Hydroxymethyl as Directing Group for the Regioselective Palladium-Catalyzed C–H Bond C2-Arylation of a C3-Substituted Furan

Abstract

The reaction outcome of the palladium-catalyzed C–H arylation of 3-(hydroxymethyl)furan was investigated. The hydroxymethyl group at the C3 position of the furan proved to be a powerful directing group for controlling regioselective direct arylation at the C2 position, while the C5-position and the hydroxymethyl function of the furan ring remained unaffected. The reaction tolerates a very wide variety of electron-poor or rich aryl bromides, bearing substituents at the para- or meta-positions, as well as heteroaryl bromides. It should be noted that, for this coupling reaction, an air-stable palladium catalyst and an inexpensive base were used. Using an excess of specific aryl bromides, 3-(hydroxymethyl)furan can also be diarylated at positions 2 and 5.

Key words

arylation - C–H bond functionalization - C–C bond formation - furans - homogeneous catalysis - palladium

Publication History

Received: 18 November 2024

Accepted after revision: 30 December 2024

Article published online:
05 March 2025

• References


For reviews on metal-catalyzed C–H bond functionalization, see:
• 1a Chiusoli GP, Catellani M, Costa M, Motti E, Della Ca N, Maestri G. Coord. Chem. Rev. 2010; 254: 456
• 1b Kuhl N, Hopkinson MN, Wencel-Delord J, Glorius F. Angew. Chem. Int. Ed. 2012; 51: 10236
• 1c Rossi R, Bellina F, Lessi M, Manzini C. Adv. Synth. Catal. 2014; 356: 17
• 1d Theveau L, Schneider C, Fruit C, Hoarau C. ChemCatChem 2016; 8: 3183
• 1e Agasti S, Dey A, Maiti D. Chem. Commun. 2017; 53: 6544
• 1f Gensch T, James MJ, Dalton T, Glorius F. Angew. Chem. Int. Ed. 2018; 57: 2296
• 1g Kalepu J, Gandeepan P, Ackermann L, Pilarski LT. Chem. Sci. 2018; 9: 4203
• 1h Hirano K, Miura M. Chem. Sci. 2018; 9: 22
• 1i Gandeepan P, Mueller T, Zell D, Cera G, Warratz S, Ackermann L. Chem. Rev. 2019; 119: 2192
• 1j Mao S, Li H, Shi X, Soulé J.-F, Doucet H. ChemCatChem 2019; 11: 269
• 1k Hagui W, Doucet H, Soulé J.-F. Chem 2019; 5: 2006
• 1l Rej S, Ano Y, Chatani N. Chem. Rev. 2020; 120: 1788
• 1m Huang H.-Y, Benzai A, Shi X, Doucet H. Chem. Rec. 2021; 21: 343
• 1n Rossi R, Ciofalo M. Curr. Org. Chem. 2022; 26: 215
• 1o Docherty JH, Lister TM, Mcarthur G, Findlay MT, Domingo-Legarda P, Kenyon J, Choudhary S, Larrosa I. Chem. Rev. 2023; 123: 7692

For Pd-catalyzed direct arylation with heteroarenes bearing unprotected hydroxymethyl substituent, see:
• 2a Chuprakov S, Chernyak N, Dudnik AS, Gevorgyan V. Org. Lett. 2007; 9: 2333
• 2b Roger J, Pozgan F, Doucet H. Adv. Synth. Catal. 2010; 352: 696
• 2c Dong JJ, Roy D, Roy RJ, Ionita M, Doucet H. Synthesis 2011; 3530
• 2d Saito Y, Kobayashi Y, Yoshida N, Goto M, Nakagawa-Goto K. J. Org. Chem. 2021; 86: 7092
• 3a Davies DL, Donald SM. A, Macgregor SA. J. Am. Chem. Soc. 2005; 127: 13754
• 3b Lafrance M, Fagnou K. J. Am. Chem. Soc. 2006; 128: 16496
• 3c Lapointe D, Fagnou K. Chem. Lett. 2010; 39: 1118
• 3d Ackermann L. Chem. Rev. 2011; 111: 1315
• 3e Gorelsky SI, Lapointe D, Fagnou K. J. Org. Chem. 2012; 77: 658
• 3f Gorelsky SI. Coord. Chem Rev. 2013; 257: 153
• 3g Davies DL, Macgregor SA, McMullin CL. Chem. Rev. 2017; 117: 8649
• 3h Rogge T, Oliveira JC. A, Kuniyil R, Hu L, Ackermann L. ACS Catal. 2020; 10: 10551
• 4 For a review on the regioselectivity of Pd-catalyzed direct arylation, see: Bheeter CB, Chen L, Soulé J.-F, Doucet H. Cat. Sci. Technol. 2016; 5: 2005
• 5 Ohta A, Akita Y, Ohkuwa T, Chiba M, Fukunaga R, Miyafuji A, Nakata T, Tani N, Aoyagi Y. Heterocycles 1990; 31: 1951

For selected examples of Pd-catalyzed C–H bond arylation of furans, see:
• 6a McClure MS, Glover B, McSorley E, Millar A, Osterhout MH, Roschangar F. Org. Lett. 2001; 3: 1677
• 6b Parisien M, Valette D, Fagnou K. J. Org. Chem. 2005; 70: 7578
• 6c Battace A, Lemhadri M, Zair T, Doucet H, Santelli M. Organometallics 2007; 26: 472
• 6d Beccalli EM, Broggini G, Martinelli M, Sottocornola S. Synthesis 2008; 136
• 6e Liégaut B, Lapointe D, Caron L, Vlassova A, Fagnou K. J. Org. Chem. 2009; 74: 1826
• 6f Fu HY, Doucet H. Eur. J. Org. Chem. 2011; 7163
• 6g Mao S, Shi X, Soule J.-F, Doucet H. Adv. Synth. Catal. 2018; 360: 3306
• 6h Al Mamari HH, Groselj U, Pozgan F, Brodnik H. J. Org. Chem. 2021; 86: 3138
• 6i Liu L, Cordier M, Roisnel T, Doucet H. Org. Chem. Front. 2023; 10: 1441

For direct C2-arylations of 3-bromofuran, see:
• 7a Sasmal A, Roisnel T, Bera JK, Doucet H, Soule JF. Synthesis 2019; 51: 3241
• 7b Jang JH, Ahn S, Park SE, Kim S, Byon HR, Joo JM. Org. Lett. 2020; 22: 1280
• 8 For direct C2-arylations of a 3-(furan-3-yl)acrylate, see: Chen L, Bruneau C, Dixneuf PH, Doucet H. Tetrahedron 2013; 69: 4381
• 9 For direct C2-arylations of 3-formylfuran, see: Battace A, Lemhadri M, Zair T, Doucet H, Santelli M. Organometallics 2007; 26: 472

For direct C2-arylations of a furan-3-carboxylate, see:
• 10a Glover B, Harvey KA, Liu B, Sharp MJ, Tymoschenko MF. Org. Lett. 2003; 5: 301
• 10b Dong JJ, Roy D, Roy RJ, Ionita M, Doucet H. Synthesis 2011; 3530
• 11 Cantat T, Génin E, Giroud C, Meyer G, Jutand A. J. Organomet. Chem. 2003; 687: 365
• 12 Laidaoui N, Roger J, Miloudi A, El Abed D, Doucet H. Eur. J. Org. Chem. 2011; 4373