Gold-Catalyzed Synthesis of 2-Substituted Azepanes: Strategic Use of Soft Gold(I) and Hard Gold(III) Catalysts

Abstract

Strategic use of both soft gold(I) and hard gold(III) catalysts provides azepanes from propargylic alcohols in one pot. Thus, propargylic alcohols in the presence of soft gold(I) catalyst (Ph₃PAuNTf₂) undergo a Meyer–Schuster rearrangement to give α,β-unsaturated ketones, which in turn undergo a gold(III) (AuBr₃)-catalyzed aza-Michael addition to afford azepanes bearing a carbonyl group.

Key words

soft gold(I) catalyst - hard gold(III) catalyst - azepanes - Meyer–Schuster rearrangement - aza-Michael addition

• References and Notes

• 1 Vaquero JJ, Cuadro AM, Herradón B. Modern Heterocyclic Chemistry. Alvarez-Builla J, Vaquero J, Barluenga J. Wiley-VCH Verlag GmbH; Weinheim: 2011. 1st ed., 1865

For isolation and structure of actinophyllic acid, see:
• 2a Carroll AR, Hyde E, Smith J, Quinn RJ, Guymer G, Forster PI. J. Org. Chem. 2005; 70: 1096
• 2b Taniguchi T, Martin CL, Monde K, Nakanishi K, Berova N, Overman LE. J. Nat. Prod. 2009; 72: 430

For the synthesis of actinophyllic acid, see:
• 2c Granger BA, Jewett IT, Butler JD, Martin SF. Tetrahedron 2014; 70: 4094
• 2d Mortimer D, Whiting M, Harrity JP. A, Jones S, Coldham I. Tetrahedron Lett. 2014; 55: 1255
• 2e Granger BA, Jewett IT, Butler JD, Hua B, Knezevic CE, Parkinson EI, Hergenrother PJ, Martin SF. J. Am. Chem. Soc. 2013; 135: 12984
• 2f Galicia IZ, Maldonado LA. Tetrahedron Lett. 2013; 54: 2180
• 2g Zaimoku H, Taniguchi T, Ishibashi H. Org. Lett. 2012; 14: 1656
• 2h Martin CL, Overman LE, Rohde JM. J. Am. Chem. Soc. 2010; 132: 4894
• 2i Vaswani RG, Day JJ, Wood JL. Org. Lett. 2009; 11: 4532
• 2j Martin CL, Overman LE, Rohde JM. J. Am. Chem. Soc. 2008; 130: 7568

For isolation of arboflorine, see:
• 3a Lim K.-H, Hiraku O, Komiyama K, Koyano T, Hayashi M, Kam T.-S. J. Nat. Prod. 2007; 70: 1302
• 3b Lim K.-H, Kam T.-S. Org. Lett. 2006; 8: 1733

For synthesis of arboflorine, see:
• 3c Leal RA, Beaudry DR, Alzghari SK, Sarpong R. Org. Lett. 2012; 14: 5350
• 3d Du Y, Huang H.-Y, Liu H, Ruan Y.-P, Huang P.-Q. Synlett 2011; 565

For isolation and structure of balanol, see:
• 4a Ohshima S, Yanagisawa M, Katoh A, Fujii T, Sano T, Matsukuma S, Furumai T, Fujiu M, Watanabe K, Yokose K, Arisawa M, Okuda T. J. Antibiot. 1994; 47: 639
• 4b Kulanthaivel P, Hallock YF, Boros C, Hamilton SM, Janzen WP, Ballas LM, Loomis CR, Jiang JB, Katz B, Steiner JR, Clardy J. J. Am. Chem. Soc. 1993; 115: 6452

For the synthesis of balanol, see:
• 4c Fürstner A, Thiel OR. J. Org. Chem. 2000; 65: 1738
• 4d Miyabe H, Torieda M, Kiguchi T, Naito T. Synlett 1997; 580
• 4e Miyabe H, Torieda M, Inoue K, Tajiri K, Kiguchi T, Naito T. J. Org. Chem. 1998; 63: 4397
• 4f Lampe JW, Hughes PF, Biggers CK, Smith SH, Hu H. J. Org. Chem. 1996; 61: 4572
• 4g Nicolaou KC, Bunnage ME, Koide K. J. Am. Chem. Soc. 1994; 116: 8402
• 4h Lampe JW, Hughes PF, Biggers CK, Smith SH, Hu H. J. Org. Chem. 1994; 59: 5147
• 4i Nicolaou KC, Koide K, Bunnage ME. Chem. Eur. J. 1995; 1: 454
• 5 Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845

For the details of enthalpic and entropic factors, see:
• 6a Casadei MA, Galli C, Mandolini L. J. Am. Chem. Soc. 1984; 106: 1051
• 6b Galli C, Illuminati G, Mandolini L, Tamborra P. J. Am. Chem. Soc. 1977; 99: 2591

For ring-closing metathesis followed by hydrogenation, see:
• 7a Dragutan I, Dragutan V, Mitan C, Vosloo HC. M, Delaude L, Demonceau A. Beilstein J. Org. Chem. 2011; 7: 699
• 7b Wang H, Matsuhashi H, Doan BD, Goodman SN, Ouyang X, Clark WM. Jr. Tetrahedron 2009; 65: 6291
• 7c Roy SP, Chattopadhyay SK. Tetrahedron Lett. 2008; 49: 5498
• 7d Chang M.-Y, Kung Y.-H, Ma C.-C, Chen S.-T. Tetrahedron 2007; 63: 1339
• 7e Laventine DM, Jenkins PR, Cullis PM. Tetrahedron Lett. 2005; 46: 2295
• 7f Li H, Blériot Y, Chantereau C, Mallet J.-M, Sollogoub M, Zhang Y, Rodríguez-García E, Vogel P, Jiménez-Barbero J, Sinaÿ P. Org. Biomol. Chem. 2004; 2: 1492

For ring expansion reaction of cyclic compounds, see:
• 8a René O, Stepek IA, Gobbi A, Fauber BP, Gaines S. J. Org. Chem. 2015; 80: 10218
• 8b Nortcliffe A, Moody CJ. Bioorg. Med. Chem. 2015; 23: 2730
• 8c Zhou J, Yeung Y.-Y. Org. Lett. 2014; 16: 2134
• 8d Wishka DG, Bédard M, Brighty KE, Buzon RA, Farley KA, Fichtner MW, Kauffman GS, Kooistra J, Lewis JG, O’Dowd H, Samardjiev IJ, Samas B, Yalamanchi G, Noe MC. J. Org. Chem. 2011; 76: 1937
• 8e Chong H.-S, Ganguly B, Broker GA, Rogers RD, Brechbiel MW. J. Chem. Soc., Perkin Trans. 1 2002; 2080

For multisequences of carbohydrates, see:
• 9a Zhao W.-B, Nakagawa S, Kato A, Adachi I, Jia Y.-M, Hu X.-G, Fleet GW. J, Wilson FX, Horne G, Yoshihara A, Izumori K, Yu C.-Y. J. Org. Chem. 2013; 78: 3208
• 9b Oña N, Romero-Carrasco A, Pino-González MS. Tetrahedron: Asymmetry 2013; 24: 156
• 9c Jadhav VH, Bande OP, Puranik VG, Dhavale DD. Tetrahedron: Asymmetry 2010; 21: 163
• 9d Estévez AM, Soengas RG, Otero JM, Estévez JC, Nash RJ, Estévez RJ. Tetrahedron: Asymmetry 2010; 21: 21
• 9e Li H, Liu T, Zhang Y, Favre S, Bello C, Vogel P, Butters TD, Oikonomakos NG, Marrot J, Blériot Y. ChemBioChem 2008; 9: 253
• 9f Dolhem F, Tahli FA, Lièvre C, Demailly G. Eur. J. Org. Chem. 2005; 5019
• 9g Dhavale DD, Markad SD, Karanjule NS, PrakashaReddy J. J. Org. Chem. 2004; 69: 4760
• 9h Andersen SM, Ekhart C, Lundt I, Stütz AE. Carbohydr. Res. 2000; 326: 22

For multisequences of other compounds, see:
• 10a Das SN, Chowdhury A, Tripathi N, Jana PK, Mandal SB. J. Org. Chem. 2015; 80: 1136
• 10b González-Castro MA, Poole DL, Estévez JC, Fleet GW. J, Estévez RJ. Tetrahedron: Asymmetry 2015; 26: 320
• 10c Goudedranche S, Pierrot D, Constantieux T, Bonne D, Rodriguez J. Chem. Commun. 2014; 50: 15605
• 10d Kazi B, Kiss L, Forró E, Fülöp F. Tetrahedron Lett. 2010; 51: 82
• 10e Lee SJ, Beak P. J. Am. Chem. Soc. 2006; 128: 2178
• 10f Gauzy L, LeMerrer Y, Depezay J.-C, Clerc F, Mignani S. Tetrahedron Lett. 1999; 40: 6005

There are some examples of construction of azepane via aza-Michael addition of conformationally constrained substrates in the total synthesis of natural products. For selected reports, see:
• 11a Li W.-DZ, Duo W.-G, Zhuang C.-H. Org. Lett. 2011; 13: 3538
• 11b Shah U, Chackalamannil S, Ganguly AK, Chelliah M, Kolotuchin S, Buevich A, McPhail A. J. Am. Chem. Soc. 2006; 128: 12654

For reviews of aza-Michael addition, see:
• 11c Amara Z, Caron J, Joseph D. Nat. Prod. Rep. 2013; 30: 1211
• 11d Enders D, Wang C, Liebich JX. Chem. Eur. J. 2009; 15: 11058
• 11e Xu L.-W, Xia C.-G. Eur. J. Org. Chem. 2005; 633

For selected example of intramolecular aza-Michael addition, see:
• 11f Cheng S, Yu S. Org. Biomol. Chem. 2014; 12: 8607

For examples of synthesis of azepane from highly flexible linear compounds, see:
• 12a Cini E, Bifulco G, Menchi G, Rodriquez M, Taddei M. Eur. J. Org. Chem. 2012; 2133
• 12b Ito H, Harada T, Ohmiya H, Sawamura M. Beilstein J. Org. Chem. 2011; 7: 951
• 12c Denmark SE, Xie M. J. Org. Chem. 2007; 72: 7050

For Wittig reaction, see:
• 13a Maryanoff BE, Reitz AB. Chem. Rev. 1989; 89: 863
• 13b Wittig G, Schöllkopf U. Chem. Ber. 1958; 91: 61

For Horner–Wadsworth–Emmons reaction, see:
• 14a Bisceglia JÁ, Orelli LR. Curr. Org. Chem. 2015; 19: 744
• 14b Wadsworth WS. Jr, Emmons WD. J. Am. Chem. Soc. 1961; 83: 1733

For Peterson reaction, see:
• 15a Barrett AG. M, Hill JM, Wallace EM, Flygare JA. Synlett 1991; 764
• 15b Ager DJ. Synthesis 1984; 384
• 15c Peterson DJ. J. Org. Chem. 1968; 33: 780
• 16 For aldol condensation, see: Machajewski TD, Wong C.-H. Angew. Chem. Int. Ed. 2000; 39: 1352

For reviews on Meyer–Schuster rearrangement, see:
• 17a Cadierno V, Crochet P, García-Garrido SE, Gimeno J. Dalton Trans. 2010; 39: 4015
• 17b Engel DA, Dudley GB. Org. Biomol. Chem. 2009; 7: 4149

For the first report on Meyer–Schuster rearrangement, see:
• 17c Meyer KH, Schuster K. Chem. Ber. 1922; 55: 819
• 18 Morita N, Yasuda A, Shibata M, Ban S, Hashimoto Y, Okamoto I, Tamura O. Org. Lett. 2015; 17: 2668
• 19 Morita N, Tsunokake T, Narikiyo Y, Harada M, Tachibana T, Saito Y, Ban S, Hashimoto Y, Okamoto I, Tamura O. Tetrahedron Lett. 2015; 56: 6269

For recent examples of gold-catalyzed Meyer–Schuster rearrangement of propargylic alcohols, see:
• 20a Mou X.-Q, Xu Z.-L, Wang S.-H, Zhu D.-Y, Wang J, Bao W, Zhou S.-J, Yang C, Zhang D. Chem. Commun. 2015; 51: 12064
• 20b An J.-H, Yun H, Shin S, Shin S. Adv. Synth . Catal. 2014; 356: 3749
• 20c Kim SM, Lee D, Hong SH. Org. Lett. 2014; 16: 6168
• 20d Hansmann MM, Hashmi AS. K, Lautens M. Org. Lett. 2013; 15: 3226
• 20e Pennell MN, Turner PG, Sheppard TD. Chem.−Eur. J. 2012; 18: 4748
• 20f Pennell MN, Unthank MG, Turner P, Sheppard TD. J. Org. Chem. 2011; 76: 1479
• 20g Rieder CJ, Winberg KJ, West FG. J. Org. Chem. 2011; 76: 50
• 20h Ramón RS, Gaillard S, Slawin AM. Z, Porta A, D’Alfonso A, Zanoni G, Nolan SP. Organometallics 2010; 29: 3665
• 20i Ramón RS, Marion N, Nolan SP. Tetrahedron 2009; 65: 1767
• 20j Egi M, Yamaguchi Y, Fujiwara N, Akai S. Org. Lett. 2008; 10: 1867
• 20k Lopez SS, Engel DA, Dudley GB. Synlett 2007; 949
• 20l Lee SI, Baek JY, Sim SH, Chung YK. Synthesis 2007; 2107
• 20m Engel DA, Dudley GB. Org. Lett. 2006; 8: 4027
• 21 We chose propargylic alcohol protected by sulfonyl group (Ts) in this reaction because the synthesis of piperidines was achieved from propargylic alcohols protected by sulfonyl (Ms, Ts and Ns) and tert-butoxycarbonyl groups (Boc) in our previous work (see ref. 19). The reaction of substrates protected by the sulfonyl group (Ms, Ts and Ns) proceeded smoothly for 1d to afford the corresponding piperidines, whereas the reaction of substrate protected by tert-butoxycarbonyl group (Boc) proceeded with longer reaction periods of 4 d, to furnish the corresponding piperidine.
• 22 Procedure for the Synthesis of 1-Phenyl-2-(1-tosylazepan-2-yl)ethan-1-one (9a): [Ph₃PAuNTf₂]₂PhMe (2.2 mg, 1.0 mol%) was added at r.t. to a solution of propargylic alcohol 7a (50 mg, 0.13 mmol) and MeOH (5.7 μL, 0.14 mmol) in toluene (5 mL). After complete consumption of propargylic alcohol 7a (the reaction was monitored by TLC; 1 d), AuBr₃ (3.0 mg, 5.0 mol%) was added to the reaction solution at r.t. After stirring for 1 d, the solvent was removed in vacuo and the crude product was subjected to column chromatography on silica gel (hexane–Et₂O, 1:1) to give 1-phenyl-2-(1-tosylazepan-2-yl)ethan-1-one (9a; 43 mg, 86%) as a colorless oil. IR (KBr): 2928, 2856, 1682, 1597, 1331, 1152, 1090, 949, 880 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.92 (dd, J = 6.9, 1.5 Hz, 2 H), 7.74 (dd, J = 8.4, 1.8 Hz, 2 H), 7.54–7.60 (m, 1 H), 7.43–7.49 (m, 2 H), 7.24 (d, J = 7.5 Hz, 2 H), 4.30–4.40 (m, 1 H), 3.92 (dt, J = 15.0, 3.6 Hz, 1 H), 3.38 (dd, J = 15.3, 3.6 Hz, 1 H), 3.09 (ddd, J = 15.3, 11.1, 2.7 Hz, 1 H), 3.00 (dd, J = 15.3, 9.6 Hz, 1 H), 2.37 (s, 3 H), 2.04–2.14 (m, 1 H), 1.47–1.69 (m, 4 H), 1.15–1.39 (m, 2 H), 0.95–1.07 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 198.0, 143.0, 138.5, 136.5, 133.2, 129.6, 128.6, 128.2, 127.2, 54.4, 45.1, 43.9, 34.5, 29.2, 29.1, 24.4, 21.4. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₁H₂₆NO₃S: 372.1628; found: 372.1622.
• 23a Jung HH, Floreancig PE. J. Org. Chem. 2007; 72: 7359
• 23b Jung HH, Floreancig PE. Org. Lett. 2006; 8: 1949
• 24 Procedure for the Synthesis of 1-(4-Methoxyphenyl)-2-(1-tosylazepan-2-yl)ethan-1-one (9b): [Ph₃PAuNTf₂]₂PhMe (1.6 mg, 1.0 mol%) was added at r.t. to a solution of propargylic alcohol 7b (40 mg, 0.10 mmol) and MeOH (4.1 μL, 0.09 mmol) in toluene (5 mL). After stirring for 1 d at r.t., AuBr₃ (2.2 mg, 5.0 mol%) was added to the reaction solution at r.t. After stirring for 1 d at 60 °C, the solvent was removed in vacuo and the crude product was subjected to column chromatography on silica gel (hexane–Et₂O, 1:1) to give 1-(4-methoxyphenyl)-2-(1-tosylazepan-2-yl)ethan-1-one (9b; 30 mg, 75%) as a colorless oil. IR (KBr): 2930, 2856, 1672, 1601, 1329, 1261, 1151, 1090, 816 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.92 (dd, J = 8.7, 1.8 Hz, 2 H), 7.75 (d, J = 8.1 Hz, 2 H), 7.25 (d, J = 8.1 Hz, 2 H), 6.94 (dd, J = 8.7, 1.8 Hz, 2 H), 4.28–4.38 (m, 1 H), 3.80–3.95 (m, 1 H), 3.88 (s, 3 H), 3.36 (dd, J = 15.0, 3.6 Hz, 1 H), 3.08 (ddd, J = 15.3, 10.8, 2.1 Hz, 1 H), 2.79 (dd, J = 15.0, 9.9 Hz, 1 H), 2.39 (s, 3 H), 2.02–2.12 (m, 1 H), 1.45–1.72 (m, 4 H), 1.12–1.39 (m, 2 H), 0.93–1.04 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 196.5, 163.6, 143.0, 138.6, 130.6, 129.7, 129.6, 127.2, 113.8, 55.5, 54.7, 44.9, 43.8, 34.4, 29.2, 29.0, 24.3, 21.5. HRMS (FAB): m/z [M + H]⁺ calcd for C₂₂H₂₈NO₄S: 402.1734; found: 402.1747.