Asymmetric Chlorination of 4-Substituted Pyrazolones Catalyzed by Chiral Copper Complexes

Abstract

A fast and highly enantioselective chlorination of 4-pyrazolones catalyzed by bis(oxazoline)–Cu(ClO₄)₂·6H₂O complexes has been developed. Under the optimized conditions, a series of pyrazolones bearing stereogenic chlorine-attached carbon centers were obtained in moderate to high yields (up to 98%) and with enantioselectivities of up to 98% ee.

Key words

asymmetric catalysis - copper catalysis - bisoxazolines - chlorination - pyrazolones

• References and Notes

• 1a Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N, Tada N. CNS Drug Rev. 2006; 12: 9
• 1b Kimata A, Nakagawa H, Ohyama R, Fukuuchi T, Ohta S, Suzuki T, Miyata N. J. Med. Chem. 2007; 50: 5053
• 1c Hadi V, Koh Y.-H, Sanchez TW, Barrios D, Neamati N, Jung KW. Bioorg. Med. Chem. Lett. 2010; 20: 6854
• 1d Zhou F, Liu Y.-L, Zhou J. Adv. Synth. Catal. 2010; 352: 1381
• 1e Fustero S, Sánchez-Rosellό M, Barrio P, Simόn-Fuentes A. Chem. Rev. 2011; 111: 6984
• 1f Hamama WS, El-Gohary HG, Kuhnert N, Zoorob HH. Curr. Org. Chem. 2012; 16: 373
• 1g Kumar V, Kaur K, Gupta GK, Sharma AK. Eur. J. Med. Chem. 2013; 69: 735
• 1h Kaya U, Mahajan S, Schöbel J.-H, Valkonen A, Rissanen K, Enders D. Synthesis 2016; 48: 4091
• 1i Ansari A, Ali A, Asif M. Shamsuzzaman New J. Chem. 2017; 41: 16
• 1j El Sayed MT, El-Sharief MA. M. S, Zarie ES, Morsy NM, Elsheakh AR, Voronkov A, Berishvili V, Hassan GS. Bioorg. Med. Chem. Lett. 2018; 28: 952

For reviews, see:
• 2a Chauhan P, Mahajan S, Enders D. Chem. Commun. 2015; 51: 12890
• 2b Liu S, Bao X, Wang B. Chem. Commun. 2018; 54: 11515

For selected examples, see:
• 3a Yang Z, Wang Z, Bai S, Liu X, Lin L, Feng X. Org. Lett. 2011; 13: 596
• 3b Wang Z, Yang Z, Chen D, Liu X, Lin L, Feng X. Angew. Chem. Int. Ed. 2011; 50: 4928
• 3c Wang Z, Chen Z, Bai S, Li W, Liu X, Lin L, Feng X. Angew. Chem. Int. Ed. 2012; 51: 2776
• 3d Chen Z.-P, Chen M.-W, Shi L, Yu C.-B, Zhou Y.-G. Chem. Sci. 2015; 6: 3415
• 3e Zhou H, Wei Z, Zhang J, Yang H, Xia C, Jiang G. Angew. Chem. Int. Ed. 2017; 56: 1077
• 3f Zhen J, Wang S.-B, Zheng C, You S.-L. Angew. Chem. Int. Ed. 2017; 56: 4540
• 3g Chen M.-Y, Xu Z, Chen L, Song T, Zheng Z.-J, Cao J, Cui Y.-M, Xu L.-W. ChemCatChem 2018; 10: 280
• 3h Xu J, Hu L, Hu H, Ge S, Liu X, Feng X. Org. Lett. 2019; 21: 1632
• 3i Lu J, Luo L.-S, Sha F, Li Q, Wu X.-Y. Chem. Commun. 2019; 55: 11603

For selected examples of enantioenriched pyrazolone derivatives, see:
• 4a Li F, Sun L, Teng Y.-O, Yu P, Zhao JC.-G, Ma J.-A. Chem. Eur. J. 2012; 18: 14255
• 4b Chen Q, Liang J.-Y, Wang S.-L, Wang D, Wang R. Chem. Commun. 2013; 49: 1657
• 4c Wang H, Wang Y, Song H, Zhou Z, Tang C. Eur. J. Org. Chem. 2013; 4844
• 4d Bao X, Wang B, Cui L, Zhu G, He Y, Qu J, Song Y. Org. Lett. 2015; 17: 5168
• 4e Bao X, Wei S, Zou L, Song Y, Qu J, Wang B. Tetrahedron: Asymmetry 2016; 27: 436
• 4f Yetra SR, Mondal S, Mukherjee S, Gonnade RG, Biju AT. Angew. Chem. Int. Ed. 2016; 55: 268
• 4g Xue F, Bao X.-Z, Zou L, Qu J, Wang B. Adv. Synth. Catal. 2016; 358: 3971
• 4h Mahajan S, Chauhan P, Kaya U, Deckers K, Rissanen K, Enders D. Chem. Commun. 2017; 53: 6633
• 4i Kaya U, Chauhan P, Mahajan S, Deckers K, Valkonen A, Rissanen K, Enders D. Angew. Chem. Int. Ed. 2017; 56: 15358
• 4j Chauhan P, Mahajan S, Kaya U, Peuronen A, Rissanen K, Enders D. J. Org. Chem. 2017; 82: 7050
• 4k Meninno S, Roselli A, Capobianco A, Overgaard J, Lattanzi A. Org. Lett. 2017; 19: 5030
• 4l Xia A.-B, Zhang X.-L, Tang C.-K, Feng K.-X, Du X.-H, Xu D.-Q. Org. Biomol. Chem. 2017; 15: 5709
• 4m Zhou J, Huang W.-J, Jiang G.-F. Org. Lett. 2018; 20: 1158
• 4n Bao X, Wei S, Qian X, Qu J, Wang B, Zou L, Ge G. Org. Lett. 2018; 20: 3394
• 4o Yang Z.-T, Yang W.-L, Chen L, Sun H, Deng W.-P. Adv. Synth. Catal. 2018; 360: 2049
• 4p Zhou Y, You Y, Wang Z.-H, Zhang X.-M, Xu X.-Y, Yuan W.-C. Eur. J. Org. Chem. 2019; 3112
• 4q Zhang J, Chan W.-L, Chen L, Ullah N, Lu Y. Org. Chem. Front. 2019; 6: 2210
• 4r Liu X.-L, Zuo X, Wang J.-X, Chang S.-Q, Wei Q.-D, Zhou Y. Org. Chem. Front. 2019; 6: 1485
• 4s Chu M.-M, Qi S.-S, Wang Y.-F, Wang B, Jiang Z.-H, Xu D.-Q, Xu Z.-Y. Org. Chem. Front. 2019; 6: 1977
• 4t Meninno S, Mazzanti A, Lattanzi A. Adv. Synth. Catal. 2019; 361: 79
• 4u Lin Y, Zhao B.-L, Du D.-M. J. Org. Chem. 2019; 84: 10209
• 4v Tan C.-Y, Lu H, Zhang J.-L, Liu J.-Y, Xu P.-F. J. Org. Chem. 2020; 85: 594
• 4w Xu X.-Y, He Y.-M, Zhou J.-Q, Li X.-J, Zhu B, Chang J.-B. J. Org. Chem. 2020; 85: 574
• 5 Bao X, Wei S, Zou L, He Y, Xue F, Qu J, Wang B. Chem. Commun. 2016; 52: 11426

For reviews, see:
• 6a Desimoni G, Faita G, Jørgensen K.-A. Chem. Rev. 2006; 106: 3561
• 6b Ollevier T. Catal. Sci. Technol. 2016; 6: 41
• 6c Wang L, Zhou J, Tang Y. Chin. J. Chem. 2018; 36: 1123
• 6d Itoh K, Sibi MP. Org. Biomol. Chem. 2018; 16: 5551
• 6e Babu SA, Krishnan K, Ujwaldev SM, Anilkumar G. Asian J. Org. Chem. 2018; 7: 1033
• 6f Rohit KR, Ujwaldev SM. Saranya S, Anilkumar G. Asian J. Org. Chem. 2018; 7: 2338

For selected examples, see:
• 7a Cheng H.-G, Lu L.-Q, Wang T, Yang Q.-Q, Liu X.-P, Li Y, Deng Q.-H, Chen J.-R, Xiao W.-J. Angew. Chem. Int. Ed. 2013; 52: 3250
• 7b Chu JC. K, Dalton DM, Rovis T. J. Am. Chem. Soc. 2015; 137: 4445
• 7c Chen W.-Q, Yang Q, Zhou T, Tian Q.-S, Zhang G.-Z. Org. Lett. 2015; 17: 5236
• 7d Lippur K, Kaabel S, Järving I, Rissanen K, Kanger T. J. Org. Chem. 2015; 80: 6336
• 7e Liu Q.-J, Wang L, Kang Q.-K, Zhang XP, Tang Y. Angew. Chem. Int. Ed. 2016; 55: 9220
• 7f Hari DP, Waser J. J. Am. Chem. Soc. 2017; 139: 8420
• 7g Lukamto DH, Gaunt MJ. J. Am. Chem. Soc. 2017; 139: 9160
• 7h Wu X, Zhou W, Wu H.-H, Zhang J. Chem. Commun. 2017; 53: 5661
• 7i Chen W, Bai J, Zhang G. Adv. Synth. Catal. 2017; 359: 1227
• 7j Liu F, Zhong J, Zhou Y, Gao Z, Walsh PJ, Wang X, Ma S, Hou S, Liu S, Wang M, Wang M, Bian Q. Chem. Eur. J. 2018; 24: 2059
• 7k Carreras J, Caballero A, Pérez PJ. Angew. Chem. Int. Ed. 2018; 57: 2334
• 7l Huang B.-B, Wu L, Liu R.-R, Xing L.-L, Liang R.-X, Jia Y.-X. Org. Chem. Front. 2018; 5: 929
• 7m Liu Q.-J, Zhu J, Song X.-Y, Wang L.-J, Wang SR, Tang Y. Angew. Chem. Int. Ed. 2018; 57: 3810
• 7n Fu Z, Deng N, Su S.-N, Li H, Li R.-Z, Zhang X, Liu J, Niu D. Angew. Chem. Int. Ed. 2018; 57: 15217
• 7o Fu N, Song L, Liu J, Shen Y, Siu J, Lin S. J. Am. Chem. Soc. 2019; 141: 14480
• 7p Han B, Li Y, Yu Y, Gong L. Nat. Commun. 2019; 10: 3804
• 7q Zhang W, Wu L, Chen P, Liu G. Angew. Chem. Int. Ed. 2019; 58: 6425
• 7r Liang X, Li R.-D, Wang X.-C. Angew. Chem. Int. Ed. 2019; 58: 13885
• 7s Wang C.-J, Sun J, Zhou W, Xue J, Ren B.-T, Zhang G.-Y, Mei Y.-L, Deng Q.-H. Org. Lett. 2019; 21: 7315
• 7t Lei G, Zhang H, Chen B, Xu M, Zhang G. Chem. Sci. 2020; 11: 1623
• 7u Yang C, Liu Z.-L, Dai D.-T, Li Q, Ma W.-W, Zhao M, Xu Y.-H. Org. Lett. 2020; 22: 1360
• 7v Guan Y, Attard J.-W, Mattson AE. Chem. Eur. J. 2020; 26: 1742
• 8a Shibata N, Kohno J, Takai K, Ishimaru T, Nakamura S, Toru T, Kanemasa S. Angew. Chem. Int. Ed. 2005; 44: 4204
• 8b Ishimaru T, Shibata N, Nagai J, Nakamura S, Toru T, Kanemasa S. J. Am. Chem. Soc. 2006; 128: 16488
• 8c Deng Q.-H, Wadepohl H, Gade LH. Chem. Eur. J. 2011; 17: 14922
• 8d Deng Q.-H, Wadepohl H, Gade LH. J. Am. Chem. Soc. 2012; 134: 10769
• 8e Deng Q.-H, Wadepohl H, Gade LH. J. Am. Chem. Soc. 2012; 134: 2946
• 8f Deng Q.-H, Bleith T, Wadepohl H, Gade LH. J. Am. Chem. Soc. 2013; 135: 5356
• 8g Deng Q.-H, Rettenmeier C, Wadepohl H, Gade LH. Chem. Eur. J. 2014; 20: 93
• 8h Ding W, Lu L.-Q, Zhou Q.-Q, Wei Y, Chen J.-R, Xiao W.-J. J. Am. Chem. Soc. 2017; 139: 63
• 8i Qiu J.-S, Wang Y.-F, Qi G.-R, Karmaker P.-G, Yin H.-Q, Chen F.-X. Chem. Eur. J. 2017; 23: 1775
• 9a Wang Y, Wang H, Jiang Y, Zhang C, Shao J, Xu D. Green Chem. 2017; 19: 1674
• 9b Wang H, Wang Y, Zhang C, Jiang Y, Chu M, Li Z, Du X, Xu D. Org. Biomol. Chem. 2017; 15: 4191
• 9c Wang Y.-F, Shao J.-J, Wang B, Chu M.-M, Qi S.-S, Du X.-H, Xu D.-Q. Adv. Synth. Catal. 2018; 360: 2285
• 9d Wang B, Wang Y, Jiang Y, Chu M, Qi S, Ju W, Xu D. Org. Biomol. Chem. 2018; 16: 7702
• 9e Wang Y, Wang B, Shao J, Xu D. CN 201810542160, 2018
• 10 Chloropyrazolones 3a–t; General Procedure A test tube was charged with Cu(ClO₄)₂ ·6H₂O (3.7 mg, 0.01 mmol), bisoxazoline Ia (4.6 mg, 0.01 mmol), and CH₂Cl₂ (1.0 mL), and the solution was stirred at r.t. for 0.5 h then cooled to –40 °C for 20 min. The appropriate pyrazolone 1 (0.1 mmol) and DCDMH (1.1 equiv, 0.11 mmol) were added and the mixture was stirred for 0.5 h until the reaction was complete (TLC). The mixture was then warmed to r.t. and purified directly by column chromatography (silica gel). The enantiomeric excess was determined by HPLC on a Chiralpak OD-H, AD-H, or OJ-H column. (4R)-4-Benzyl-4-chloro-2,5-diphenyl-2,4-dihydro-3H-pyrazol-3-one (3a) Yellow oil; yield: 35.3 mg (98%, 98% ee). [α]_D ²⁰ +64 (c 1.00, CH₂Cl₂). HPLC [Daicel Chiralpak AD-H, hexane–i-PrOH (90:10), 1.0 mL/min; λ = 336 nm]: t _R (major) = 10.026 min, t _R (minor) = 7.373 min. ¹H NMR (500 MHz, CDCl₃): δ = 8.14–8.05 (m, 2 H), 7.77–7.71 (m, 2 H), 7.60–7.50 (m, 3 H), 7.43–7.35 (m, 2 H), 7.26–7.19 (m, 1 H), 7.17–7.10 (m, 1 H), 7.11–7.04 (m, 2 H), 6.91–6.84 (m, 2 H), 3.78 (d, J = 13.2 Hz, 1 H), 3.71 (d, J = 13.2 Hz, 1 H). ¹³C NMR (126 MHz, CDCl₃) δ = 169.56, 155.09, 137.10, 131.91, 131.04, 129.76, 129.64, 128.99, 128.86, 128.43, 128.01, 126.82, 125.96, 119.54, 64.42, 44.04. HRMS (ESI+): m/z [M + H]⁺ calcd for C₂₂H₁₈ClN₂O: 361.1102; found: 361.1098.