounds are sometimes unstable. Katritzky et al. reported the synthesis of pyrrolyl-benzotriazoles by the Mannich condensation of o-phthalaldehyde and 2,5-dimethoxy-2,5-dihydrofuran with primary amines, 12) but this method was not effective for pyrroles, and the desired products were produced only in less than 10% yields. As a new approach, the oxidative C-H bond functionalization strategies of pyrroles [13][14][15][16][17][18][19][20][21][22] might be expected to be an attractive methodology for enabling rapid access to these molecules. Recently, we have developed a new hypervalent iodine-induced oxidative coupling of pyrroles at the N 1 -positions of the azoles. 23) In 2014, Chen and colleagues reported the oxidative coupling method of 1,2,3-triazoles with pyrroles using N-iodosuccinimide (NIS) as an oxidant, in which the reactions preferentially occurred at the N 2 -position of the 1,2,3-triazoles.24) However, these methods produced stoichiometric quantities of iodoarene or succinimide as a waste product after the reaction (Chart 1).Hypervalent iodine reagents have received much attention due to their mild oxidation abilities and low toxicity, easy handling, as alternatives to toxic heavy metal reagents. [25][26][27][28][29][30][31][32] For developing a new coupling for heteroaromatic compounds, we have been engaged in the study of the oxidative C-H bond arylations using hypervalent iodine reagents that utilize the new reactivities of the heteroaromatic iodonium intermediates. [33][34][35][36][37] As mentioned, we developed a hypervalent iodineinduced oxidative coupling of pyrroles at the N 1 -positions of the azoles.23) This new method is versatile in allowing the reactions under metal-free and mild conditions, and tolerates a diverse series of functionalities of the pyrroles and azole coupling partners. We envisioned that a recycling version of this oxidative coupling should become feasible and provide an eco-friendly synthetic method (Chart 2) because a number of recent studies have demonstrated the utility of the recyclable hypervalent iodine reagents. 38-40) Results and DiscussionThe use of recyclable hypervalent ...

Metal-Free Oxidative Cross-Coupling Reaction of Heteroaromatic and Related Compounds

“…As a result, when TMSBr was used in combination with PIDA, the best results were obtained in forming N-pyrrolylazole, and the C-N-coupling reaction proceeded in good yield. 107,108) The scope of the substrate for our method proceeded without being affected by the N-substituent, and products 5 were obtained in good yield (Chart 13). N-Free pyrrole and 2-ethyl Chart 16.…”

Recyclable Hypervalent Iodine Reagents in Modern Organic Synthesis

“…Catalysts 61 and 73 can be readily separated from reaction mixtures by filtration and reused several times without any significant loss in catalytic activity. 52 In 2018, Wei et al developed inorganic ligand-coordinated polyoxametallate (POM) iodine catalyst 76 by treating ammonium heptamolybdate (75) with orthoperiodic acid (74) in an aqueous medium at 95 °C for 3 hours (Scheme 14). 53 This catalyst selectively oxidizes various alcohols, including primary, secondary, allylic, and benzylic, under aerobic conditions without the use of toxic oxidants such as Oxone ® , or sensitive organic ligands.…”

“…73 In 2015, Kita and co-workers achieved the cross-coupling of pyrroles 128 and azoles 129 to afford coupling product 130 in 52-78% yield using 1,3,5,7-tetrakis [4-(diacetoxyiodo)phenyl]adamantane (80) in combination with bromotrimethylsilane at 70 °C (Scheme 21). 74 In 2018, Kita et al reported the cross-coupling reaction of pyrroles 131 with the electron-rich arene 132 using adamantane-core-based reagent 80 in hexafluoroisopropanol (HFIP) at room temperature (Scheme 22). 75 Scheme 22 Metal-free oxidative cross-coupling of pyrroles 131 with 132 using reagent 80…”

Metal-Free Oxidative Cross-Coupling of Pyrroles with Electron-Rich Arenes Using Recyclable Hypervalent Iodine(III) Reagent

“…Utilizing the reaction of N-methylpyrrole 3b, the C2-arylation developed in this study first gave coupling product 5b in 61% yield. Subsequently, under the conditions we have previously developed, 12 the second N-arylation introduced the 1,2,3-triazole 6a and 1,2,3-benzotriazole 6b moieties took place and the diarylated products 7a and 7b were obtained (Scheme 3). Nitrogen heterocycles are known as core of various natural products and functional materials, among which azoles and pyrroles have the most frequent occurrence.…”