Iridium-Catalyzed C4-Alkylation of 2,6-Di-tert-butylphenol by Using Hydrogen-Borrowing Catalysis

Abstract

An iridium-catalyzed hydrogen-borrowing process has been developed whereby 2,6-di-tert-butylphenol can be alkylated at the C4-position by using a range of primary alcohols (11 examples, 40–93% yield). Following this, a selection of the products obtained underwent retro-Friedel–Crafts reactions to provide para-substituted phenols, which could potentially undergo further synthetic manipulations.

Key words

iridium - catalysis - hydrogen borrowing - phenols - alkylation

• References


For recent reviews, see:
• 1a Dobereiner GE, Crabtree RH. Chem. Rev. 2010; 110: 681
• 1b Bähn S, Imm S, Neubert L, Zhang M, Neumann H, Beller M. ChemCatChem 2011; 3: 1853
• 1c Pan S, Shibata T. ACS Catal. 2013; 3: 704
• 1d Gunanathan C, Milstein D. Science 2013; 341: 1229712
• 1e Ketcham JM, Shin I, Montgomery TP, Krische MJ. Angew. Chem. Int. Ed. 2014; 53: 9142
• 1f Obora Y. ACS Catal. 2014; 4: 3972
• 1g Yang Q, Wang Q, Yu Z. Chem. Soc. Rev. 2015; 44: 2305
• 1h Nandakumar A, Midya SP, Landge VG, Balaraman E. Angew. Chem. Int. Ed. 2015; 54: 11022
• 2a Chan LM. K, Poole DL, Shen D, Healy MP, Donohoe TJ. Angew. Chem. Int. Ed. 2014; 53: 761
• 2b Shen D, Poole DL, Shotton CC, Kornahrens AF, Healy MP, Donohoe TJ. Angew. Chem. Int. Ed. 2015; 54: 1642
• 2c Frost JR, Cheong CB, Akhtar WM, Caputo DF. J, Stevenson NG, Donohoe TJ. J. Am. Chem. Soc. 2015; 137: 15664
• 3 Weissemel K, Arpe H.-J In Industrial Organic Chemistry . 3rd ed. Wiley-VCH; Weinheim: 1997: 358
• 4 Kornblum N, Seltzer R. J. Am. Chem. Soc. 1961; 83: 3668
• 5a Lederer L. J. Prakt. Chem. 1894; 50: 223
• 5b Manasse O. Ber. Dtsch. Chem. Ges. 1894; 27: 2409
• 6a Lee D.-H, Kwon K.-H, Yi CS. J. Am. Chem. Soc. 2012; 134: 7325
• 6b Walton JW, Williams JM. J. Angew. Chem. Int. Ed. 2012; 51: 12166
• 7 Chen Z, Zeng H, Girard SA, Wang F, Chen N, Li C.-J. Angew. Chem. Int. Ed. 2015; 54: 14487
• 8a For ¹H NMR data for 3, see: Baik W, Lee HJ, Yoo CH, Jung JW, Kim BH. J. Chem. Soc., Perkin Trans. 1 1997; 587
• 8b For ¹H NMR data for 4, see: Barton B, Logie CG, Schoonees BM, Zeelie B. Org. Process Res. Dev. 2005; 9: 62

Bi(cyclohexadienylidene)dione 4 is not isolable, but has been previously characterized in solution by ¹H NMR spectroscopy; see:
• 9a Winstein S, Filar LJ. Tetrahedron Lett. 1960; 9
• 9b Dyall LK, Winstein S. J. Am. Chem. Soc. 1972; 94: 2196
• 10 Although not observed in the 1H NMR spectrum of the crude product, it is likely that addition of MeOH to the benzoquinone methide is also a competitive process; as a result, elimination of methoxide may also be required prior to reduction. See: Omura K. J. Org. Chem. 1991; 56: 921
• 11a Gabrielsson AA, van Leeuwen PP, Kaim WW. Chem. Commun. 2006; 4926
• 11b Jiang B, Feng Y, Ison EA. J. Am. Chem. Soc. 2008; 130: 14462
• 12a Friedel C, Crafts JM. J. Chem. Soc. 1877; 32: 725
• 12b Friedel C, Crafts JM. Bull. Soc. Chim. Fr. 1877; 530
• 13 Application of this methodology to other phenols has so far proven limited.
• 14a Matsuura BS, Keylor MH, Li B, Lin Y, Allison S, Pratt DA, Stephenson CR. J. Angew. Chem. Int. Ed. 2015; 54: 3754
• 14b Saleh SA, Tashtoush HI. Tetrahedron 1998; 54: 14157
• 15 At this stage we cannot comment with any certainty whether an iridium mono- or dihydride species is formed.
• 16 Phillips JP, Gillmore JG, Schwartz P, Brammer LE. Jr, Berger DJ, Tanko JM. J. Am. Chem. Soc. 1998; 120: 195
• 17 Nishinaga A, Nakamura K, Matsuura T, Rieker A, Koch D, Griesshammer R. Tetrahedron 1979; 35: 2493