Enantioselective Synthesis of 4-Silyl-1,2,3,4-tetrahydroquinolines via Copper(I) Hydride Catalyzed Asymmetric Hydrosilylation of 1,2-Dihydroquinolines

Dedicated to Prof. Barry M. Trost

Abstract

C–Si bonds were constructed by utilizing copper hydride-catalyzed asymmetric hydrosilylation of 1,2-dihydroquinolines, affording various chiral 4-silyl-1,2,3,4-tetrahydroquinolines in good yields and enantioselectivity. In addition, the C–Si bonds were transformed into C–O bonds with retention of stereochemistry through the Tamao oxidation, giving a series of useful 4-hydroxy-1,2,3,4-tetrahydroquinolines. This method with the enantioselective introduction of silyl groups provides an option to adjust bioactive properties of tetrahydroquinolines.

Key words

1,2-dihydroquinoline - 1,2,3,4-tetrahydroquinoline - copper hydride - asymmetric catalysis - hydrosilylation - dearomatization

• References and Notes

• 1a Meanwell NA. J. Med. Chem. 2011; 54: 2529
• 1b Lazareva NF, Lazarev IM. Russ. Chem. Bull. 2015; 64: 1221
• 1c Fujii S, Hashimoto Y. Future Med. Chem. 2017; 9: 485
• 1d Ramesh R, Reddy DS. J. Med. Chem. 2018; 61: 3779
• 2a Mills JS, Showell GA. Expert Opin. Invest. Drugs 2004; 13: 1149
• 2b Showell GA, Mills JS. Drug Discovery Today 2003; 8: 551
• 2c Franz AK, Wilson SO. J. Med. Chem. 2013; 56: 388
• 3 Fujii S. MedChemComm 2016; 7: 1082
• 4a Sieburth SMcN, Chen C.-A. Eur. J. Org. Chem. 2006; 311
• 4b Singh S, Sieburth SMcN. Org. Lett. 2012; 14: 4422
• 5 Svennebring A. J. Appl. Toxicol. 2016; 36: 483

For a review, see:
• 6a Gately S, West R. Drug Dev. Res. 2007; 68: 156

For selected examples:
• 6b Van Hattum AH, Pinedo HM, Schlüper HM. M, Hausheer FH, Boven E. Int. J. Cancer 2000; 88: 260
• 6c Seetharamsingh B, Ramesh R, Dange SS, Khairnar PV, Singhal S, Upadhyay D, Veeraraghavan S, Viswanadha S, Vakkalanka S, Reddy DS. ACS Med. Chem. Lett. 2015; 6: 1105
• 6d Jachak GR, Ramesh R, Sant DG, Jorwekar SU, Jadhav MR, Tupe SG, Deshpande MV, Reddy DS. ACS Med. Chem. Lett. 2015; 6: 1111
• 6e Kajita D, Nakamura M, Matsumoto Y, Ishikawa M, Hashimoto Y, Fujii S. Bioorg. Med. Chem. Lett. 2015; 25: 3350
• 6f Luger P, Dittrich B, Tacke R. Org. Biomol. Chem. 2015; 13: 9093
• 6g Toyama H, Sato S, Shirakawa H, Komai M, Hashimoto Y, Fujii S. Bioorg. Med. Chem. Lett. 2016; 26: 1817
• 6h Ramesh R, Shingare RD, Kumar V, Anand A, ;B. S.; Veeraraghavan S, Viswanadha S, Ummanni R, Gokhale R, Reddy DS. Eur. J. Med. Chem. 2016; 122: 723
• 6i Panayides J.-L, Mathieu V, Banuls LM. Y, Apostolellis H, Dahan-Farkas N, Davids H, Harmse L, Rey ME. C, Green IR, Pelly SC, Kiss R, Kornienko A, van Otterlo WA. L. Bioorg. Med. Chem. 2016; 24: 2716
• 7a Saito K, Kanai M. Heterocycles 2012; 86: 1565
• 7b Toutov AA, Liu W.-B, Betz KN, Stoltz BM, Grubbs RH. Nat. Protoc. 2015; 10: 1897
• 7c Toutov AA, Liu W.-B, Betz KN, Fedorov A, Stoltz BM, Grubbs RH. Nature 2015; 518: 80
• 8a Vivet B, Cavelier F, Martinez J. Eur. J. Org. Chem. 2000; 807
• 8b Cavelier F, Vivet B, Martinez J, Aubry A, Didierjean C, Vicherat A, Marraud M. J. Am. Chem. Soc. 2002; 124: 2917
• 8c Cavelier F, Marchand D, Martinez J, Sagan S. J. Pept. Res. 2004; 63: 290
• 8d Pujals S, Fernández-Carneado J, Kogan MJ, Martinez J, Cavelier F, Giralt E. J. Am. Chem. Soc. 2006; 128: 8479
• 8e Hernández D, Nielsen L, Lindsay KB, López-García MA, Bjerglund K, Skrydstrup T. Org. Lett. 2010; 12: 3528
• 8f Wang J, Ma C, Wu Y, Lamb RA, Pinto LH, DeGrado WF. J. Am. Chem. Soc. 2011; 133: 13844
• 8g Kim JK, Sieburth SMcN. J. Org. Chem. 2012; 77: 2901
• 9a Mortensen M, Husmann R, Veri E, Bolm C. Chem. Soc. Rev. 2009; 38: 1002
• 9b Rémond E, Martin C, Martinez J, Cavelier F. Chem. Rev. 2016; 116: 11654
• 10a Katritzky AR, Rachwal S, Rachwal B. Tetrahedron 1996; 52: 15031
• 10b Sridharan V, Suryavanshi PA, Menéndez JC. Chem. Rev. 2011; 111: 7157
• 10c Muñoz GD, Dudley GB. Org. Prep. Proced. Int. 2015; 47: 179
• 10d Muthukrishnan I, Sridharan V, Menéndez JC. Chem. Rev. 2019; 119: 5057

For selected reviews, see:
• 11a Masson G, Lalli C, Benohoud M, Dagousset G. Chem. Soc. Rev. 2013; 42: 902
• 11b Jiang X, Wang R. Chem. Rev. 2013; 113: 5515
• 11c Fochi M, Caruana L, Bernardi L. Synthesis 2014; 46: 135
• 11d Xie M, Lin L, Feng X. Chem. Rec. 2017; 17: 1184

For selected recent examples, see:
• 11e Gelis C, Levitre G, Guérineau V, Touboul D, Neuville L, Masson G. Eur. J. Org. Chem. 2019; 5151
• 11f Kazancioglu MZ, Kalay E, Kazancioglu EA, Peshkov VA. ChemistrySelect 2019; 4: 8797
• 11g Huang J.-X, Hou K.-Q, Hu Q.-L, Chen X.-P, Li J, Chan AS. C, Xiong X.-F. Org. Lett. 2020; 22: 1858
• 11h Li J, Gu Z, Zhao X, Qiao B, Jiang Z. Chem. Commun. 2019; 55: 12916
• 11i Jarrige L, Gandon V, Masson G. Chem. Eur. J. 2020; 26: 1406

For selected recent examples, see:
• 12a Mei G.-J, Li D, Zhou G.-X, Shi Q, Cao Z, Shi F. Chem. Commun. 2017; 53: 10030
• 12b Tukhvatshin RS, Kucherenko AS, Nelyubina YV, Zlotin SG. Eur. J. Org. Chem. 2018; 7000
• 12c Song Y.-X, Du D.-M. Org. Biomol. Chem. 2018; 16: 9390
• 12d Chen J, Han X, Lu X. Org. Lett. 2019; 21: 8153
• 13a Chen L, Zhang L, Lv J, Cheng J.-P, Luo S. Chem. Eur. J. 2012; 18: 8891
• 13b Suh CW, Woo SB, Kim DY. Asian J. Org. Chem. 2014; 3: 399
• 13c Cao W, Liu X, Guo J, Lin L, Feng X. Chem. Eur. J. 2015; 21: 1632

For other selected recent cyclization reactions, see:
• 14a Xu C, Feng Y, Li F, Han J, He Y.-M, Fan Q.-H. Organometallics 2019; 38: 3979
• 14b Xiong W, Li S, Fu B, Wang J, Wang Q.-A, Yang W. Org. Lett. 2019; 21: 4173
• 15a Levit GL, Gruzdev DA, Krasnov VP, Chulakov EN, Sadretdinova LSh, Ezhikova MA, Kodess MI, Charushin VN. Tetrahedron: Asymmetry 2011; 22: 185
• 15b Gruzdev DA, Chulakov EN, Levit GL, Ezhikova MA, Kodess MI, Krasnov VP. Tetrahedron: Asymmetry 2013; 24: 1240
• 15c Qin L, Zheng D, Cui B, Wan N, Zhou X, Chen Y. Tetrahedron Lett. 2016; 57: 2403

For selected reviews, see:
• 16a Wang D.-S, Chen Q.-A, Lu S.-M, Zhou Y.-G. Chem. Rev. 2012; 112: 2557
• 16b Zheng C, You S.-L. Chem. Soc. Rev. 2012; 41: 2498
• 16c Luo Y.-E, He Y.-M, Fan Q.-H. Chem. Rec. 2016; 16: 2697
• 16d Meng W, Feng X, Du H. Acc. Chem. Res. 2018; 51: 191
• 16e Meng W, Feng X, Du H. Chin. J. Chem. 2020; 38: 625

For selected recent examples, see:
• 16f Li B, Xu C, He Y.-M, Deng G.-J, Fan Q.-H. Chin. J. Chem. 2018; 36: 1169
• 16g Chen Y, He Y.-M, Zhang S, Miao T, Fan Q.-H. Angew. Chem. Int. Ed. 2019; 58: 3809
• 16h Hu X.-H, Hu X.-P. Org. Lett. 2019; 21: 10003
• 16i Liu Y, Chen F, He Y.-M, Li C, Fan Q.-H. Org. Biomol. Chem. 2019; 17: 5099
• 16j Chen Y, Pan Y, He Y.-M, Fan Q.-H. Angew. Chem. Int. Ed. 2019; 58: 16831
• 16k Li X, Tian J.-J, Liu N, Tu X.-S, Zeng N.-N, Wang X.-C. Angew. Chem. Int. Ed. 2019; 58: 4664
• 16l Tao L, Li C, Ren Y, Li H, Chen J, Yang Q. Chin. J. Catal. 2019; 40: 1548
• 16m Tao L, Ren Y, Li C, Li H, Chen X, Liu L, Yang Q. ACS Catal. 2020; 10: 1783
• 16n Wang L.-R, Chang D, Feng Y, He Y.-M, Deng G.-J, Fan Q.-H. Org. Lett. 2020; 22: 2251

For selected recent examples, see:
• 17a Fischer T, Duong Q.-N, Mancheño OG. Chem. Eur. J. 2017; 23: 5983
• 17b Duong Q.-N, Schifferer L, Mancheño OG. Eur. J. Org. Chem. 2019; 5452
• 18a Li G, Liu H, Wang Y, Zhang S, Lai S, Tang L, Zhao J, Tang Z. Chem. Commun. 2016; 52: 2304
• 18b Kubota K, Watanabe Y, Ito H. Adv. Synth. Catal. 2016; 358: 2379
• 18c Kong D, Han S, Wang R, Li M, Zi G, Hou G. Chem. Sci. 2017; 8: 4558
• 18d Kong D, Han S, Zi G, Hou G, Zhang J. J. Org. Chem. 2018; 83: 1924
• 18e Xu-Xu Q.-F, Zhang X, You S.-L. Org. Lett. 2019; 21: 5357
• 18f Xu-Xu Q.-F, Zhang X, You S.-L. Org. Lett. 2020; 22: 1530
• 18g For a related example, see: Kubota K, Watanabe Y, Hayama K, Ito H. J. Am. Chem. Soc. 2016; 138: 4338
• 19a Lukevics E, Germane S, Segal I, Zablotskaya A. Chem. Heterocycl. Compd. 1997; 33: 234
• 19b Gandhamsetty N, Joung S, Park S.-W, Park S, Chang S. J. Am. Chem. Soc. 2014; 136: 16780

For selected reviews, see:
• 20a Park S. Chin. J. Chem. 2019; 37: 1057
• 20b Wilkinson JR, Nuyen CE, Carpenter TS, Harruff SR, Hoveln RV. ACS Catal. 2019; 9: 8961

For selected recent examples, see:
• 20c Kan SB. J, Lewis RD, Chen K, Arnold FH. Science 2016; 354: 1048
• 20d Wang A, Bernasconi M, Pfaltz A. Adv. Synth. Catal. 2017; 359: 2523
• 20e Zuo Z, Xu S, Zhang L, Gan L, Fang H, Liu G, Huang Z. Organometallics 2019; 38: 3906
• 20f Chowdhury R, Dubey AK, Ghosh SK. J. Org. Chem. 2019; 84: 2404

For selected reviews, see:
• 21a Han JW, Hayashi T. Tetrahedron: Asymmetry 2014; 25: 479
• 21b Chen J, Guo J, Lu Z. Chin. J. Chem. 2018; 36: 1075
• 21c Chen J, Lu Z. Org. Chem. Front. 2018; 5: 260
• 21d Zaranek M, Pawluc P. ACS Catal. 2018; 8: 9865

For selected examples, see:
• 21e Yamamoto K, Hayashi T, Kumada M. J. Am. Chem. Soc. 1971; 93: 5301
• 21f Kiso Y, Yamamoto K, Tamao K, Kumada M. J. Am. Chem. Soc. 1972; 94: 4373
• 21g Uozumi Y, Hayashi T. J. Am. Chem. Soc. 1991; 113: 9887
• 21h Tamao K, Nakamura K, Ishii H, Yamaguchi S, Shiro M. J. Am. Chem. Soc. 1996; 118: 12469
• 21i Jensen JF, Svendsen BY, la Cour TV, Pedersen HL, Johannsen M. J. Am. Chem. Soc. 2002; 124: 4558
• 21j Naito T, Yoneda T, Ito J.-i, Nishiyama H. Synlett 2012; 23: 2957
• 21k Chen J, Cheng B, Cao M, Lu Z. Angew. Chem. Int. Ed. 2015; 54: 4661
• 21l Cheng B, Lu P, Zhang H, Cheng X, Lu Z. J. Am. Chem. Soc. 2017; 139: 9439
• 21m Zhao Z.-Y, Nie Y.-X, Tang R.-H, Yin G.-W, Cao J, Xu Z, Cui Y.-M, Zheng Z.-J, Xu L.-W. ACS Catal. 2019; 9: 9110
• 22a Trost BM, Dong G. J. Am. Chem. Soc. 2010; 132: 16403
• 22b Trost BM, Frontier AJ, Thiel OR, Yang H, Dong G. Chem. Eur. J. 2011; 17: 9762
• 22c Trost BM, Yang H, Brindle CS, Dong G. Chem. Eur. J. 2011; 17: 9777

For selected asymmetric examples, see:
• 23a Gribble M, W., Jr.; Pirnot MT, Bandar JS, Liu RY, Buchwald SL. J. Am. Chem. Soc. 2017; 139: 2192
• 23b Zhang L, Oestreich M. Chem. Eur. J. 2019; 25: 14304
• 23c Mao W, Xue W, Irran E, Oestreich M. Angew. Chem. Int. Ed. 2019; 58: 10723

For selected racemic versions, see:
• 23d Zhao X, Xu S, He J, Zhou Y, Cao S. Org. Chem. Front. 2019; 6: 2539
• 23e Wang H, Zhang G, Zhang Q, Wang Y, Li Y, Xiong T, Zhang Q. Chem. Commun. 2020; 56: 1819
• 24 Lipshutz BH, Noson K, Chrisman W, Lower A. J. Am. Chem. Soc. 2003; 125: 8779
• 25 Methyl (R)-4-(Diphenylsilyl)-3,4-dihydroquinoline-1(2H)-carboxylate (2a): Yield: 64.1 mg (86%); colorless oil; 87% ee [Daicel Chiralpak OD-H (0.46 cm × 25 cm), n-hexane/2-propanol = 90/10, v = 0.7 mL·min^–1, λ = 230 nm, t _R (major) = 12.59 min, t _R (minor) = 10.58 min]; [α]_D ²⁸ = +18.9 (c = 1.0, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.65–7.50 (m, 1 H), 7.50–7.44 (m, 2 H), 7.44–7.35 (m, 4 H), 7.35–7.26 (m, 4 H), 7.12–7.05 (m, 1 H), 6.92–6.85 (m, 2 H), 4.92 (d, J = 2.8 Hz, 1 H), 3.93 (dt, J = 12.4, 6.4 Hz, 1 H), 3.65 (s, 3 H), 3.31 (dt, J = 12.0, 6.0 Hz, 1 H), 2.99 (td, J = 6.8, 3.2 Hz, 1 H), 2.24–2.06 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 155.1, 138.1, 135.7, 135.6, 132.6, 132.5, 131.7, 130.0, 129.9, 128.5, 128.2, 128.1, 125.2, 124.7, 123.8, 52.8, 44.2, 26.2, 25.7. IR (thin film): 3057, 3010, 2945, 2123, 1699, 1587, 1487, 1435, 1377, 1329, 1249, 1193, 1113, 1048, 803, 736, 698, 582, 481, 434 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₃H₂₃NNaO₂Si: 396.1390; found: 396.1390.
• 26 General Procedure A: An oven-dried 10 mL screw-cap reaction tube with magnetic stir bar was charged with copper acetate (1.8 mg, 0.010 mmol, 5.0 mol%), (R,R)-Ph-BPE (5.6 mg, 0.011 mmol, 5.5 mol%) and tri(p-tolyl)phosphine (6.7 mg, 0.022 mmol, 11 mol%). It was evacuated and backfilled with argon three times. Diphenylsilane (111 μL, 0.6 mmol) was added by using a syringe and the resulting mixture was premixed for 30 min at 30 °C on a heating block. To the resulting orange mixture, 1,2-dihydroquinoline 1 (0.2 mmol) was added under argon atmosphere. The mixture was stirred for 36 h at 40 °C on a heating block. The mixture was diluted with ethyl acetate (20 mL), then the organic phase was allowed to pass through a short pad of silica gel with extra ethyl acetate (20 mL) as eluent. The filtrate was concentrated in vacuo and the crude mixture was purified by silica gel column chromatography (PE/EtOAc = 100:1 to 40:1, v/v) or preparative TLC (PE/EtOAc = 40:1, v/v) affording product 2.
• 27 General Procedure B: An oven-dried 10 mL screw-cap reaction tube with magnetic stir bar was charged with copper acetate (1.8 mg, 0.010 mmol, 5.0 mol%), (R,R)-Ph-BPE (5.6 mg, 0.011 mmol, 5.5 mol%) and tri(p-tolyl)phosphine (6.7 mg, 0.022 mmol, 11 mol%). It was evacuated and backfilled with argon for three times. Phenylsilane (74 μL, 0.6 mmol) was added by using a syringe and the resulting mixture was premixed at r.t. for 5 min. To the resulting orange mixture, 1,2-dihydroquinoline 1 (0.2 mmol) was added under argon atmosphere. The mixture was stirred for 36 h at 40 °C on a heating block. The volatiles were removed in vacuo with an oil pump at room temperature and the crude product was used for the next step without further purification. To a 25 mL Schlenk tube were added potassium fluoride (46.5 mg, 0.8 mmol), K₂EDTA·(H₂O)₂ (80.9 mg, 0.2 mmol) and potassium bicarbonate (80.1 mg, 0.8 mmol) and the tube was evacuated and backfilled with argon for three times. The crude product was dissolved in THF (1 mL) and transferred to the Schlenk tube by using a syringe. The residue was further rinsed with THF (0.1 mL × 2) and added to the tube. To the resulting mixture was added methanol (1.2 mL) dropwise and gas was released. The mixture was stirred at room temperature for 40 min, then hydrogen peroxide (0.23 g, 27% w/w in water, 1.8 mmol) was added and the suspension was stirred at room temperature for 20 h. The reaction was quenched with sodium thiosulfate (0.85 g, 5.4 mmol) with extra methanol (2 mL). After peroxide residue was quenched completely as indicated by starch-iodine indicator paper, the mixture was diluted by ethyl acetate (5 mL), dried over magnesium sulfate, filtered by glass-sintered filter, rinsed with extra ethyl acetate (20 mL) and concentrated in vacuo. The crude product was purified by silica gel column chromatography (PE/EtOAc = 10:1 to 2:1, v/v) or preparative TLC (PE/EtOAc = 2:1, v/v) afford product 3.
• 28 Methyl (R)-4-Hydroxy-3,4-dihydroquinoline-1(2H)-carboxylate (3a): Yield: 26.0 mg (63%); colorless oil; 89% ee [Daicel Chiralpak IG (0.46 cm × 25 cm), n-hexane/2-propanol = 95:5, v = 1.0 mL·min^–1, λ = 230 nm, t _R (major) = 36.31 min, t _R (minor) = 33.64 min]; [α]_D ²¹ = +25.6 (c = 1.0, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.80 (d, J = 8.4 Hz, 1 H), 7.38 (d, J = 7.6 Hz, 1 H), 7.26 (t, J = 8.0 Hz, 1 H), 7.09 (t, J = 7.6 Hz, 1 H), 4.80–4.70 (m, 1 H), 4.07 (dt, J = 13.2, 5.2 Hz, 1 H), 3.79 (s, 3 H), 3.64 (ddd, J = 13.6, 10.0, 4.4 Hz, 1 H), 2.18 (s, 1 H), 2.14–1.93 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 155.1, 137.4, 130.8, 128.4, 128.3, 124.0, 123.4, 65.8, 53.1, 40.7, 31.9. IR (thin film): 3399, 2953, 1681, 1605, 1581, 1490, 1439, 1377, 1331, 1245, 1217, 1192, 1134, 1083, 1054, 1037, 1021, 976, 943, 911, 865, 821, 756, 702, 591, 560, 530, 491 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₁H₁₃NNaO₃: 230.0788; found: 230.0791.
• 29 CCDC 1996641 contains the supplementary crystallographic data for compound 4. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 30a Fu P.-F, Brard L, Li Y, Marks TJ. J. Am. Chem. Soc. 1995; 117: 7157
• 30b Chen Y, Sui-Seng C, Boucher S, Zargarian D. Organometallics 2005; 24: 149
• 30c Noh D, Chea H, Ju J, Yun J. Angew. Chem. Int. Ed. 2009; 48: 6062
• 30d Noh D, Yoon SK, Won J, Lee JY, Yun J. Chem. Asian J. 2011; 6: 1967
• 30e Xi Y, Hartwig JF. J. Am. Chem. Soc. 2017; 139: 12758