Microwave-Assisted Copper-Catalyzed Coupling of Bromoalkynes and Sulfonamides: Rapid Synthesis of N-Sulfonyl Ynamides

Abstract

The synergistic effect of an alcohol solvent and microwave irradiation dramatically increased the C–N coupling rate, enabling the rapid synthesis of N-sulfonyl ynamides in ten minutes. The optimal catalyst, ligand, and solvent combination was investigated, and various bromoalkynes and sulfonamides were shown to be tolerated under these conditions.

Key words

C–N coupling - ynamides - sulfonamides - microwave irradiation - solvent effect

Publication History

Received: 25 September 2023

Accepted after revision: 23 October 2023

Accepted Manuscript online:
23 October 2023

Article published online:
22 November 2023

• References and Notes


For selected examples, see:
• 1a Das JP, Chechik H, Marek I. Nat. Chem. 2009; 1: 128
• 1b Romain E, Fopp C, Chemla F, Ferreira F, Jackowski O, Oestreich M, Perez-Luna A. Angew. Chem. Int. Ed. 2014; 53: 11333
• 1c Zeng X, Li J, Ng CK, Hammond GB, Xu B. Angew. Chem. Int. Ed. 2018; 57: 2924
• 1d Zhou B, Li L, Zhu X.-Q, Yan J.-Z, Guo Y.-L, Ye L.-W. Angew. Chem. Int. Ed. 2017; 56: 4015
• 1e Huang B, Zeng L, Shen Y, Cui S. Angew. Chem. Int. Ed. 2017; 56: 4565
• 2 Rodríguez D, Castedo L, Saá C. Synlett 2004; 783
• 3a Huang J, Xiong H, Hsung RP, Rameshkumar C, Mulder JA, Grebe TP. Org. Lett. 2002; 4: 2417
• 3b Pan F, Shu C, Ye L.-W. Org. Biomol. Chem. 2016; 14: 9456
• 4a Witulski B, Gößmann M. Synlett 2000; 1793
• 4b Shen L, Hsung RP. Tetrahedron Lett. 2003; 44: 9353
• 5a Zificsak CA, Mulder JA, Hsung RP, Rameshkumar C, Wei LL. Tetrahedron 2001; 57: 7575
• 5b DeKorver KA, Li H, Lohse AG, Hayashi R, Lu Z, Zhang Y, Hsung RP. Chem. Rev. 2010; 110: 5064
• 5c Evano G, Coste A, Jouvin K. Angew. Chem. Int. Ed. 2010; 49: 2840
• 5d Wang X.-N, Yeom H.-S, Fang L.-C, He S, Ma Z.-X, Kedrowski BL, Hsung RP. Acc. Chem. Res. 2014; 47: 560
• 5e Cook AM, Wolf C. Tetrahedron Lett. 2015; 56: 2377
• 5f Evano G, Michelet B, Zhang C. C. R. Chim. 2017; 20: 648
• 5g Dodd RH, Cariou K. Chem. Eur. J. 2018; 24: 2297
• 6 Janousek Z, Collard J, Viehe HG. Angew. Chem. Int. Ed. 1972; 11: 917
• 7a Brückner D. Tetrahedron 2006; 62: 3809
• 7b Rainier JD, Imbriglio JE. Org. Lett. 1999; 1: 2037
• 7c Rodríguez D, Fernanda Martínez-Esperón M, Castedo L, Saá C. Synlett 2007; 1963
• 7d Tracey MR, Zhang Y, Frederick MO, Mulder JA, Hsung RP. Org. Lett. 2004; 6: 2209
• 7e Wei L.-L, Mulder JA, Xiong H, Zificsak CA, Douglas CJ, Hsung RP. Tetrahedron 2001; 57: 459

For reviews, see:
• 8a Hu Y.-C, Zhao Y, Wan B, Chen Q.-A. Chem. Soc. Rev. 2021; 50: 2582
• 8b Chen Y.-B, Qian P.-C, Ye L.-W. Chem. Soc. Rev. 2020; 49: 8897
• 8c Hong F.-L, Ye L.-W. Acc. Chem. Res. 2020; 53: 2003
• 8d Lynch CC, Sripada A, Wolf C. Chem. Soc. Rev. 2020; 49: 8543 ; see also Ref. 5d
• 9a Zhang Y, Hsung RP, Tracey MR, Kurtz KC. M, Vera EL. Org. Lett. 2004; 6: 1151
• 9b Dooleweerdt K, Birkedal H, Ruhland T, Skrydstrup T. J. Org. Chem. 2008; 73: 9447
• 9c Zhang X, Zhang Y, Huang J, Hsung RP, Kurtz KC. M, Oppenheimer J, Petersen ME, Sagamanova IK, Tracey MR. T. J. Org. Chem. 2006; 71: 4170
• 9d Dunetz JR, Danheiser RL. Org. Lett. 2003; 5: 4011
• 9e Yao B, Liang Z, Niu T, Zhang Y. J. Org. Chem. 2009; 74: 4630
• 10 Frederick MO, Mulder JA, Tracey MR, Hsung RP, Huang J, Kurtz KC. M, Shen L, Christopher JD. J. Am. Chem. Soc. 2003; 125: 2368
• 11 Zheng X, Tu Y, Zhang Z, You C, Wu J, Ye Z, Zhao J. J. Org. Chem. 2019; 84: 4458
• 12a Hamada T, Ye X, Stahl SS. J. Am. Chem. Soc. 2008; 130: 833
• 12b Jin X, Yamaguchi K, Mizuno N. Chem. Commun. 2012; 48: 4974
• 12c Wang L, Huang H, Priebbenow DL, Pan F.-F, Bolm C. Angew. Chem. Int. Ed. 2013; 52: 3478
• 12d Laroche C, Li J, Freyer MW, Kerwin SM. J. Org. Chem. 2008; 73: 6462
• 13a Jia W, Jiao N. Org. Lett. 2010; 12: 2000
• 13b Priebbenow DL, Becker P, Bolm C. Org. Lett. 2013; 15: 6155
• 14a Jouvin K, Heimburger J, Evano G. Chem. Sci. 2012; 3: 756
• 14b Theunissen C, Lecomte M, Jouvin K, Laouiti A, Guissart C, Heimburger J, Loire E, Evano G. Synthesis 2014; 46: 1157
• 15 Jouvin K, Couty F, Evano G. Org. Lett. 2010; 12: 3272
• 16 Sueda T, Oshima A, Teno N. Org. Lett. 2011; 13: 3996
• 17 Waldecker B, Kraft F, Golz C, Alcarazo M. Angew. Chem. Int. Ed. 2018; 57: 12538
• 18a Witulski B, Stengel T. Angew. Chem. Int. Ed. 1998; 37: 489
• 18b Murch P, Williamson BL, Stang PJ. Synthesis 1994; 1994: 1255
• 18c Feldman KS, Bruendl MM, Schildknegt K, Bohnstedt AC. J. Org. Chem. 1996; 61: 5440
• 18d Zhdankin VV, Stang PJ. Tetrahedron 1998; 54: 10927 (19)
• 18e Aubineau T, Cossy J. Chem. Commun. 2013; 49: 3303
• 18f Tokimizu Y, Oishi S, Fujii N, Ohno H. Org. Lett. 2014; 16: 3138
• 18g Takai R, Shimbo D, Tada N, Itoh A. J. Org. Chem. 2021; 86: 4699
• 19a Coste A, Karthikeyan G, Couty F, Evano G. Angew. Chem. Int. Ed. 2009; 48: 4381
• 19b Jouvin K, Coste A, Bayle A, Legrand F, Karthikeyan G, Tadiparthi K, Evano G. Organometallics 2012; 31: 7933
• 19c Yang Y, Zhang X, Liang Y. Tetrahedron Lett. 2012; 53: 6557
• 19d Yu Y, Zheng X, Wang H, Zhao J. Org. Lett. 2018; 20: 280
• 19e Mansfield SJ, Campbell CD, Jones MW, Anderson EA. Chem. Commun. 2015; 51: 3316
• 19f Xue J, Luo M.-T, Wen Y.-L, Ye M, Liu L.-X, Chen Z.-W. Synthesis 2014; 46: 3191
• 20a Yao M.-L, Reddy MS, Yong L, Walfish I, Blevins DW, Kabalka GW. Org. Lett. 2010; 12: 700
• 20b Okutani M, Mori Y. J. Org. Chem. 2009; 74: 442
• 20c Huang X, Chen H, Huang Z, Xu Y, Li F, Ma X, Chen Y. J. Org. Chem. 2019; 84: 15283
• 20d Rajbongshi K.-K, Hazarika D, Phujan P. Tetrahedron. 2016; 72: 4151
• 20e Shi W, Guan Z, Cai P, Chen H. J. Catal. 2017; 353: 199
• 20f Li M, Li Y, Zhao B, Liang F, Jin L.-Y. RSC Adv. 2014; 4: 30046
• 20g Fukudome Y, Naito H, Hata T, Urabe H. J. Am. Chem. Soc. 2008; 130: 1820
• 20h Jiang X.-W, Rawat M, Wulff WD. J. Am. Chem. Soc. 2004; 126: 5970
• 20i Allen A, Villeneuve K, Cockburn N, Fatila E, Riddell N, Tam W. Eur. J. Org. Chem. 2008; 4178
• 20j Song L, Tian X, Rudolph M, Rominger F, Hashmi AS. K. Chem. Commun. 2019; 55: 9007
• 20k Wantanabe K, Mino T, Ishikawa E, Okano M, Ikematsu T, Yoshida Y, Sakamoto M, Satp K, Yoshida K. Eur. J. Org. Chem. 2017; 2359
• 20l Kesharwani T, Kornman C, Tonnaer A, Hayes A, Kim S, Dahal N, Romero R, Royappa A. Tetrahedron. 2018; 74: 2973
• 21 Hong SJ, Yoon CJ, Lim HN, Yeom H.-S. Eur. J. Org. Chem. 2021; 2021: 5609
• 22 Kim S, Lim SY, Kwak K, Lim HN, Yeom H.-S. Synthesis 2002; 54: 5451
• 23 N,4-Dimethyl-N-(phenylethynyl)benzenesulfonamide (3aa); Typical Procedure Ethynylbenzene (1a; 0.28 mmol), sulfonamide 2a (0.42 mmol, 1.5 equiv), CuSO₄·5 H₂O (0.028 mmol, 10 mol%), DMEDA (0.056 mmol, 20 mol%), and K₂CO₃ (0.70 mmol, 2.5 equiv) was suspended in anhyd MeOH (2.8 mL) in a microwave reactor vial. The vial was sealed with a cap, and the mixture was subjected to microwave irradiation at 90 °C for 10 min, then cooled. The precipitate was collected by filtration and washed with CH₂Cl₂. The filtrate was concentrated and purified by column chromatography (silica gel) to give a white solid; yield: 89%; mp 85.0 °C; R_f = 0.2 (EtOAc–hexane, 1:10). IR (neat): 2229, 1359, 1160, 952, 755, 674 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.84 (d, J = 8.1 Hz, 2 H), 7.39–7.34 (m, 4 H), 7.31–7.27 (m, 3 H), 3.15 (s, 3 H), 2.46 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 144.8, 133.2, 131.4, 129.8, 128.3, 127.9, 122.7, 84.0, 69.0, 39.3, 21.7. HRMS (EI+): m/z [M⁺] calcd for C₁₆H₁₅NO₂S: 285.0818; found: 285.0820.