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Rhodium-Catalyzed Synthesis of Unsymmetric Di(heteroaryl) Ethers Using Heteroaryl Exchange Reaction

Abstract

Unsymmetric di(heteroaryl) ethers were synthesized by the rhodium-catalyzed heteroaryl exchange reaction of heteroaryl aryl ethers and heteroaryl esters at equilibrium. Diverse unsymmetric di(heteroaryl) ethers containing five- and six-membered heteroarenes were obtained. Di(heteroaryl) ethers can be synthesized starting from diaryl ethers, because heteroaryl aryl ethers are obtained by the heteroaryl exchange reaction of diaryl ethers.

Diaryl ethers are widely present in natural products and functional materials, and substitution of the aryl groups with heteroarenes is an attractive method to modify their properties such as conformation, electron density, and lipophilicity.[1] However, known unsymmetrical di(heteroaryl) ethers, where two aryl groups in the diaryl ether are substituted by different heteroarenes, are limited.[2] Several di(pyridyl) ethers have been synthesized by the classical nucleophilic aromatic substitution of halopyridines and hydroxypyridines in the presence of stoichiometric amounts of bases,[3] which in some cases employ metal catalysis.[4] Di(pyridyl) ethers have been synthesized by the reaction of hydroxypyridine and pyridine-N-oxides.[5] These aromatic substitution reactions in most cases provide di(pyridyl) ethers. The palladium-catalyzed substitution reaction of 2-pyrimidyl or 4-quinazolyl derivatives with the pyridotriazol-1-yloxy leaving group and heteroarylboric acids has been reported. It is noted that the heteroarylboric acids are converted into hydroxyheteroarenes by palladium-catalyzed oxidation, which nucleophilically substitute the pyridotriazol-1-yloxy group.[6] The reaction, however, is restricted to 2-pyrimidyl or 4-quinazolyl derivatives, and the use of hydroxyheteroarenes instead of heteroarylboric acids is preferable because of their availability. It should also be noted that all these substitution reactions employ stoichiometric amounts of bases.

Recently, we have reported the rhodium-catalyzed synthesis of di(heteroaryl) sulfides and di(heteroaryl)methanes from heteroaryl ethers by heteroaryl exchange reaction.[7a] [b] The synthesis provided di(heteroaryl) compounds connected by a one-atom of sulfur and carbon, using the C–O bond cleavage of heteroaryl aryl ethers. It was then considered that various di(heteroaryl) ethers could be obtained from heteroaryl ethers by a heteroaryl exchange reaction, although such a method had not yet been developed.

Described here is the rhodium-catalyzed synthesis of unsymmetric di(heteroaryl) ethers by heteroaryl exchange (Scheme [1], B). Under rhodium-catalyzed conditions, the reaction of heteroaryl aryl ethers and heteroaryl benzoates provided di(heteroaryl) ethers. The C–O bond cleavage and heteroaryl exchange of heteroaryl aryl ethers provided unsymmetric di(heteroaryl) ethers containing multiple heteroatoms. The advantages of this method are as follows: 1) diverse unsymmetrical di(heteroaryl) ethers containing various five- and six-membered heteroarenes can be synthesized; 2) substrates are stable and readily available; 3) the rhodium-catalyzed reaction does not employ metal bases. It should also be noted that unsymmetric di(heteroaryl) ethers can, in principle, be synthesized from diaryl ethers by subsequent rhodium-catalyzed heteroaryl exchange reactions (Schemes 1, A and B).

It was initially confirmed that the HetAr–O bonds of heteroaryl aryl ethers can be cleaved and exchanged by rhodium catalysis. When 2-(4-chlorophenoxy)-6-chlorobenzoxazole (1) was reacted with 2-phenoxybenzothiazole (2a, 3 equiv) in the presence of RhH(PPh₃)₄ (5 mol%) and dppBz (10 mol%, dppBz = 1,2-bis(diphenylphosphino)benzene) in refluxing chlorobenzene for five hours, 2-phenoxy-6-chlorobenzoxazole (3a, 72%), and 2-(4-chlorophenoxy)benzothiazole (4, 62%) were obtained with recovery of 1 (18%) and 2a (74%, Scheme [2]). No reaction occurred in the absence of the RhH(PPh₃)₄ or dppBz. The use of several bidentate ligands revealed a high efficiency of dppBz for this reaction: 1,2-bis(diphenylphosphino)ethane (yields of 3a and 4: 52% and 79%), cis-1,2-bis(diphenylphosphino)ethylene (59% and 78%), 1,3-bis(diphenylphosphino)propane (15% and 29%), and 1,4-bis(diphenylphosphino)butane (not detected). Monodentate ligands tris(4-methoxyphenyl)phosphine and tris(4-chlorophenyl)phosphine were ineffective. These results show that the bidentate phosphine ligands with phosphino groups separated by two carbon atoms are essential. Previously, we reported that the HetAr–O bond was selectively cleaved over the Ar–O bond in the rhodium-catalyzed fluorination, sulfidation, and methylation reactions of heteroaryl aryl ethers (HetAr–O–Ar).[7a] [b] [c] It was then considered that the 1,3-benzoxazolyl–O bonds of 1 and 2a were selectively cleaved and exchanged. When the molar ratio 2a/1 was changed from 3 to 1, the yields of 3a and 4 decreased to 46% and 48%, respectively. The reverse reaction of 3a and 4 under the same reaction conditions gave 1 and 2a in 41% and 45% yields, respectively, which naturally indicated the equilibrium nature of the reaction. Electron-donating and electron-withdrawing groups at the aryl 4-substituents exerted a small effect. The rhodium catalyst can cleave the HetAr–O bond without using the added bases and exchanged the heteroaryl groups.

The heteroaryl aryl ethers, which are the substrates in the reactions in Scheme [2], can be synthesized from activated diaryl ethers (Scheme [3]).[8] Heteroaryl aryl ethers containing five- and six-membered heteroarenes 7a–d were synthesized from 4-(4-chlorophenoxy)-3-trifluoromethylbenzonitrile (5) under rhodium-catalyzed conditions. The rhodium complex catalyzes the aryl–O bond cleavage and heteroaryl exchange of the activated diaryl ether as well as the heteroaryl aryl ethers.

The heteroaryl aryl ethers are obtained by the heteroaryl exchange of diaryl ethers via HetAr–OAr bond cleavage (Scheme [4], blue line, reaction mode I). It was noted, however, that the di(heteroaryl) ethers cannot be obtained by this method because the HetAr–OAr bond is preferentially cleaved, and it is necessary to transfer the heteroaryloxy group with HetArO–C bond cleavage. It was considered that the unsymmetric di(heteroaryl) ethers could be formed using heteroaryl esters, in which HetArO–COPh bond cleavage occurred because this bond is likely weaker than the HetAr–O bond (red line, reaction mode II).

The use of heteroaryl benzoate, as expected, formed unsymmetric di(heteroaryl) ethers from heteroaryl (4-chlorophenyl) ethers. When 2-phenoxybenzothiazole (2a, 3 equiv) was reacted with pyridine-3-yl benzoate (9) in the presence of RhH(PPh₃)₄ (5 mol%) and dppBz (10 mol%) in refluxing chlorobenzene for five hours, 2-(3-pyridinyl­oxy)benzothiazole (10, 69%) and phenyl benzoate (11, 70%) were obtained with recovery of 2a (73%) and 9 (25%, Scheme [5]).[9] No reaction occurred in the absence of RhH(PPh₃)₄ or dppBz. When the molar ratio 2a/9 was changed from 3 to 1, the yields of 10 and 11 decreased to 37% and 39%, respectively. The reverse reaction of 10 and 11 under the same reaction conditions gave 2a and 9 in 39% and 40% yields, respectively, which indicated the equilibrium nature of the reaction. The heteroaryloxy group of heteroaryl benzoate was transferred to the heteroaryl aryl ethers by rhodium catalysis via HetArO–COPh bond cleavage.

Various unsymmetric di(heteroaryl) ethers were synthesized by the heteroaryl exchange reaction of heteroaryl aryl ethers and heteroaryl benzoates (Table [1]). The heteroaryl 4-chlorophenyl ethers containing five-membered heteroarenes such as 1,3-benzothiazolyl, 1,3-benzoxazolyl, 1,3-oxazolyl, 2-furyl, and 2-thienyl groups reacted with pyridine-3-yl benzoate (9), and the corresponding heteroaryl 3-pyridyl ethers 10, 14a–k were obtained. The six-membered heteroaryl 4-chlorophenyl ethers with 2-triazyl, 4-quinazolinyl, and 3-quinolinyl groups were also converted into the di(heteroaryl) ethers 14l–o. The reaction of 3-quinolinyl, 5-quinolinyl, and 8-quinolinyl benzoates with 2-(4-chlorophenoxy)benzothiazole gave the corresponding benzothiazolyl quinolinyl ethers 14p–r in good yield. Note that the use of 4-pyridyl and 2-pyridyl benzoate derivatives formed unsymmetric benzothiazolyl 2- and 4-pyridyl ethers 14s–u without isomerization to N-heteroaryl pyridones.[10] The structure of 14u was confirmed by X-ray crystal structure analysis (Figure [1]).[11] The unsymmetric five-membered di(heteroaryl) ethers containing furyl and thienyl groups 14v–y were also obtained. The resulting unsymmetric di(heteroaryl) ethers are new compounds, except for 14l. This reaction is a novel catalytic method for synthesizing diverse unsymmetric di(heteroaryl) ethers from heteroaryl aryl ethers and heteroaryl benzoates, which are stable and readily available.

The reaction of diaryl ethers and a heteroaryl ester was also examined. The reaction of 4-(4-chlorophenoxy)-3-trifluoromethylbenzonitrile (5a) and pyridine-3-yl benzoate (9) gave 3-trifluoromethyl-4-(3-pyridinyloxy)benzonitrile (16a) and 15 in 72% and 69% yields, respectively (Scheme [6]). 1-Chloro-4-(4-nitrophenoxy)benzene also reacted. The heteroaryl aryl ethers can be obtained from diaryl ethers and heteroaryl esters.

A possible mechanism of the reaction is shown in Scheme [7]. The phosphine ligand in RhH(PPh₃)₄ is exchanged with dppBz, and the oxidative addition of O-(heteroaryl) ester provides the benzoylrhodium intermediate A. The intermediate A then undergoes a heteroaryl exchange reaction with heteroaryl aryl ether forming HetAr′–Rh(III)–OHetAr complex B and benzoate ester, and the unsymmetrical di(heteroaryl) ethers are liberated by reductive elimination with the regeneration of the rhodium catalyst. In this reaction, the HetAr–O bond in the ethers and HetArO–COPh bond in the esters are regioselectively cleaved, and the other C–O bond does not react. It is considered that the heteroaryl groups and aryl groups with electron-withdrawing substituent weaken the C–O bond.[7c] [12]

Table 1 Rhodium-Catalyzed Synthesis of Unsymmetric Di(heteroaryl) Ethers.

14a R = MeO, R′ = X = H, 60% 14b R = R′ = MeO, X = H, 64% 14c R = R′ = H, X = Cl, 21%	14d R = H, 47% 14e R = Cl, 70% 14f R = Me, 53%	14g R = Ph, 75% 14h R = H, 52%
14i R = CN, 58% 14j R = MeCO, 73%	14k R = PhCO, 50%	14l 54%b
14m R = H, 68% 14n R = MeO, 78%	14o 72%b	14p 69%
14q 66%	14r 63%	14s 75%
14t R = Ph, 77% 14u R = Cl, 6%, 23%c	14v R = MeCO, 72% 14w R = CN, 52%	14x R = Me, X = O, 49% 14y R = Ph, X = S, 43%

^a The C–O bonds formed by the reaction are shown in red.

^b 12 (1 equiv) and 13 (3 equiv) were reacted.

^c RhH(PPh₃)₄ (20 mol%) and dppBz (40 mol%) were used.

In summary, unsymmetric di(heteroaryl) ethers were synthesized from heteroaryl aryl ethers and heteroaryl benzoates by a heteroaryl exchange reaction. Diverse unsymmetric di(heteroaryl) ethers containing five- and six-membered heteroarenes were obtained in high yields. Di(heteroaryl) ethers can be synthesized starting from activated diaryl ethers using the rhodium-catalyzed heteroaryl exchanged reaction.

Acknowledgment

This research was supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Japan Agency for Medical Research and Development (AMED) and JSPS KAKENHI Grant Number JP15H00911.

• References and Notes

• 1 Tynebor RM. Chen M.-H. Natarajan SR. O’Neill EA. Thompson JE. Fitzgerald CE. O’Keefe SJ. Doherty JB. Bioorg. Med. Chem. Lett. 2011; 21: 411
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• 2a AMG 458: Liu L. Siegmund A. Xi N. Kaplan-Lefko P. Rex K. Chen A. Lin J. Moriguchi J. Berry L. Huang L. Teffera Y. Yang Y. Zhang Y. Bellon SF. Lee M. Shimanovich R. Bak A. Dominguez C. Norman MH. Harmange J.-C. Dussault I. Kim T.-S. J. Med. Chem. 2008; 51: 3688
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• 2b Peace S. Philp J. Brooks C. Piercy V. Moores K. Smethurst C. Watson S. Gaines S. Zippoli M. Mookherjee C. Ife R. Bioorg. Med. Chem. Lett. 2010; 20: 3961
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• 3a Che YL. Braselton J. Forman J. Gallaschun RJ. Mansbach R. Schmidt AW. Seeger TF. Sprouse JS. Tingley III FD. Winston E. Schulz DW. J. Med. Chem. 2008; 51: 1377
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• 3b Voisin AS. Bouillon A. Lancelot J.-C. Lesnard A. Rault S. Tetrahedron 2006; 62: 6000
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Exceptionally, substitution reaction of 2,5-dinitrofuran and 3-hydroxypyridine was reported:
• 3c Gavade S. Padiya K. Bajare S. Balaskar R. Mane D. J. Heterocycl. Chem. 2011; 48: 458
  CrossrefSearch in Google Scholar

Reaction of 2-chloro-1,3-oxazolyl compound and 3-hydroxypyridine:
• 3d Oka Y. Yabuuchi T. Fujii Y. Ohtake H. Wakahara S. Matsumoto K. Endo M. Tamura Y. Sekiguchi Y. Bioorg. Med. Chem. Lett. 2012; 22: 7534
  CrossrefSearch in Google Scholar

Copper-catalyzed reaction:
• 4a Reddy KU. M. Kumar KS. Reddy AP. Asian J. Chem. 2014; 26: 4747
  Search in Google Scholar
• 4b Maiti D. Buchwald SL. J. Org. Chem. 2010; 75: 1791
  CrossrefSearch in Google Scholar
• 4c Altman RA. Buchwald SL. Org. Lett. 2007; 9: 643
  CrossrefSearch in Google Scholar
• 4d Barker DJ. Summers LA. J. Heterocycl. Chem. 1983; 20: 1411
  CrossrefSearch in Google Scholar

Reaction of 2-bromopyridine and water:
• 4e Tlili A. Monnier F. Taillefer M. Chem. Eur. J. 2010; 16: 12299
  CrossrefPubMedSearch in Google Scholar

Cobalt-catalyzed reaction:
• 4f Kundu D. Tripathy M. Maity P. Ranu BC. Chem. Eur. J. 2015; 21: 8727
  CrossrefPubMedSearch in Google Scholar

Palladium-catalyzed reaction:
• 4g Zhang T. Tudge MT. Tetrahedron Lett. 2015; 56: 2329
  CrossrefSearch in Google Scholar
• 4h Platon M. Cui L. Mom S. Richard P. Saeys M. Hierso J.-C. Adv. Synth. Catal. 2011; 353: 3403
  CrossrefSearch in Google Scholar
• 5a Rodrigues N. Boiaryna L. Vercouillie J. Guilloteau D. Suzenet F. Buron F. Routier S. Eur. J. Org. Chem. 2016; 5024
• 5b Londregan AT. Jennings S. Wei L. Org. Lett. 2011; 13: 1840
  CrossrefSearch in Google Scholar
• 6a Wacharasindhu S. Bardhan S. Wan Z.-K. Tabei K. Mansour TS. J. Am. Chem. Soc. 2009; 131: 4174
  CrossrefSearch in Google Scholar
• 6b Bardhan S. Wacharasindhu S. Wan Z.-K. Mansour TS. Org. Lett. 2009; 11: 2511
  CrossrefPubMedSearch in Google Scholar
• 6c Bardhan S. Tabei K. Wan Z.-K. Mansour TS. Tetrahedron Lett. 2009; 50: 5733
  CrossrefSearch in Google Scholar
• 7a Arisawa M. Tazawa T. Tanii S. Horiuchi K. Yamaguchi M. J. Org. Chem. 2017; 82: 804
  CrossrefPubMedSearch in Google Scholar
• 7b Li G. Arisawa M. Yamaguchi M. Chem. Commun. 2014; 50: 4328
  CrossrefPubMedSearch in Google Scholar
• 7c Arisawa M. Tanii S. Tazawa T. Yamaguchi M. Chem. Commun. 2016; 52: 11390
  CrossrefPubMedSearch in Google Scholar

It was reported that diphenyl ether can be synthesized by dehydration of phenol, and heteroaryl aryl ethers and di(heteroaryl) ethers can, in principle, be obtained from phenols without using a base:
• 8a Zsolczai D. Németh J. Hell Z. Tetrahedron Lett. 2015; 56: 6389
  CrossrefSearch in Google Scholar
• 8b Buske GR. Garces JM. Dianis WP. US 5288922, 1994
• 8c Karuppannasamy S. Narayanan K. Pillai CN. J. Catal. 1980; 66: 281
  CrossrefSearch in Google Scholar
• 9 General Procedure for the Synthesis of Unsymmetric Di(heteroaryl) Ethers In a two-necked flask equipped with a magnetic stirrer bar and a reflux condenser were placed RhH(PPh₃)₄ (5 mol%, 14.4 mg), dppBz (10 mol%, 11.1 mg), 2-phenoxy-1,3-benzothiazole (2a, 0.75 mmol, 170.5 mg), and pyridine-3-yl benzoate (9, 0.25 mmol, 49.8 mg) in chlorobenzene (0.5 mL) under an argon atmosphere, and the solution was stirred and heated at reflux for 5 h. The solvent was removed under reduced pressure, and the residue was purified by flush column chromatography on silica gel giving 2-(3-pyridinyloxy)-1,3-benzothiazole (10, 69%, 39.4 mg) and phenylbenzoate (11, 70%, 34.7 mg) with recovery of 2a (73%, 124.4 mg) and 9 (25%, 12.5 mg). Analytical Data of Compound 10 Colorless solid; mp 63.0–64.0 °C (hexane). ¹H NMR (400 MHz, CDCl₃): δ = 7.31 (1 H, td, J = 1.2, 8.0 Hz), 7.41 (2 H, t, J = 8.0 Hz), 7.72 (2 H, m), 7.82 (1 H, ddd, J = 1.6, 3.2, 8.4 Hz), 8.56 (1 H, dd, J = 1.2, 4.8 Hz), 8.73 (1 H, d, J = 2.8 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 121.4, 121.9, 124.2, 124.5, 126.4, 128.0, 132.3, 142.7, 147.0, 148.7, 151.2, 170.8. IR (KBr) 3060, 1527, 1475, 1440, 1428, 1256, 1235, 1021 cm^–1. MS (EI): m/z (%) = 228 (100) [M⁺], 200 (50) [M⁺ – CN]. HRMS: m/z calcd for C₁₂H₈N₂OS: 228.0357; found: 228.0343.
• 10 You F. Twieg RJ. Tetrahedron Lett. 1999; 40: 8759
  CrossrefSearch in Google Scholar
• 11 Crystallographic data including structure factors have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1534272 for compound 14u. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 12 For a related observation see: Sawatlon B. Wititsuwannakul T. Tantirungrotechai Y. Surawatanawong P. Dalton Trans. 2014; 43: 18123
  CrossrefPubMedSearch in Google Scholar

• References and Notes

• 1 Tynebor RM. Chen M.-H. Natarajan SR. O’Neill EA. Thompson JE. Fitzgerald CE. O’Keefe SJ. Doherty JB. Bioorg. Med. Chem. Lett. 2011; 21: 411
  CrossrefSearch in Google Scholar
• 2a AMG 458: Liu L. Siegmund A. Xi N. Kaplan-Lefko P. Rex K. Chen A. Lin J. Moriguchi J. Berry L. Huang L. Teffera Y. Yang Y. Zhang Y. Bellon SF. Lee M. Shimanovich R. Bak A. Dominguez C. Norman MH. Harmange J.-C. Dussault I. Kim T.-S. J. Med. Chem. 2008; 51: 3688
  CrossrefPubMedSearch in Google Scholar
• 2b Peace S. Philp J. Brooks C. Piercy V. Moores K. Smethurst C. Watson S. Gaines S. Zippoli M. Mookherjee C. Ife R. Bioorg. Med. Chem. Lett. 2010; 20: 3961
  CrossrefSearch in Google Scholar
• 3a Che YL. Braselton J. Forman J. Gallaschun RJ. Mansbach R. Schmidt AW. Seeger TF. Sprouse JS. Tingley III FD. Winston E. Schulz DW. J. Med. Chem. 2008; 51: 1377
  CrossrefPubMedSearch in Google Scholar
• 3b Voisin AS. Bouillon A. Lancelot J.-C. Lesnard A. Rault S. Tetrahedron 2006; 62: 6000
  CrossrefSearch in Google Scholar

Exceptionally, substitution reaction of 2,5-dinitrofuran and 3-hydroxypyridine was reported:
• 3c Gavade S. Padiya K. Bajare S. Balaskar R. Mane D. J. Heterocycl. Chem. 2011; 48: 458
  CrossrefSearch in Google Scholar

Reaction of 2-chloro-1,3-oxazolyl compound and 3-hydroxypyridine:
• 3d Oka Y. Yabuuchi T. Fujii Y. Ohtake H. Wakahara S. Matsumoto K. Endo M. Tamura Y. Sekiguchi Y. Bioorg. Med. Chem. Lett. 2012; 22: 7534
  CrossrefSearch in Google Scholar

Copper-catalyzed reaction:
• 4a Reddy KU. M. Kumar KS. Reddy AP. Asian J. Chem. 2014; 26: 4747
  Search in Google Scholar
• 4b Maiti D. Buchwald SL. J. Org. Chem. 2010; 75: 1791
  CrossrefSearch in Google Scholar
• 4c Altman RA. Buchwald SL. Org. Lett. 2007; 9: 643
  CrossrefSearch in Google Scholar
• 4d Barker DJ. Summers LA. J. Heterocycl. Chem. 1983; 20: 1411
  CrossrefSearch in Google Scholar

Reaction of 2-bromopyridine and water:
• 4e Tlili A. Monnier F. Taillefer M. Chem. Eur. J. 2010; 16: 12299
  CrossrefPubMedSearch in Google Scholar

Cobalt-catalyzed reaction:
• 4f Kundu D. Tripathy M. Maity P. Ranu BC. Chem. Eur. J. 2015; 21: 8727
  CrossrefPubMedSearch in Google Scholar

Palladium-catalyzed reaction:
• 4g Zhang T. Tudge MT. Tetrahedron Lett. 2015; 56: 2329
  CrossrefSearch in Google Scholar
• 4h Platon M. Cui L. Mom S. Richard P. Saeys M. Hierso J.-C. Adv. Synth. Catal. 2011; 353: 3403
  CrossrefSearch in Google Scholar
• 5a Rodrigues N. Boiaryna L. Vercouillie J. Guilloteau D. Suzenet F. Buron F. Routier S. Eur. J. Org. Chem. 2016; 5024
• 5b Londregan AT. Jennings S. Wei L. Org. Lett. 2011; 13: 1840
  CrossrefSearch in Google Scholar
• 6a Wacharasindhu S. Bardhan S. Wan Z.-K. Tabei K. Mansour TS. J. Am. Chem. Soc. 2009; 131: 4174
  CrossrefSearch in Google Scholar
• 6b Bardhan S. Wacharasindhu S. Wan Z.-K. Mansour TS. Org. Lett. 2009; 11: 2511
  CrossrefPubMedSearch in Google Scholar
• 6c Bardhan S. Tabei K. Wan Z.-K. Mansour TS. Tetrahedron Lett. 2009; 50: 5733
  CrossrefSearch in Google Scholar
• 7a Arisawa M. Tazawa T. Tanii S. Horiuchi K. Yamaguchi M. J. Org. Chem. 2017; 82: 804
  CrossrefPubMedSearch in Google Scholar
• 7b Li G. Arisawa M. Yamaguchi M. Chem. Commun. 2014; 50: 4328
  CrossrefPubMedSearch in Google Scholar
• 7c Arisawa M. Tanii S. Tazawa T. Yamaguchi M. Chem. Commun. 2016; 52: 11390
  CrossrefPubMedSearch in Google Scholar

It was reported that diphenyl ether can be synthesized by dehydration of phenol, and heteroaryl aryl ethers and di(heteroaryl) ethers can, in principle, be obtained from phenols without using a base:
• 8a Zsolczai D. Németh J. Hell Z. Tetrahedron Lett. 2015; 56: 6389
  CrossrefSearch in Google Scholar
• 8b Buske GR. Garces JM. Dianis WP. US 5288922, 1994
• 8c Karuppannasamy S. Narayanan K. Pillai CN. J. Catal. 1980; 66: 281
  CrossrefSearch in Google Scholar
• 9 General Procedure for the Synthesis of Unsymmetric Di(heteroaryl) Ethers In a two-necked flask equipped with a magnetic stirrer bar and a reflux condenser were placed RhH(PPh₃)₄ (5 mol%, 14.4 mg), dppBz (10 mol%, 11.1 mg), 2-phenoxy-1,3-benzothiazole (2a, 0.75 mmol, 170.5 mg), and pyridine-3-yl benzoate (9, 0.25 mmol, 49.8 mg) in chlorobenzene (0.5 mL) under an argon atmosphere, and the solution was stirred and heated at reflux for 5 h. The solvent was removed under reduced pressure, and the residue was purified by flush column chromatography on silica gel giving 2-(3-pyridinyloxy)-1,3-benzothiazole (10, 69%, 39.4 mg) and phenylbenzoate (11, 70%, 34.7 mg) with recovery of 2a (73%, 124.4 mg) and 9 (25%, 12.5 mg). Analytical Data of Compound 10 Colorless solid; mp 63.0–64.0 °C (hexane). ¹H NMR (400 MHz, CDCl₃): δ = 7.31 (1 H, td, J = 1.2, 8.0 Hz), 7.41 (2 H, t, J = 8.0 Hz), 7.72 (2 H, m), 7.82 (1 H, ddd, J = 1.6, 3.2, 8.4 Hz), 8.56 (1 H, dd, J = 1.2, 4.8 Hz), 8.73 (1 H, d, J = 2.8 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 121.4, 121.9, 124.2, 124.5, 126.4, 128.0, 132.3, 142.7, 147.0, 148.7, 151.2, 170.8. IR (KBr) 3060, 1527, 1475, 1440, 1428, 1256, 1235, 1021 cm^–1. MS (EI): m/z (%) = 228 (100) [M⁺], 200 (50) [M⁺ – CN]. HRMS: m/z calcd for C₁₂H₈N₂OS: 228.0357; found: 228.0343.
• 10 You F. Twieg RJ. Tetrahedron Lett. 1999; 40: 8759
  CrossrefSearch in Google Scholar
• 11 Crystallographic data including structure factors have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1534272 for compound 14u. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 12 For a related observation see: Sawatlon B. Wititsuwannakul T. Tantirungrotechai Y. Surawatanawong P. Dalton Trans. 2014; 43: 18123
  CrossrefPubMedSearch in Google Scholar

• Supplementary Material