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DOI: https://doi.org/10.6023/A25120419

Article

One-pot, Catalytic Asymmetric Reductive Bischler-Napieralski-Type Reaction of Amides: An Enantioselective Entrance to Biologically Active 1-Substituted Tetrahydroisoquinolines

  • Lu Guang-Sheng ,
  • Han Zeng ,
  • Ye Jian-Liang ,
  • Huang Pei-Qiang
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  • Fujian Key Laboratory of Chemical Biology (Xiamen University), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China

Received date: 2025-12-25

  Online published: 2026-01-09

Supported by

National Natural Science Foundation of China (22571267 and 21931010).

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Abstract

Herein, we report the one-pot, catalytic asymmetric reductive Bischler-Napieralski-type reaction of amides as the first demonstration of a new strategy for the asymmetric reductive transformation of amides, which allowed for the one-pot, enantioselective entrance to tetrahydroisoquinoline (THIQ). The method features a tandem sequence involving the Tf2O/2-F-Pyr.-promoted Bischler-Napieralski dehydracyclization and an aqueous Noyori-type catalytic asymmetric transfer hydrogenation (CATH). By this one-pot method, a variety of THIQ derivatives were synthesized in high yields and in excellent enantioselectivities. This protocol accommodates N-arylethyl aromatic amides bearing either electron-rich or electron-deficient group on the acyl moiety, and N-arylethyl aliphatic amides. The synthetic utility of this methodology was demonstrated via the efficient, catalytic enantioselective synthesis of four alkaloids: (S)-salsolidine, (S)-laudanosine, (S)-xylopinine, and (S)-N-norlaudanidine, and medicinal agent ACT-335827. Additionally, formal synthesis of alkaloid (S)-cryptostyline III and medicinal agents such as almorexant was achieved.

Key words： amide; amide activation; tetrahydroisoquinoline; Bischler-Napieralski-type cyclization; catalytic asymmetric transfer hydrogenation; alkaloid

Cite this article

Lu Guang-Sheng , Han Zeng , Ye Jian-Liang , Huang Pei-Qiang . One-pot, Catalytic Asymmetric Reductive Bischler-Napieralski-Type Reaction of Amides: An Enantioselective Entrance to Biologically Active 1-Substituted Tetrahydroisoquinolines[J]. Acta Chimica Sinica, 0 : 20260109 . DOI: 10.6023/A25120419

References

[1] (a) Wender, P. A.; Verma, V. A.; Paxton, T. J.; Pillow, T. H. Acc. Chem. Res. 2008, 41, 40. (b) Li, C.-J.; Trost, B. M. Proc. Nat. Acad. Sci., 2008, 105, 13197. (c) Newhouse, T.; Baran, P. S.; Hoffmann, R. W. Chem. Soc. Rev. 2009, 38, 3010. (d) Hayashi, Y. Chem. Sci. 2016, 7, 866. (e) Huang, P.-Q. In Efficiency in Natural Product Total Synthesis, Eds: Huang, P.-Q.; Yao, Z.-J. & Hsung, R. P., John Wiley & Sons, Inc., 2018, Chapters 1-2. (f) Gao, Y.; Ma, D. W. Acc. Chem. Res. 2021, 54, 569. (g) Hayashi, Y. Acc. Chem. Res. 2021, 54, 1385. (h) Kar, S.; Sanderson, H.; Roy, K.; Benfenati, E.; Leszczynski, J. Chem. Rev. 2022, 122, 3637. (i) Zhao, Y.-C.; Yu, B. Acta Chim. Sinica 2025, 83, 1397 (in Chinese). (赵雅宸, 俞飚, 化学学报 2025, 83, 1397). (j) Chen, R.; Liu, Y.; Ding, H. Org. Chem. Front., 2025, 12, 2415. (k) Jiang, P.-Y.; Wu, S.; Wang, J.; Xiang, S.-H.; Tan, B. Org. Chem. Front., 2025, 12, 4126. for selected recent examples, see: (l) Gan, K.-J.; Zhu, Y.; Shi, G.; Wu, C.; Ni, F.-Q.; Zhao, L.-H.; Dou, X.; Zhang, Z.; Lu, H.-H. Chin. J. Chem. 2025, 43, 79. (m) Zuo, H.; Hu, Y.; Qiao, X.; Zhang, Y.; Wang S. Acta Chim. Sinica 2025, 83, 981 (in Chinese). (左恒昕宇, 虎亚光, 乔霞, 张野, 王少华, 化学学报, 2025, 83, 981.)
[2] (a) Falmagne, J.-B.; Escudero, J.; Taleb-Sahraoui, S.; Ghosez, L.Angew. Chem. Int. Ed. 1981, 20, 879. (b) Ghosez, L. Tetrahedron 2019, 75, 130345.
[3] For selected examples, see:(a) Bechara, W. S.; Pelletier, G.; Charette, A. B.Nat. Chem. 2012, 4, 228. (b) Barbe, G.; Charette, A. B. J. Am. Chem. Soc. 2008, 130, 1. (c) Pelletier, G.; Bechara, W. S.; Charette, A. B. J. Am. Chem. Soc. 2010, 132, 12817. (d) Charette, A. B.; Grenon, M. Can. J. Chem. 2001, 79, 1694.
[4] For selected examples see: (a) White K. L.; Mewald M.; Movassaghi, M. J. Org. Chem. 2015, 80,7403. (b) Movassaghi, M.; Hill, M. D.Org. Lett. 2008, 10, 3485. (c) Movassaghi, M.; Hill, M. D.; Ahmad, O. K. J. Am. Chem. Soc. 2007, 129, 10096. (d) Movassaghi, M.; Hill, M. D. J. Am. Chem. Soc. 2006, 128, 14254. (e) Medley, J. W.; Movassaghi, M. J. Org. Chem. 2009, 74, 1341.
[5] For reviews see: (a) Pace V.; Holzer, W. Aust. J. Chem. 2013, 66, 507. (b) Pace V.; Holzer W.; Olofsson, B. Adv. Synth. Catal. 2014, 356,3697. (c) Volkov, A.; Tinnis, F.; Slagbrand, T.; Trillo, P.; Adolfsson, H.Chem. Soc. Rev. 2016, 45, 6685. (d) Kaiser, D.; Bauer, A.; Lemmerer, M.; Maulide, N. Chem. Soc. Rev. 2018, 47, 7899. (e) Sato, T.; Yoritate, M.; Tajima, H.; Chida, N. Org. Biomol. Chem. 2018, 16, 3864. (f) Matheau-Raven, D.; Gabriel, P.; Leitch, J. A.; Almehmadi, Y. A.; Yamazaki, K.; Dixon, D. J. ACS Catal. 2020, 10, 8880. (g) Tahara, A.; Nagashima, H. Tetrahedron Lett. 2020, 61, 151423. (h) Czerwiński, P. J.; Furman, B. Trends Chem. 2020, 2, 782. (i) Czerwinski, P. J.; Furman, B. Front. Chem. 2021, 9, 655849. (j) Huang, H.; Kang, J. Y. Synthesis 2022, 54, 1157. (k) Luo, Y. Sci. Sin. Chim. 2023, 53, 129, corrigendum: Luo, Y. Sci. Sin. Chim. 2024, 54, 968. (l) Ou, W.; Huang, P.-Q. Acc. Chem. Res. 2025, 58, 2332.
[6] For selected examples, see:(a) Yasui, S.; Aoki, S.; Okamura, T.; Sato, T.Chem. Lett. 2025, 54, upaf094. (b) Iwamoto, S.; Nakano, R.; Sasaki, K.; Kobayashi, S.; Taira, Y.; Takei, K.; Kawakita, R.; Tokuyama, A.; Nakamura, H.; Tomoike, M.; Kawahara, R.; Murase, A.; Simizu, S.; Chida, N.; Okamura, T.; Sato, T. Angew. Chem., Int. Ed. 2025, 64, e202508062. (c) Sugiyama, Y.; Yamada, K.; Kaneko, D.; Kusagawa, Y.; Okamura, T.; Sato, T. Angew. Chem. Int. Ed. 2024, 63, e202317290. (d) Iwamoto, S.; Tokuyama, A.; Hiraoka, S.; Takei, K.; Matsuzaka, K.; Matsumoto, T.; Chida, N.; Sato, T. Bull. Chem. Soc. Jpn. 2023, 96, 529. (e) Iiyama, S.; Mizutani, K.; Sato, T. Chem. Lett. 2023, 52, 682. (f) Yoritate, M.; Takahashi, Y.; Tajima, H.; Ogihara, C.; Yokoyama, T.; Soda, Y.; Oishi, T.; Sato, T.; Chida, N. J. Am. Chem. Soc. 2017, 139, 18386. (g) Shirokane, K.; Kurosaki, Y.; Sato, T.; Chida, N. Angew. Chem., Int. Ed. 2010, 49, 6369.
[7] For selected examples see: (a) Pijper B.; Martin R.; Huertas-Alonso A. J.; Linares M. L.; Lopez E.; Llaveria J.; Diaz-Ortiz A.; Dixon D. J.; de la Hoz A.; Alcazar, J. Org. Lett. 2024, 26,2724. (b) Miller, A. A. M.; Biallas, P.; Shennan, B. D. A.; Dixon, D. J.Angew. Chem. Int. Ed. 2024, 63, e202314308. (c) Matheau-Raven, D.; Dixon, D. J. Angew. Chem., Int. Ed. 2021, 60, 19725. (d) Fuentes de Arriba, A. L.; Lenci, E.; Sonawane, M.; Formery, O.; Dixon, D. J. Angew. Chem., Int. Ed. 2017, 56, 3655. (e) Gregory, A. W.; Chambers, A.; Hawkins, A.; Jakubec, P.; Dixon, D. J. Chem.-Eur. J. 2015, 21, 111.
[8] For catalytic asymmetric reductive transformations, see: (a) Ji, K.-L.; He, S.-F.; Xu, D.-D.; He, W.-X.; Zheng, J.-F.; Huang, P.-Q. Angew. Chem. Int. Ed. 2023, 62, e202302832. (b) Xu, F.-F.; Chen, J.-Q.; Shao, D.-Y.; Huang, P.-Q. Nat. Commun. 2023, 14, 6251. (c) Chen, H.; Wu, Z.-Z.; Shao, D.-Y.; Huang, P.-Q. Sci. Adv. 2022, 8, eade3431. (d) Chen, D.-H.; Sun, W.-T.; Zhu, C.-J.; Lu, G.-S.; Wu, D.-P.; Wang, A.-E; Huang, P.-Q. Angew. Chem. Int. Ed. 2021, 60, 8827. (e) Xu, Z.; Wang, X.-G.; Wei, Y.-H.; Ji, K.-L.; Zheng, J.-F.; Ye, J.-L.; Huang, P.-Q. Org. Lett. 2019, 21, 7587. For selected non-asymmetric transformations, see: (f) Weng, Z.-Y.; Li, Y.-Q.; He, W.-X.; Chen, Z.-Y.; Huang, P.-Q. CCS Chem. doi: 10.31635/ccschem.025.202506810. (g) Liu, M.-H.; Sun, W.-T.; Yang, A.-Q.; Wang, Z.; Chang, Z.; Wang, A.-E; Huang, P.-Q. Sci. China Chem. doi: 10.1007/s11426-025-2935-3. (h) Xu, Y.-P.; Ruan, Y.; Zheng, J.-F.; Huang, P.-Q. Chin. J. Org. Chem. 2025, 45, 988 (in Chinese) (徐业鹏, 阮义, 郑剑峰, 黄培强, 有机化学, 2025, 45, 988.) (i) Chen, L.-N.; Jin, Z.-K.; Ye, J.-L.; Huang, P.-Q. Arkivoc 2024, 202412191. (j) Han, F.; Lu, G.-S.; Wu, D.-P.; Huang, P.-Q. Sci. China Chem. 2023, 66, 1094. (k) He, Q.; Li, J.; Yu, S.-J.; Wu, D.-P.; Ye, J.-L.; Huang, P.-Q. Acta Chim. Sinica 2023, 81, 1265 (in Chinese). (何倩, 李杰, 喻思佳, 吴东坪, 叶剑良, 黄培强, 化学学报, 2023, 81, 1265.) (l) Huang, P.-Q.; Ou, W.; Han, F. Chem. Commun. 2016, 52, 11967. (m) Xiao, K.-J.; Luo, J.-M.; Ye, K.-Y.; Wang, Y.; Huang, P.-Q. Angew. Chem., Int. Ed. 2010, 49, 3037.
[9] For selected examples see: (a) Pace V.; de la Vega-Hernandez K.; Urban E.; Langer, T. Org. Lett. 2016, 18,2750. (b) Miele, M.; Castoldi, L.; Beccalli, E.; Pace, V.Adv. Synth. Catal. 2024, 366, 2277. (c) Senatore, R.; Ielo, L.; Monticelli, S.; Castoldi, L.; Pace, V. Synthesis 2019, 51, 2792. (d) Touqeer, S.; Senatore, R.; Malik, M.; Urban, E.; Pace, V. Adv. Synth. Catal. 2020, 362, 5056.
[10] For selected examples see: (a) Szczesniak P.; Stecko S.; Staszewska-Krajewska O.; Furman, B. Tetrahedron 2014, 70,1880. (b) Szczesniak, P.; Maziarz, E.; Stecko, S.; Furman, B.J. Org. Chem. 2015, 80, 3621.
[11] For selected examples see: (a) Li Z.; Zhao F.; Ou W.; Huang P.-Q.; Wang, X. Angew. Chem., Int. Ed. 2021, 60, 26604. (b) Jiao J.-W.; Wang, X.-M. Angew. Chem., Int. Ed.2021, 60, 17088. (c) Li, J.; He, Y.; Jiang, F.; Wang, X. Green Chem. 2023, 25, 9080.
[12] For selected examples see: (a) Fang W.; Luo Z.-W.; Wang Y.-C.; Zhou W.; Li L.; Chen Y.; Zhang X.; Dai M.; Dai, J.-J. Angew. Chem. Int. Ed. 2024, 63, e202317570. (b) Lu J. X.; Li Z. H.; Deng, L. J. Am. Chem. Soc.2024, 146, 4357. (c) Shi, Q.; Liu, W. H. Angew. Chem. Int. Ed. 2023, 62, e202309567. (d) Tang, Z.; Mo, K.; Ma, X.; Huang, J.; Zhao, D. Angew. Chem. Int. Ed. 2022, 61, e202208089. (e) Agrawal, T.; Perez-Morales, K. D.; Cort, J. A.; Sieber, J. D. J. Org. Chem. 2022, 87, 6387. (f) Trillo, P.; Slagbrand, T.; Adolfsson, H. Angew. Chem., Int. Ed. 2018, 57, 12347. (g) Cheng, C.; Brookhart, M. J. Am. Chem. Soc. 2012, 134, 11304. (h) Motoyama, Y.; Aoki, M.; Takaoka, N.; Aoto, R.; Nagashima, H. Chem. Commun. 2009, 1574. For a recent application, see:(i) Huang, W.-W.; Cheng, J.-T.; Hsiao, W.-T.; Chiou, W.-H. J. Org. Chem. 2024, 89, 5091. For the reaction of vinylogous amides, see:, 373.
[13] For selected examples, see:(a) Heindl, S.; Riomet, M.; Matyasovsky, J.; Lemmerer, M.; Malzer, N.; Maulide, N.Angew. Chem., Int. Ed. 2021, 60, 19123. (b) Spieß, P.; Berger, M.; Kaiser, D.; Maulide, N. J. Am. Chem. Soc. 2021, 143, 10524. (c) Li, J.; Berger, M.; Zawodny, W.; Simaan, M.; Maulide, N. Chem 2019, 5, 1883.
[14] (a) Kim A. N.; Ngamnithiporn A.; Du E.; Stoltz, B. M. Chem. Rev. 2023, 123,9447. (b) Chrzanowska, M.; Grajewska, A.; Rozwadowska, M. D.Chem. Rev. 2016, 116, 12369. (c) Capilla, A. S.; Soucek, R.; Grau, L.; Romero, M.; Rubio-Martínez, J.; Caignard, D. H.; Pujol, M. D. Eur. J. Med. Chem. 2018, 145, 51.
[15] (a) Noyori R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97. (b) Uematsu N.; Fujii A.; Hashiguchi S.; Ikariya T.; Noyori, R. J. Am. Chem. Soc. 1996, 118,4916. (c) Lee, K. M.; Kim, J. C.; Kang, P.; Lee, W. K.; Eum, H.; Ha, H.-J.Tetrahedron 2012, 68, 883. (d) Ružič, M.; Pečavar, A.; Prudič, D.; Kralj, D.; Scriban, C.; Zanotti-Gerosa, A. Org. Process Res. Dev. 2012, 16, 1293. (e) Chrzanowska, M.; Rozwadowska, M. D. Chem. Rev. 2004, 104, 3341. (f) Václavíková Vilhanová, B.; Budinská, A.; Václavík, J.; Matoušek, V.; Kuzma, M.; Červený, L. Eur. J. Org. Chem. 2017, 5131. (g) Balázsik, K.; Szőllősi, G.; Berkesi, O.; Szalontai, G.; Fülöp, F.; Bartók, M. Top. Catal. 2012, 55, 880. (h) Ding, Z.-Y.; Wang, T.; He, Y.-M.; Chen, F.; Zhou, H.-F.; Fan, Q.-H.; Guo, Q.; Chan, A. S. C. Adv. Synth. Catal. 2013, 355, 3727. (i) Ji, Y.; Gao, Q.; Han, W.; Fang, B. Catalysts 2024, 14, 884.
[16] (a) Szawkało J.; Zawadzka A.; Wojtasiewicz K.; Leniewski A.; Drabowicz J.; Czarnocki, Z. Tetrahedron: Asymmetry 2005, 16,3619. (b) Perez, M.; Wu, Z.; Scalone, M.; Ayad, T.; Ratovelomanana-Vidal, V.Eur. J. Org. Chem. 2015, 2015, 6503. (c) Peng, P.; Zheng, Z.; Yu, J.; Gao, X.; Yang, J.; Zhao, C.; Zhang, F. Org. Process Res. Dev. 2022, 26, 3106.
[17] He Q.; Ye J.-L.; Xu F.-F.; Geng H.; Chen T.-T.; Chen H.; Huang P.-Q.J. Org.Chem. 2021, 86, 16300, and references cited therein.
[18] (a) Ogo S.; Abura T.; Watanabe, Y. Organometallics 2002, 21,2964. (b) Rhyoo, H. Y.; Park, H.-J.; Suh, W. H.; Chung, Y. K.Tetrahedron Lett. 2002, 43, 269. (c) Wang, F.; Liu, H.; Cun, L.; Zhu, J.; Deng, J.; Jiang, Y. J. Org. Chem. 2005, 70, 9424. (d) Wu, X.; Li, X.; Hems, W.; King, F.; Xiao, J. Org. Biomol. Chem. 2004, 2, 1818. (e) Li, C.; Xiao, J. J. Am. Chem. Soc. 2008, 130, 13208. (f) Evanno, L.; Ormala, J.; Pihko, P. M. Chem. Eur. J. 2009, 15, 12963.
[19] Bembenek M. E.; Abell C. W.; Chrisey L. A.; Rozwadowska M. D.; Gessner W.; Brossi A.J. Med. Chem. 1990, 33, 147.
[20] Xu C.-P.; Xiao Z.-H.; Zhuo B.-Q.; Wang Y.-H.; Huang P.-Q.Chem. Commun. 2010, 46, 7834.
[21] Mujahidin D.; Doye S.Eur. J. Org. Chem. 2005, 2689.
[22] Chuliá S.; Ivorra M. D.; Lugnier C.; Vila E.; Noguera M. A.; D'Ocon, P.Br. J. Pharmacol. 1994, 113, 1377.
[23] Fodale V.; Santamaria L. B.Eur. J. Anaesthesiology 2002, 19, 466.
[24] (a) Li W.; Jiang M.; Chen W.; Chen Y.; Yang Z.; Tang P.; Chen, F. J. Org. Chem. 2021, 86,8143. (b) Mastranzo, V. M.; Yuste, F.; Ortiz, B.; Sánchez-Obregón, R.; Toscano, R. A.; García Ruano, J. L.J. Org. Chem. 2011, 76, 5036.
[25] Steiner M. A.; Gatfield J.; Brisbare-Roch, C.; Dietrich, H.; Treiber, A.; Jenck, F.; Boss, C.ChemMedChem 2013, 8, 898.
[26] (a) Ji, Y.; Wang, J.; Chen, M.; Shi, L.; Zhou, Y.Chin. J. Chem. 2018, 36, 139. (b) Gitto, R.; Ficarra, R.; Stancanelli, R.; Guardo, M.; De Luca, L.; Barreca, M. L.; Pagano, B.; Rotondo, A.; Bruno, G.; Russo, E.; De Sarro, G.; Chimirri, A. Bioorg. Med. Chem. 2007, 15, 5417.
[27] (a) Sakurai, T.; Amemiya, A.; Ishii, M.; Matsuzaki, I.; Chemelli, R. M.; Tanaka, H.; Williams, S. C.; Richardson, J. A.; Kozlowski, G. P.; Wilson, S.; Arch, J. R. S.; Buckingham, R. E.; Haynes, A. C.; Carr, S. A.; Annan, R. S.; McNulty, D. E.; Liu, W.-S.; Terrett, J. A.; Elshourbagy, N. A.; Bergsma, D. J.; Yanagisawa, M.Cell 1998, 92, 573. (b) Reddy, N. S. S.; Reddy, B. V. S. Tetrahedron Lett. 2014, 55, 3157.
[28] (a) Leander, K.; Luning, B.; Ruusa, E.Acta Chem. Scand. 1969, 23, 244. (b) Brossi, A.; Teitel, S. Helv. Chim. Acta 1971, 54, 1564.
[29] Minor D. L.; Wyrick S. D.; Charifson P. S.; Watts V. J.; Nichols D. E.; Mailman R. B.J. Med. Chem. 1994, 37, 4317.
[30] Capilla A. S.; Soucek R.; Grau L.; Romero M.; Rubio-Martínez, J.; Caignard, D. H.; Pujol, M. D.Eur. J. Med. Chem. 2018, 145, 51.
[31] Zein A. L.; Dakhil O. O.; Dawe L. N.; Georghiou P. E.Tetrahedron Lett. 2010, 51, 177.
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