Synthesis of Alkyl Aryl Ethers by O-Arylation of Alcohols with Diaryliodonium Salts: Scope, Limitations, and Mechanism

This manuscript is dedicated to the memory of Professor Keith Fagnou.

Abstract

We describe the development of a C–O coupling reaction between aryl(2,4,6-trimethoxyphenyl)iodonium salts and aliphatic alcohols under weak base conditions. The scope of the reaction is presented, with 16 examples ranging in yield from moderate to high (54–96%). The limitations of the reaction are also presented. Mechanistic experiments reveal a complex network of reactions that include side reactions that generate arynes and oxidize the alcohol nucleophile.

Key words

arylation - ethers - alcohols - diaryliodonium compounds - ligand coupling - C–O coupling

Publication History

Received: 01 September 2023

Accepted after revision: 25 October 2023

Accepted Manuscript online:
25 October 2023

Article published online:
21 November 2023

• References and Notes

• 1 New address: Analog Devices, 14320 SW Jenkins Rd, Beaverton, OR 97005.
• 2a Enthaler S, Company A. Chem. Soc. Rev. 2011; 40: 4912
• 2b Brown DG, Boström J. J. Med. Chem. 2016; 59: 4443
• 2c Evano G, Wang JJ, Nitelet A. Org. Chem. Front. 2017; 4: 2480
• 3a March J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed. Wiley; New York: 1992: 641
• 3b Ando S, Tsuzaki M, Ishizuka T. J. Org. Chem. 2020; 85: 11181

For examples of copper catalysis, see:
• 4a Jones GO, Liu P, Houk KN, Buchwald SL. J. Am. Chem. Soc. 2010; 132: 6205
• 4b Maiti D. Chem. Commun. 2011; 47: 8340
• 4c Guo Y, Fan X.-M, Nie M, Liu H.-W, Liao D.-H, Pan X.-D, Ji Y.-F. Eur. J. Org. Chem. 2015; 4744
• 4d Zheng Y, Zou W, Luo L, Chen J, Lin S, Sun Q. RSC Adv. 2015; 5: 66104
• 4e Chen Z, Jiang Y, Zhang L, Guo Y, Ma D. J. Am. Chem. Soc. 2019; 141: 3541
• 4f Ritwika R, Hartwig JF. Angew. Chem. Int. Ed. 2021; 60: 8203

For examples of palladium catalysis, see:
• 4g Gowrisankar S, Sergeev A, Anbarasan P, Spannenbeig A, Neumann H, Beller M. J. Am. Chem. Soc. 2010; 132: 11592
• 4h Wu X, Fors BP, Buchwald SL. Angew. Chem. Int. Ed. 2011; 50: 9943
• 4i Gowrisankar S, Neumann H, Beller M. Chem. Eur. J. 2012; 18: 2498
• 4j Cheung CW, Buchwald SL. Org. Lett. 2013; 15: 3998
• 4k Rangarajan TM, Singh R, Brahma R, Devi K, Singh RP, Singh RP, Prasad AK. Chem. Eur. J. 2014; 20: 14218
• 4l Sawatzky RS, Hargreaves BK. V, Stradiotto M. Eur. J. Org. Chem. 2016; 2444
• 4m Zhang H, Ruiz-Castillo P, Buchwald SL. Org. Lett. 2018; 20: 1580
• 4n Laffoon JD, Chan VS, Fickes MG, Kotecki B, Ickes AR, Henle J, Napolitano JG, Fanczyk TS, Dunn TB, Barnes DM, Haight AR, Henry RF, Shekhar S. ACS Catal. 2019; 9: 11691
• 4o Zhang H, Ruiz-Castillo P, Schuppe AW, Buchwald SL. Org. Lett. 2020; 22: 5369
• 5a Terrett JA, Cuthbertson JD, Shurtleff VW, MacMillan DW. C. Nature 2015; 524: 330
• 5b MacQueen PM, Tassone JP, Diaz C, Stradiotto M. J. Am. Chem. Soc. 2018; 140: 5023
• 5c Zhou Q.-Q, Lu F.-D, Liu D, Lu L.-Q, Xiao W.-J. Org. Chem. Front. 2018; 5: 3098
• 5d Zhao X, Deng C, Meng D, Ji H, Chen C, Song W, Zhao J. ACS Catal. 2020; 10: 15178
• 5e Morrison KM, McGuire RT, Ferguson MJ, Stradiotto M. ACS Catal. 2021; 11: 10878
• 5f Zhang H.-J, Chen L, Oderinde MS, Edwards JT, Kawamata Y, Baran PS. Angew. Chem. Int. Ed. 2021; 60: 20700
• 6a Beringer FM, Brierley A, Drexler M, Gindler EM, Lumpkin CC. J. Am. Chem. Soc. 1953; 75: 2708
• 6b Lubinkowski JJ, Knapczyk JW, Calderon JL, Petit LR, McEwen WE. J. Org. Chem. 1975; 40: 3010
• 6c Lindstedt E, Ghosh R, Olofsson B. Org. Lett. 2013; 15: 6070
• 6d Ghosh R, Lindstedt E, Jalalian N, Olofsson B. ChemistryOpen 2014; 3: 54
• 6e Sundalam SK, Stuart DR. J. Org. Chem. 2015; 80: 6456
• 6f Tolnai GL, Nilsson UJ, Olofsson B. Angew. Chem. Int. Ed. 2016; 55: 11226
• 6g Li J, Wang Z, Lu X, Lin J, Liu L, Zhao Y. Lett. Org. Chem. 2019; 16: 485
• 7a Hilton MC, Dolewski RD, McNally A. J. Am. Chem. Soc. 2016; 138: 13806
• 7b Anderson RG, Jett BM, NcNally A. Angew. Chem. Int. Ed. 2018; 57: 12514
• 8 Yoshida T, Honda Y, Morofuji T, Kano N. J. Org. Chem. 2022; 87: 7565
• 9 Yaroshevsky AA. Geochem. Int. 2006; 44: 48
• 10a Seidl TL, Sundalam SK, McCullough B, Stuart DR. J. Org. Chem. 2016; 81: 1998
• 10b Sandtorv AH, Stuart DR. Angew. Chem. Int. Ed. 2016; 55: 15812
• 10c Carreras V, Sandtorv AH, Stuart DR. J. Org. Chem. 2017; 82: 1279
• 10d Seidl TL, Stuart DR. J. Org. Chem. 2017; 82: 11765
• 10e Basu S, Sandtorv AH, Stuart DR. Beilstein J. Org. Chem. 2018; 14: 1034
• 10f Seidl TL, Moment A, Orella C, Vickery T, Stuart DR. Org. Synth. 2019; 96: 137
• 10g Gallagher RT, Basu S, Stuart DR. Adv. Synth. Catal. 2020; 362: 320
• 10h Pou S, Dodean RA, Frueh L, Liebman KM, Gallagher RT, Jin H, Jacobs RT, Nilsen A, Stuart DR, Doggett JS, Riscoe MK, Winter RW. Org. Process Res. Dev. 2021; 25: 1841
• 10i Nilova A, Metze B, Stuart DR. Org. Lett. 2021; 23: 4813
• 10j Metze BE, Bhattacharjee A, McCormick TM, Stuart DR. Synthesis 2022; 54: 4989
• 11 Stridfeldt E, Lindstedt E, Reitti M, Blid J, Norrby P.-O, Olofsson B. Chem. Eur. J. 2017; 23: 13249
• 12 Minegishi S, Kobayashi S, Mayr H. J. Am. Chem. Soc. 2004; 126: 5174
• 13a Lancer KM, Wiegand GH. J. Org. Chem. 1976; 41: 3360
• 13b Malmgren J, Santoro S, Jalalian N, Himo F, Olofsson B. Chem. Eur. J. 2013; 19: 10334
• 14 See the Supporting Information for further details.
• 15a Akiyama T, Imasaki Y, Kawanisi M. Chem. Lett. 1974; 229
• 15b Cadogan JI. G, Rowley AG, Sharp JT, Sledzinski B, Wilson NH. J. Chem. Soc., Perkin Trans. 1 1975; 1072
• 15c Sundalam S, Nilova A, Seidl TL, Stuart DR. Angew. Chem. Int. Ed. 2016; 55: 8431
• 15d Wang M, Huang Z. Org. Biomol. Chem. 2016; 14: 10185
• 15e Zhang Z, Wu X, Han J, Wu W, Wang L. Tetrahedron Lett. 2018; 59: 1737
• 15f Chen H, Han J, Wang L. Beilstein J. Org. Chem. 2018; 14: 354
• 15g Dohi T, Hayashi T, Ueda S, Shoji T, Komiyama K, Takeuchi H, Kita Y. Tetrahedron 2019; 75: 3617
• 15h Murai M, Ogita T, Takai K. Chem. Commun. 2019; 55: 2332
• 15i Nilova A, Sibald PA, Valente EJ, González-Montiel GA, Richardson HC, Brown KS, Cheong PH.-Y, Stuart DR. Chem. Eur. J. 2021; 27: 7168
• 15j Yuan H, Yin W, Hu J, Li Y. Nat. Commun. 2023; 14: 1841
• 15k Liu M, Jiang H, Tang J, Ye Z, Zhang F, Wu Y. Org. Lett. 2023; 25: 2777
• 15l Li X, Chen H, Liu X, Wang L, Han J. ChemistrySelect 2023; 8: e202301890
• 16 Willoughby PH, Niu D, Wang T, Haj MK, Cramer CJ, Hoye TR. J. Am. Chem. Soc. 2014; 136: 13657
• 17 Medina JM, Mackey JL, Garg NK, Houk KN. J. Am. Chem. Soc. 2014; 136: 15798
• 18 C–O Coupling; General Procedure The appropriate aryl(TMP)iodonium tosylate 1a–l (0.5 mmol, 1 equiv), Cs₂CO₃ (1.5 mmol, 3 equiv), alcohol 2a–f (0.75 mmol, 1.5 equiv), and toluene (2.5 mL) were added to an 8 mL vial, equipped with a magnetic stirrer bar and sealed with a cap. The vial was placed in a preheated aluminum block set to 55 °C, and the mixture was stirred vigorously for 2 h. The vial was removed from the block and the mixture was partitioned between CH₂Cl₂ and sat. aq NH₄Cl. The resulting organic solution was concentrated under reduced pressure, and the residue was purified by flash column chromatography (silica gel, 0–3% EtOAc–hexane).
• 19 Benzyl 4-Chlorophenyl Ether (3a) White solid; yield 82.3 mg (75%). ¹H NMR (400 MHz, CDCl₃): δ = 7.42–7.32 (m, 5 H), 7.22 (d, J = 9.0 Hz, 2 H), 6.88 (d, J = 9.0 Hz, 2 H), 5.02 (s, 2 H). ¹³C {¹H} NMR (101 MHz, CDCl₃): δ = 157.4, 136.6, 129.4, 128.7, 128.1, 127.5, 125.8, 116.2, 70.3. 4-Nitrophenyl Pentyl Ether (3g) Yellow oil; yield: 102.8 mg (98%). ¹H NMR (400 MHz, CDCl₃): δ = 8.19–8.15 (m, 2 H), 6.96–6.92 (m, 2 H), 4.04 (t, J = 6.5 Hz, 2 H), 1.86–1.79 (m, 2 H), 1.49–1.35 (m, 4 H), 0.94 (t, J = 7.1 Hz, 3 H). ¹³C {¹H} NMR (101 MHz, CDCl₃): δ = 164.3, 141.2, 125.8, 114.4, 68.9, 28.7, 28.0, 22.4, 14.0. 4-Bromophenyl 2,2,2-Trifluoroethyl Ether (3m) Off-white solid; yield: 89.8 mg (70%). ¹H NMR (400 MHz, CDCl₃): δ = 7.41 (d, J = 9.0 Hz, 2 H), 6.82 (d, J = 8.9 Hz, 2 H), 4.31 (q, J = 8.1 Hz, 2 H). ¹³C {1 H} NMR (101 MHz, CDCl₃): δ = 156.5, 132.6, 123.2 (q, J = 278.1 Hz), 116.8, 115.0, 66.0 (q, J = 35.8 Hz).