Recent Developments in the Chemistry of Heteroaromatic N-Oxides

Abstract

Selected developments in the chemistry of heteroaromatic N-oxides since 2001 are presented in this review. The use of these N-oxides, both in late-transition-metal-catalyzed oxidations of carbon–carbon triple bonds and in regioselective C–H functionalizations of the heteroarene, are contemporary topics of interest and the focus of the discussion.

1 Introduction

2 Synthesis of Heteroaromatic N-Oxides

2.1 Direct Oxidation of Hindered Heteroarenes

2.2 Through Construction of Heteroaromatic Rings

3 Heteroaromatic N-Oxides as Oxidants

3.1 Alkyne Oxidation

3.2 Allene Oxidation

3.3 Carbene Oxidation

4 Heteroaromatic N-Oxides as Substrates

4.1 Deoxygenative ortho-C–H Functionalization with Prior Activation

4.2 Deoxygenative ortho-C–H Functionalization with Nonstabilized Carbanions

4.3 Nondeoxygenative C–H Functionalization

4.3.1 ortho-C–H Functionalization

4.3.2 N-Oxide Directed ortho-Alkyl C–H Functionalization

4.3.3 N-Oxide Directed Remote C–H Functionalization

4.4 1,3-Dipolar Cycloaddition

5 Conclusion and Outlook

Key words

oxidations - alkynes - cycloadditions - carbenes - pyridines

• References

• 1 Chanzy H, Maia E, Perez S. Acta Crystallogr., Sect. B 1982; 38: 852
• 2 Jaffé HH, Doak GO. J. Am. Chem. Soc. 1955; 77: 4441
• 3 Albini A, Pietra S. Heterocyclic N-Oxides . CRC Press; Boca Raton: 1991
• 4 Youssif S. ARKIVOC 2001; (i): 242
• 5 Campeau L.-C, Stuart DR, Leclerc J.-P, Bertrand-Laperle M, Villemure E, Sun H.-Y, Lasserre S, Guimond N, Lecavallier M, Fagnou K. J. Am. Chem. Soc. 2009; 131: 3291
• 6 Brougham P, Cooper MS, Cummerson DA, Heaney H, Thompson N. Synthesis 1987; 1015
• 7 Rong D, Phillips VA, Rubio RS, Ángeles Castro M, Wheelhouse RT. Tetrahedron Lett. 2008; 49: 6933
• 8 Murray RW, Jeyaraman R. J. Org. Chem. 1985; 50: 2847
• 9 Copéret C, Adolfsson H, Khuong T.-AV, Yudin AK, Sharpless KB. J. Org. Chem. 1998; 63: 1740
• 10 Carmeli M, Rozen S. J. Org. Chem. 2005; 70: 2131
• 11 Yeom H.-S, Kim S, Shin S. Synlett 2008; 924
• 12 Pagar VV, Jadhav AM, Liu R.-S. J. Am. Chem. Soc. 2011; 133: 20728
• 13 Shi Z, Koester DC, Boultadakis-Arapinis M, Glorius F. J. Am. Chem. Soc. 2013; 135: 12204
• 14 Lin Y.-S, Liu C.-W, Tsai TY. R. Tetrahedron Lett. 2005; 46: 1859
• 15a Ferguson IJ, Schofield K. J. Chem. Soc., Perkin Trans. 1 1975; 275
• 15b Jasiński M, Mlostoń G, Linden A, Heimgartner H. Helv. Chim. Acta 2008; 91: 1916
• 15c Mlostoń G, Jasiński M, Heimgartner H. Eur. J. Org. Chem. 2011; 2542
• 16 Shibata Y, Kagechika K, Yamaguchi M, Yoshikawa K, Chiba K, Takano H, Akiyama C, Ono M, Nishi M, Kubo H, Kobayashi Y, Usui H. Chem. Pharm. Bull. 2013; 61: 1248
• 17a Goto Y, Yamazaki M, Hamana M. Chem. Pharm. Bull. 1971; 19: 2050
• 17b Bénardeau A, Benz J, Binggeli A, Blum D, Boehringer M, Grether U, Hilpert H, Kuhn B, Märki HP, Meyer M, Püntener K, Raab S, Ruf A, Schlatter D, Mohr P. Bioorg. Med. Chem. Lett. 2009; 19: 2468
• 18 Luo Y.-R. Handbook of Bond Dissociation Energies in Organic Compounds. CRC Press; Boca Raton: 2003
• 19 Eberbach W, Maier W. Tetrahedron Lett. 1989; 30: 5591
• 20a Zhang L, Sun J, Kozmin SA. Adv. Synth. Catal. 2006; 348: 2271
• 20b Fürstner A, Davies PW. Angew. Chem. Int. Ed. 2007; 46: 3410
• 20c Hashmi AS. K. Chem. Rev. 2007; 107: 3180
• 20d Jiménez-Núñez E, Echavarren AM. Chem. Rev. 2008; 108: 3326
• 20e Abu Sohel SM, Liu R.-S. Chem. Soc. Rev. 2009; 38: 2269
• 21 Ye L, Cui L, Zhang G, Zhang L. J. Am. Chem. Soc. 2010; 132: 3258
• 22 Hashmi AS. K. Angew. Chem. Int. Ed. 2010; 49: 5232
• 23 Hashmi AS. K. Gold Bull. 2003; 36: 3
• 24 Cuenca AB, Montserrai S, Hossain KM, Mancha G, Lledos A, Medio-Simon M, Ujaque G, Asensio G. Org. Lett. 2009; 11: 4906
• 25 Doyle MP, McKervey MA, Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides. Wiley; New York: 1998
• 26a Zhang L. Acc. Chem. Res. 2014; 47: 877
• 26b Lu B, Li C, Zhang L. J. Am. Chem. Soc. 2010; 132: 14070
• 26c Ye L, He W, Zhang L. J. Am. Chem. Soc. 2010; 132: 8550
• 26d Vasu D, Hung H.-H, Bhunia S, Gawade SA, Das A, Liu R.-S. Angew. Chem. Int. Ed. 2011; 50: 6911
• 26e Hashmi AS. K, Wang T, Shi S, Rudolph M. J. Org. Chem. 2012; 77: 7761
• 26f Wang L, Xie X, Liu Y. Angew. Chem. Int. Ed. 2013; 52: 13302
• 27 Ji K, Nelson J, Zhang L. Beilstein J. Org. Chem. 2013; 9: 1925
• 28 Bian Z, Marvin CC, Martin SF. J. Am. Chem. Soc. 2013; 135: 10886
• 29 Kong K, Enquist JA, McCallum ME, Smith GM, Matsumaru T, Menhaji-Klotz E, Wood JL. J. Am. Chem. Soc. 2013; 135: 10890
• 30 Luo Y, Ji K, Li Y, Zhang L. J. Am. Chem. Soc. 2012; 134: 17412
• 31 He W, Xie L, Xu Y, Xiang J, Zhang L. Org. Biomol. Chem. 2012; 10: 3168
• 32 Lundgren RJ, Peters BD, Alsabeh PG, Stradiotto M. Angew. Chem. Int. Ed. 2010; 49: 4071
• 33 Bhunia S, Ghorpade S, Huple DB, Liu R.-S. Angew. Chem. Int. Ed. 2012; 51: 2939
• 34 Henrion G, Chavas TE. J, Le Goff X, Gagosz F. Angew. Chem. Int. Ed. 2013; 52: 6277
• 35 Huple DB, Ghorpade S, Liu R.-S. Chem. Eur. J. 2013; 19: 12965
• 36 Murai M, Kitabata S, Okamoto K, Ohe K. Chem. Commun. 2012; 48: 7622
• 37 Liu R, Winston-McPherson GN, Yang Z.-Y, Zhou X, Song W, Guzei IA, Xu X, Tang W. J. Am. Chem. Soc. 2013; 135: 8201
• 38 Sawama Y, Takubo M, Mori S, Monguchi Y, Sajiki H. Eur. J. Org. Chem. 2011; 3361
• 39 Gronnier C, Kramer S, Odabachian Y, Gagosz F. J. Am. Chem. Soc. 2012; 134: 828
• 40 Murahashi S. Ruthenium in Organic Synthesis . Wiley-VCH; Weinheim: 2004
• 41a Madhushaw RJ, Lin M.-Y, Sohel SM. A, Liu R.-S. J. Am. Chem. Soc. 2004; 126: 6895
• 41b Lin M.-Y, Madhushaw RJ, Liu R.-S. J. Org. Chem. 2004; 69: 7700
• 41c Lin M.-Y, Maddirala SJ, Liu R.-S. Org. Lett. 2005; 7: 1745
• 41d Pati K, Liu R.-S. Chem. Commun. 2009; 5233
• 42 Kim I, Lee C. Angew. Chem. Int. Ed. 2013; 52: 10023
• 43 Cossío FP, Arrieta A, Sierra MA. Acc. Chem. Res. 2008; 41: 925
• 44 Kim I, Roh SW, Lee DG, Lee C. Org. Lett. 2014; 16: 2482
• 45 Wang Y, Zheng Z, Zhang L. Angew. Chem. Int. Ed. 2014; 53: 9572
• 46 Chen D.-F, Han Z.-Y, He Y.-P, Yu J, Gong L.-Z. Angew. Chem. Int. Ed. 2012; 51: 12307
• 47 Graf K, Rühl CL, Rudolph M, Rominger F, Hashmi AS. K. Angew. Chem. Int. Ed. 2013; 52: 12727
• 48 Luo Y, Zhang G, Hwang ES, Wilcoxon TA, Zhang L. Beilstein J. Org. Chem. 2011; 7: 596
• 49a Barluenga J, Bernad PL. Jr, Concellón J. Tetrahedron Lett. 1995; 36: 3937
• 49b Barluenga J, Fernández-Marí F, González R, Aguilar E, Revelli GA, Viado AL, Fañanás FJ, Olano B. Eur. J. Org. Chem. 2000; 1773
• 49c Barluenga J, García-Rodríguez J, Martínez S, Suárez-Sobrino AL, Tomás M. Chem. Eur. J. 2006; 12: 3201
• 49d Barluenga J, Martínez S, Suárez-Sobrino AL, Tomás M. Organometallics 2006; 25: 2337
• 49e Luo N, Zheng Z, Yu Z. Org. Lett. 2011; 13: 3384
• 49f Zheng Z, Chen J, Luo N, Yu Z, Han X. Organometallics 2006; 25: 5301
• 49g Zheng Z, Yu Z, Luo N, Han X. J. Org. Chem. 2006; 71: 9695
• 50a Alcázar J, Alonso JM, Bartolomé JM, Iturrino L, Matesanz E. Tetrahedron Lett. 2003; 44: 8983
• 50b Yoo E, Crall BM, Balakrishna R, Malladi SS, Fox LM, Hermanson AR, David SA. Org. Biomol. Chem. 2013; 11: 6526
• 50c De Schutter JW, Shaw J, Lin Y.-S, Tsantrizos YS. Bioorg. Med. Chem. 2012; 20: 5583
• 50d Londregan AT, Jennings S, Wei L. Org. Lett. 2010; 12: 5254
• 50e Yin J, Xiang B, Huffman MA, Raab CE, Davies IW. J. Org. Chem. 2007; 72: 4554
• 50f Manley PJ, Bilodeau MT. Org. Lett. 2002; 4: 3127
• 50g Chen X, Li X, Qu Z, Ke D, Qu L, Duan L, Mai W, Yuan J, Chen J, Zhao Y. Adv. Synth. Catal. 2014; 356: 1979
• 50h Couturier M, Caron L, Tumidajski S, Jones K, White TD. Org. Lett. 2006; 8: 1929
• 50i Londregan AT, Jennings S, Wei L. Org. Lett. 2011; 13: 1840
• 50j Medley JW, Movassaghi M. J. Org. Chem. 2008; 74: 1341
• 50k Kokatla HP, Yoo E, Salunke DB, Sil D, Ng CF, Balakrishna R, Malladi SS, Fox LM, David SA. Org. Biomol. Chem. 2013; 11: 1179
• 50l Ichihara Y, Fujimura R, Tsuneki H, Wada T, Okamoto K, Gouda H, Hirono S, Sugimoto K, Matsuya Y, Sasaoka T, Toyooka N. Eur. J. Med. Chem. 2013; 62: 649
• 50m Farrell RP, Silva Elipe MV, Bartberger MD, Tedrow JS, Vounatsos F. Org. Lett. 2013; 15: 168
• 50n Eskildsen J, Vedsø P, Begtrup M. Synthesis 2001; 1053
• 51 Abramovitch RA, Singer GM. J. Am. Chem. Soc. 1969; 91: 5672
• 52 Kellogg RM, Van Bergen TJ. J. Org. Chem. 1971; 36: 1705
• 53 Andersson H, Olsson R, Almqvist F. Org. Biomol. Chem. 2011; 9: 337
• 54 Andersson H, Sainte-Luce Banchelin T, Das S, Olsson R, Almqvist F. Chem. Commun. 2010; 46: 3384
• 55 Zhang S, Liao L.-Y, Zhang F, Duan X.-F. J. Org. Chem. 2013; 78: 2720
• 56 Hussain M, Banchelin TS.-L, Andersson H, Olsson R, Almqvist F. Org. Lett. 2013; 15: 54
• 57 Larionov OV, Stephens D, Mfuh A, Chavez G. Org. Lett. 2014; 16: 864
• 58 Araki Y, Kobayashi K, Yonemoto M, Kondo Y. Org. Biomol. Chem. 2011; 9: 78
• 59a Campeau L.-C, Schipper DJ, Fagnou K. J. Am. Chem. Soc. 2008; 130: 3266
• 59b Campeau L.-C, Bertrand-Laperle M, Leclerc J.-P, Villemure E, Gorelsky S, Fagnou K. J. Am. Chem. Soc. 2008; 130: 3276
• 59c Campeau L.-C, Rousseaux S, Fagnou K. J. Am. Chem. Soc. 2005; 127: 18020
• 59d Huestis MP, Fagnou K. Org. Lett. 2009; 11: 1357
• 59e Schipper DJ, Campeau L.-C, Fagnou K. Tetrahedron 2009; 65: 3155
• 59f Sun H.-Y, Gorelsky SI, Stuart DR, Campeau L.-C, Fagnou K. J. Org. Chem. 2010; 75: 8180
• 59g Tan Y, Barrios-Landeros F, Hartwig JF. J. Am. Chem. Soc. 2012; 134: 3683
• 60 Xiao B, Liu Z.-J, Liu L, Fu Y. J. Am. Chem. Soc. 2013; 135: 616
• 61 Wu Z, Song H, Cui X, Pi C, Du W, Wu Y. Org. Lett. 2013; 15: 1270
• 62 Cho SH, Hwang SJ, Chang S. J. Am. Chem. Soc. 2008; 130: 9254
• 63a Liu W, Li Y, Xu B, Kuang C. Org. Lett. 2013; 15: 2342
• 63b Liu W, Li Y, Wang Y, Kuang C. Org. Lett. 2013; 15: 4682
• 64 Wu Z, Pi C, Cui X, Bai J, Wu Y. Adv. Synth. Catal. 2013; 355: 1971
• 65 Li G, Jia C, Sun K. Org. Lett. 2013; 15: 5198
• 66 Zhu C, Yi M, Wei D, Chen X, Wu Y, Cui X. Org. Lett. 2014; 16: 1840
• 67 Kanyiva KS, Nakao Y, Hiyama T. Angew. Chem. Int. Ed. 2007; 46: 8872
• 68 Chen X, Zhu C, Cui X, Wu Y. Chem. Commun. 2013; 49: 6900
• 69 Shibata T, Matsuo Y. Adv. Synth. Catal. 2014; 356: 1516
• 70 Hwang H, Kim J, Jeong J, Chang S. J. Am. Chem. Soc. 2014; 136: 10770
• 71 Jeong J, Patel P, Hwang H, Chang S. Org. Lett. 2014; 16: 4598
• 72a Heaney F, Lawless E, Mahon M, McArdle P, Cunningham D. Org. Biomol. Chem. 2006; 4: 2408
• 72b Holt J, Fiksdahl A. J. Heterocycl. Chem. 2007; 44: 375
• 72c Raminelli C, Liu Z, Larock RC. J. Org. Chem. 2006; 71: 4689
• 72d Shaibu BS, Kawade RK, Liu R.-S. Org. Biomol. Chem. 2012; 10: 6834
• 72e Loska R, Mąkosza M. Mendeleev Commun. 2006; 16: 161
• 72f Loska R, Mąkosza M. Chem. Eur. J. 2008; 14: 2577
• 72g Loska R, Szachowicz K, Szydlik D. Org. Lett. 2013; 15: 5706