Scope and Limitations of the Palladium-Catalyzed Direct 1,2-Diheteroarylation of 1,2-Dihalobenzene Derivatives

Abstract

The reactivity of 1,2-dihalobenzenes in palladium-catalyzed C–H bond functionalization is more difficult to control than that of 1,3- and 1,4-dihalobenzenes because of a possible Pd 1,4-migration during the second catalytic cycle. With C3-substituted heteroarenes this 1,4-palladium migration is not possible and the reaction allows the synthesis of a wide variety of functionalized 1,2-heteroarylated benzene derivatives in high yields. Conversely, only a few heteroarenes with a free C3 position, such as thiazoles, furans and imidazoles, allow the preparation of 1,2-heteroarylated benzenes. Despite these limitations, this one-pot procedure employing an easily available catalyst [Pd(OAc)₂] and an inexpensive base (KOAc) provides a very simple method for the preparation of several 1,2-heteroarylated benzenes.

Key words

C–H functionalization - 1,2-dihalobenzenes - heteroarenes - homogeneous catalysis - palladium

Publication History

Received: 08 September 2022

Accepted after revision: 17 November 2022

Accepted Manuscript online:
17 November 2022

Article published online:
08 December 2022

• References


For reviews on metal-catalyzed C–H bond functionalization, see:
• 1a Ackermann L. Chem. Rev. 2011; 111: 1315
• 1b Arockiam PB, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879
• 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 Ruiz S, Villuendas P, Urriolabeitia EP. Tetrahedron Lett. 2016; 57: 3413
• 1f Agasti S, Dey A, Maiti D. Chem. Commun. 2017; 53: 6544
• 1g Gensch T, James MJ, Dalton T, Glorius F. Angew. Chem. Int. Ed. 2018; 57: 2296
• 1h Kalepu J.; Gandeepan P.; Ackermann L.; Pilarski L. T. Chem. Sci. 2018, 9, 4203.
• 1i Hirano K, Miura M. Chem. Sci. 2018; 9: 22
• 1j Prendergast AM, McGlacken GP. Eur. J. Org. Chem. 2018; 6068
• 1k Gandeepan P, Mueller T, Zell D, Cera G, Warratz S, Ackermann L. Chem. Rev. 2019; 119: 2192
• 1l Hagui W, Doucet H, Soulé J.-F. Chem 2019; 5: 2006
• 1m Mao S, Li H, Shi X, Soulé J.-F, Doucet H. ChemCatChem 2019; 11: 269
• 1n Rej S, Ano Y, Chatani N. Chem. Rev. 2020; 120: 1788
• 1o Huang H.-Y, Benzai A, Shi X, Doucet H. Chem. Rec. 2021; 21: 343
• 1p Saha A, Shankar M, Sau S, Sahoo AK. Chem. Commun. 2022; 58: 4561
• 2a Akita Y, Inoue A, Yamamoto K, Ohta A, Kurihara T, Shimizu M. Heterocycles 1985; 23: 2327
• 2b Ohta A, Akita Y, Ohkuwa T, Chiba M, Fukunaga R, Miyafuji A, Nakata T, Tani N, Aoyagi Y. Heterocycles 1990; 31: 1951
• 2c Aoyagi Y, Inoue A, Koizumi I, Hashimoto R, Tokunaga K, Gohma K, Komatsu J, Sekine K, Miyafuji A, Kunoh J, Honma R, Akita Y, Ohta A. Heterocycles 1992; 33: 257

For selected examples of direct arylations of furans, see:
• 3a Parisien M, Valette D, Fagnou K. J. Org. Chem. 2005; 70: 7578
• 3b Liégaut B, Lapointe D, Caron L, Vlassova A, Fagnou K. J. Org. Chem. 2009; 74: 1826
• 3c Dong JJ, Roger J, Požgan F, Doucet H. Green Chem. 2009; 11: 1832

For selected examples of direct arylations of thiophenes, see:
• 4a Masui K, Mori A, Okano K, Takamura K, Kinoshita M, Ikeda T. Org. Lett. 2004; 6: 2011
• 4b David E, Pellet-Rostaing S, Lemaire M. Tetrahedron 2007; 63: 8999
• 4c Chiong HA, Daugulis O. Org. Lett. 2007; 9: 1449
• 4d Roger J, Požgan F, Doucet H. Green Chem. 2009; 11: 425
• 4e Liégault B, Petrov I, Gorlesky SI, Fagnou K. J. Org. Chem. 2010; 75: 1047

For selected examples of direct arylations of pyrroles or indoles, see:
• 5a Bellina F, Cauteruccio S, Rossi R. Eur. J. Org. Chem. 2006; 1379
• 5b Wang X, Gribkov DV, Sames D. J. Org. Chem. 2007; 72: 1476
• 5c Roger J, Doucet H. Adv. Synth. Catal. 2009; 351: 1977

For selected examples of direct arylations of thiazoles, see:
• 6a Mori A, Sekiguchi A, Masui K, Shimada T, Horie M, Osakada K, Kawamoto M, Ikeda T. J. Am. Chem. Soc. 2003; 125: 1700
• 6b Yokooji A, Okazawa T, Satoh T, Miura M, Nomura M. Tetrahedron 2003; 59: 5685
• 6c Turner GL, Morris JA, Greaney MF. Angew. Chem. Int. Ed. 2007; 46: 7996
• 6d Campeau L.-C, Bertrand-Laperle M, Leclerc J.-P, Villemure E, Gorelsky S, Fagnou K. J. Am. Chem. Soc. 2008; 130: 3276
• 6e Dong JJ, Roger J, Verrier C, Martin T, Le Goff R, Hoarau C, Doucet H. Green Chem. 2010; 12: 2053

For selected examples of direct arylations of imidazoles, see:
• 7a Bellina F, Cauteruccio S, Di Fiore A, Rossi R. Eur. J. Org. Chem. 2008; 5436
• 7b Bellina F, Cauteruccio S, Di Fiore A, Marchietti C, Rossi R. Tetrahedron 2008; 64: 6060
• 8 For selected examples of direct arylations of isoxazoles, see: Fall Y, Reynaud C, Doucet H, Santelli M. Eur. J. Org. Chem. 2009; 4041

For examples of palladium-catalyzed direct arylations using 1,3- and 1,4-dihalobenzenes, see:
• 9a Mashraqui SH, Ashraf M, Ghadigaonkar SG. Synlett 2006; 2423
• 9b Ackermann L, Althammer A, Mayer P. Synthesis 2009; 3493
• 9c Kowada T, Ohe K. Bull. Korean Chem. Soc. 2010; 31: 577
• 9d Martins A, Candito DA, Lautens M. Org. Lett. 2010; 12: 5186
• 9e Schipper DJ, Fagnou K. Chem. Mater. 2011; 23: 1594
• 10a Derridj F, Gottumukkala AL, Djebbar S, Doucet H. Eur. J. Inorg. Chem. 2008; 2550
• 10b Liu S.-Y, Wang D.-G, Zhong A.-G, Wen H.-R. Org. Chem. Front. 2018; 5: 653
• 10c Matsidik R, Takimiya K. Chem. Asian J. 2019; 14: 1651
• 11 Liu L, Doucet H. Adv. Synth. Catal. 2022; 364: 2783
• 12a For reviews on 1,4-migration of Pd in catalytic organometallic reactions, see: Ma S, Gu Z. Angew. Chem. Int. Ed. 2005; 44: 7512
• 12b Yasui Y. J. Synth. Org. Chem., Jpn. 2008; 66: 251
• 12c Dong X, Wang H, Liu H, Wang F. Org. Chem. Front. 2020; 7: 3530
• 13 For Hammett constants, see: Hansch C, Leo A, Taft RW. Chem. Rev. 1991; 91: 165
• 14 For examples of 1,8-diheteroarylations of 1,8-dihalonaphthalenes using Stille coupling, see: Li M, Zhang X, Zhen S, Xu J. New J. Chem. 2021; 45: 1795
• 15 Han J.-L, Qin Y, Ju C.-W, Zhao D. Angew. Chem. Int. Ed. 2020; 59: 6555
• 16 Wu H, Fang R, Tao J, Wang D, Qiao X, Yang X, Hartl F, Li H. Chem. Commun. 2017; 53: 751

For the concerted–metalation deprotonation mechanism, see:
• 17a Davies DL, Donald SM. A, Macgregor SA. J. Am. Chem. Soc. 2005; 127: 13754
• 17b Lafrance M, Fagnou K. J. Am. Chem. Soc. 2006; 128: 16496
• 17c Gorelsky SI, Lapointe D, Fagnou K. J. Am. Chem. Soc. 2008; 130: 10848
• 17d Gorelsky SI. Coord. Chem. Rev. 2013; 257: 153
• 17e Davies DL, Macgregor SA, McMullin CL. Chem. Rev. 2017; 117: 8649
• 17f Alharis RA, McMullin CL, Davies DL, Singh K, Macgregor SA. J. Am. Chem. Soc. 2019; 141: 8896