Dearomatization of a 3-Hydroxypyridine Through an Unexpected Oxidative Deformylation Process: An Entry to Azacyclohexadienones

Abstract

Phenols are well-known precursors of cyclohexadienones, which have widespread applications in organic synthesis. In contrast, their hydroxypyridine counterparts have not been explored yet. An unprecedented oxidative dearomatization of a 3-hydroxypyridine involving an unexpected deformylation step is reported. The chemical reactivity of the resulting unreported azacyclohexadiene-type compound was also explored.

Key words

hydroxypyridines - oxidation - hypervalent iodine - phenyliodine diacetate - azacyclohexadienones

• References and Notes

• 1 Magdziak D, Meek SJ, Pettus TR. Chem. Rev. 2004; 104: 1383
• 2 Quideau S, Pouységu L, Peixoto PA, Deffieux D. In Hypervalent Iodine Chemistry . Wirth T. Springer International; Cham: 2016: 25
• 3 Signo K, Mammasse Z, Canesi S. J. Org. Chem. 2020; 85: 2832
• 4 Moon NG, Harned AM. Org. Biomol. Chem. 2017; 15: 1876
• 5 Liu Q, Rovis T. J. Am. Chem. Soc. 2006; 128: 2552
• 6 Sawama Y, Masuda M, Nakatani R, Yokoyama H, Monguchi Y, Dohi T, Kita Y, Sajiki H. Adv. Synth. Catal. 2016; 358: 3683
• 7 Ohkata K, Tamura Y, Shetuni BB, Takagi R, Miyanaga W, Kojima S, Paquette LA. J. Am. Chem. Soc. 2004; 126: 16783
• 8 Trân-Huu-Dâu M.-E, Wartchow R, Winterfeldt E, Wong Y.-S. Chem. Eur. J. 2001; 7: 2349
• 9 Taveras GA. Tetrahedron Lett. 1988; 29: 1103
• 10 Moon NG, Harned AM. Org. Lett. 2015; 17: 2218
• 11 L’Homme C, Menard M.-A, Canesi S. J. Org. Chem. 2014; 79: 8481
• 12 Jacquemot G, Maertens G, Canesi S. Chem. Eur. J. 2015; 21: 7713
• 13 Maertens G, Canesi S. Chem. Eur. J. 2016; 22: 7090
• 14 Maertens G, Deruer E, Denis M, Canesi S. J. Org. Chem. 2020; 85: 6098−6108
• 15 Lipshutz BH, Amorelli B. J. Am. Chem. Soc. 2009; 131: 1396
• 16 Lee D, Kondo H, Kuwayama Y, Takahashi K, Arima S, Omura S, Ohtawa M, Nagamitsu T. Tetrahedron 2019; 75: 3178
• 17 Jouanno L.-A, Tognetti V, Joubert L, Sabot C, Renard P.-Y. Org. Lett. 2013; 15: 2530
• 18 Sabot C, Oueis E, Brune X, Renard P.-Y. Chem. Commun. 2012; 48: 768
• 19 Jouanno L.-A, Di Mascio V, Tognetti V, Joubert L, Sabot C, Renard P.-Y. J. Org. Chem. 2014; 79: 1303
• 20 Yang PS, Tsai MT, Tsai MH, Ong CW. Chem. Asian J. 2015; 10: 849
• 21 Andrews IP, Lewis NJ, McKillop A, Wells AS. Heterocycles 1996; 43: 1151
• 22 Pouységu L, Deffieux D, Quideau S. Tetrahedron 2010; 66: 2235
• 23 Wenderski TA, Hoarau C, Mejorado L, Pettus TR. Tetrahedron 2010; 66: 5873
• 24 Traoré M, Ahmed-Ali S, Peuchmaur M, Wong Y.-S. Tetrahedron 2010; 66: 5863
• 25 Guérard KC, Sabot C, Beaulieu M.-A, Giroux M.-A, Canesi S. Tetrahedron 2010; 66: 5893
• 26 Liang H, Ciufolini MA. Tetrahedron 2010; 66: 5884
• 27 Tamura Y, Yakura T, Haruta J, Kita Y. J. Org. Chem. 1987; 52: 3927
• 28 2,6-Dimethoxy-6-methylpyridin-3(6H)-one (2a); Typical Procedure A solution of PhI(OAc)₂ (500 mg, 1.538 mmol, 2.14 equiv) in MeOH (1.5 mL) was added dropwise from a pipette to a stirred solution of diol 1 (100 mg, 0.719 mmol) in MeOH (1.5 mL) under air at rt, and the mixture was stirred for 15 min while it turned a yellow color. When the reaction was complete (TLC), the mixture was concentrated under reduced pressure and the crude product was purified by flash-column chromatography [silica gel, cyclohexane–EtOAc (7:3)] to give a yellow oil; yield: 73 mg (60%). IR (neat): 2990, 2948, 2829, 1750, 1696, 1646, 1443, 1328, 1204 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.34 (d, J = 10.30 Hz, 1 H), 6.44 (d, J = 10.12 Hz, 1 H), 3.87 (s, 3 H), 3.21 (s, 3 H), 1.55 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.1, 159.0, 155.4, 129.0, 86.2, 53.8, 51.7, 28.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₈H₁₂NO₃:170.0817; found: 170.0813.
• 29 Mal D, Pahari P, Senapati BK. Tetrahedron Lett. 2005; 46: 2097
• 30 Takagi R, Nishi T. Org. Biomol. Chem. 2015; 13: 11039
• 31 Harry NA, Saranya S, Krishnan KK, Anilkumar G. Asian J. Org. Chem. 2017; 6: 945
• 32 Yang C.-S, Liao C.-C. Org. Lett. 2007; 9: 4809