Divergent Hydrogenation of Indoles and Its Applications in Total Syntheses of (±)-α- and γ-Lycoranes

doi:10.6023/cjoc202501010

Abstract

Hydroindoles are highly enriched in a variety of medicines, natural products, materials, and agrochemicals, however rapid and efficient access of this type of structure is still formidable. Herein, the construction of hydroindoles via hydrogenation of substituted indoles under atmospheric pressure of H₂ at relatively low temperatures utilizing Pd/C as the catalyst is reported. And the controlled divergent hydrogenation of substituted indoles to dihydroindoles, tetrahydroindoles, hexahydroindoles, or octahydroindoles could be achieved by careful manipulation of reaction parameters, including reaction solvents, catalyst loading, and temperature. The efficiency of this method was demonstrated by the divergent syntheses of (±)-α- and γ-lycoranes in a three-step synthetic route.

Key words: total synthesis, α-lycorane, γ-lycorane, hydroindole, hydrogenation

Cite this article

Shoule Han, Mingliang Lou, Xiaolei Liu, Gen Li, Xin Wang, Qingcui Wu, Xiangbing Qi. Divergent Hydrogenation of Indoles and Its Applications in Total Syntheses of (±)-α- and γ-Lycoranes[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 913-924.

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References 15

[1]	Luo, R. S.; Weng, J.; Ai, H. B.; Lu, G.; Chan, A. S. C. Adv. Synth. Catal. 2009, 351, 2449.
[2]	Hurst, M.; Jarvis, B. Drugs 2001, 61, 867.
[3]	(a) Faulkner, A.; Bower, J. F. Angew. Chem., Int. Ed. 2012, 51, 1675.
	(b) Sofack-Kreutzer, J.; Martin, N.; Renaudat, A.; Jazzar, R.; Baudoin, O. Angew. Chem., Int. Ed. 2012, 51, 10399.
	(c) Diethelm, S.; Schindler, C. S.; Carreira, E. M. Chem. Eur. J. 2014, 20, 6071.
	(d) Feng, M.; Jiang, X. Chem. Commun. 2014, 50, 9690.
	(e) Han, Y.; Zheng, B.; Peng, Y. Adv. Synth. Catal. 2015, 357, 1136.
	(f) Gan, P.; Smith, M. W.; Braffman, N. R.; Snyder, S. A. Angew. Chem., Int. Ed. 2016, 55, 3625.
	(g) MacLeod, B. L.; Pienkos, J. A.; Wilson, K. B.; Sabat, M.; Myers, W. H.; Harman, W. D. Organometallics 2016, 35, 370.
	(h) Kalaitzakis, D.; Triantafyllakis, M.; Ioannou, G. I.; Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2017, 56, 4020.
	(i) Yang, H.; Hou, S.; Tao, C.; Liu, Z.; Wang, C.; Cheng, B.; Li, Y.; Zhai, H. Chem. Eur. J. 2017, 23, 12930.
	(j) Zhao, Q.-S.; Xu, G.-Q.; Xu, J.-T.; Wang, Z.-Y.; Xu, P.-F. Chem. Commun. 2020, 56, 2206.
	(k) Wang, F.; Xu, X.-H.; Yan, Y.-T.; Zhang, J.-Y.; Bai, W.-J.; Chen, J.-W.; Yang, Y. Org. Lett. 2023, 25, 6853.
[4]	(a) Wang, D.-S.; Chen, Q.-A.; Lu, S.-M.; Zhou, Y.-G. Chem. Rev. 2011, 112, 2557.
	(b) Wiesenfeldt, M. P.; Nairoukh, Z.; Dalton, T.; Glorius, F. Angew. Chem., Int. Ed. 2019, 58, 10460.
	(c) Kim, A. N.; Stoltz, B. M. ACS Catal. 2020, 10, 13834.
	(d) Lückemeier, L.; Pierau, M.; Glorius, F. Chem. Soc. Rev. 2023, 52, 4996.
[5]	(a) Xu, L.; Zhang, C.; He, Y.; Tan, L.; Ma, D. Angew. Chem., Int. Ed. 2015, 55, 321.
	(b) Yang, Y.; Li, R.; Zhao, Y.; Zhao, D.; Shi, Z. J. Am. Chem. Soc. 2016, 138, 8734.
	(c) Yang, Y.; Qiu, X.; Zhao, Y.; Mu, Y.; Shi, Z. J. Am. Chem. Soc. 2016, 138, 495.
	(d) Yang, Y.; Gao, P.; Zhao, Y.; Shi, Z. Angew. Chem., Int. Ed. 2017, 57, 3966.
	(e) Qiu, X.; Wang, P.; Wang, D.; Wang, M.; Yuan, Y.; Shi, Z. Angew. Chem., Int. Ed. 2018, 58, 1504.
[6]	(a) Kuwano, R.; Sato, K.; Kurokawa, T.; Karube, D.; Ito, Y. J. Am. Chem. Soc. 2000, 122, 7614.
	(b) Kuwano, R. K.; Kaneda, K.; Ito, T.; Sato, K.; Kurokawa, T.; Ito, Y. Org. Lett. 2004, 6, 2213.
	(c) Kuwano, R.; Kashiwabara, M. Org. Lett. 2006, 8, 2653.
	(d) Baeza, A.; Pfaltz, A. Chem. Eur. J. 2010, 16, 2036.
	(e) Wang, D.-S.; Chen, Q.-A.; Li, W.; Yu, C.-B.; Zhou, Y.-G.; Zhang, X. J. Am. Chem. Soc. 2010, 132, 8909.
	(f) Li, C.; Chen, J.; Fu, G.; Liu, D.; Liu, Y.; Zhang, W. Tetrahedron 2013, 69, 6839.
	(g) Duan, Y.; Li, L.; Chen, M.-W.; Yu, C.-B.; Fan, H.-J.; Zhou, Y.-G. J. Am. Chem. Soc. 2014, 136, 7688.
	(h) Núñez-Rico, J. L.; Fernández-Pérez, H.; Vidal-Ferran, A. Green Chem. 2014, 16, 1153.
	(i) Yang, Z.; Chen, F.; He, Y.; Yang, N.; Fan, Q. H. Angew. Chem., Int. Ed. 2016, 55, 13863.
	(j) Touge, T.; Arai, T. J. Am. Chem. Soc. 2016, 138, 11299.
	(k) Wen, J.; Fan, X.; Tan, R.; Chien, H.-C.; Zhou, Q.; Chung, L. W.; Zhang, X. Org. Lett. 2018, 20, 2143.
	(l) Ge, Y.; Wang, Z.; Han, Z.; Ding, K. Chem. Eur. J. 2020, 26, 15482.
	(m) Liu, G.; Zheng, L.; Tian, K.; Wang, H.; Wa Chung, L.; Zhang, X.; Dong, X.-Q. CCS Chem. 2023, 5, 1398.
[7]	(a) Clarisse, D.; Fenet, B.; Fache, F. Org. Biomol. Chem. 2012, 10, 6587.
	(b) Wollenburg, M.; Moock, D.; Glorius, F. Angew. Chem., Int. Ed. 2018, 57, 6549.
	(c) Ling, L.; He, Y.; Zhang, X.; Luo, M.; Zeng, X. Angew. Chem., Int. Ed. 2019, 58, 6554.
	(d) Wagener, T.; Pierau, M.; Heusler, A.; Glorius, F. Adv. Synth. Catal. 2022, 364, 3366.
	(e) Zhang, F.; Sasmal, H. S.; Daniliuc, C. G.; Glorius, F. J. Am. Chem. Soc. 2023, 145, 15695.
[8]	(a) Aminzai, M. T.; Azizi, N.; Nural, Y.; Yabalak, E. Monatsh. Chem.-Chem. Mon. 2024, 155, 115.
	(b) Luo, C.; Wu, C.; Wang, X.; Han, Z.; Wang, Z.; Ding, K. J. Am. Chem. Soc. 2024, 146, 35043.
	(c) Williams, S.; Qi, L.; Cox, R. J.; Kumar, P.; Xiao, J. Org. Biomol. Chem. 2024, 22, 1010.
	(d) Luckemeier, L.; Pierau, M.; Glorius, F. Chem. Soc. Rev. 2023, 52, 4996.
	(e) Yang, Z.-Y.; Luo, H.; Zhang, M.; Wang, X.-C. ACS Catal. 2021, 11, 10824.
	(f) Wagener, T.; Lückemeier, L.; Daniliuc, C. G.; Glorius, F. Angew. Chem., Int. Ed. 2021, 60, 6425.
	(g) Zhang, X.; Ling, L.; Luo, M.; Zeng, X. Angew. Chem., Int. Ed. 2019, 58, 16785.
	(h) Chen, F.; Li, W.; Sahoo, B.; Kreyenschulte, C.; Agostini, G.; Lund, H.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2018, 130, 14696.
	(i) Cai, X.-F.; Huang, W.-X.; Chen, Z.; Zhou, Y.-G. Chem. Commun. 2014, 50, 9588.
[9]	Welin, E. R.; Ngamnithiporn, A.; Klatte, M.; Lapointe, G.; Pototschnig, G. M.; McDermott, M. S. J.; Conklin, D.; Gilmore, C. D.; Tadross, P. M.; Haley, C. K.; Negoro, K.; Glibstrup, E.; Grünanger, C. U.; Allan, K. M.; Virgil, S. C.; Slamon, D. J.; Stoltz, B. M. Science 2018, 363, 270.
[10]	(a) Liu, X.; Lou, M.; Bai, S.; Sun, G.; Qi, X. J. Org. Chem. 2022, 87, 5199.
	(b) Han, S.; Lou, M.; Qi, X. Synlett 2023, 35, 586.
	(c) Lou, M.; Liu, X.; Han, S.; Bai, S.; Qi, X. Chem. Commun. 2024, 60, 3842.
[11]	Colomer, I.; Chamberlain, A. E. R.; Haughey, M. B.; Donohoe, T. J. Nat. Rev. Chem. 2017, 1, 1.
[12]	McNulty, J.; Nair, J. J.; Little, J. R. L.; Brennan, J. D.; Bastida, J. Bioorg. Med. Chem. Lett. 2010, 20, 5290.
[13]	Hao, B.; Shen, S.-F.; Zhao, Q.-J. Molecules 2013, 18, 2458.
[14]	(a) Liu, X.-S.; Jiang, J.; Jiao, X.-Y.; Wu, Y.-E.; Lin, J.-J.; Cai, Y.-M. Cancer Lett. 2009, 274, 16.
	(b) Lamoral-Theys, D.; Andolfi, A.; Van Goietsenoven, G.; Cimmino, A.; Le Calvé, B.; Wauthoz, N.; Mégalizzi, V.; Gras, T.; Bruyère, C.; Dubois, J.; Mathieu, V.; Kornienko, A.; Kiss, R.; Evidente, A. J. Med. Chem. 2009, 52, 6244.
	(c) Wang, P.; Yuan, H.-H.; Zhang, X.; Li, Y.-P.; Shang, L.-Q.; Yin, Z. Molecules 2014, 19, 2469.
[15]	(a) Xiao, J.; Zhou, G. H.; Zhou, A. X.; Ji, C. B. Chem. Biodiversity 2022, 19, e202200410.
	(b) Bautista, D. D.; Vilchis Reyes, M. A.; Blé González, E. A.; Bugarin, A. Eur. J. Org. Chem. 2023, 26, e202300404.
	(c) Yoshizaki, H.; Satoh, H.; Sato, Y.; Nukui, S.; Shibasaki, M.; Mori, M. J. Org. Chem. 1995, 60, 2016.
	(d) Ikeda, M.; Ohtani, S.; Sato, T.; Ishibashi, H. Synthesis 1998, 1998, 1803.
	(e) Banwell, M. G.; Harvey, J. E.; Hockless, D. C. R. J. Org. Chem. 2000, 65, 4241.
	(f) Dong, L.; Xu, Y.-J.; Cun, L.-F.; Cui, X.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. Org. Lett. 2005, 7, 4285.
	(g) Hong, B. C.; Nimje, R. Y.; Wu, M. F.; Sadani, A. A. Eur. J. Org. Chem. 2008, 2008, 1449.
	(h) El Bialy, S. A. A. Nat. Prod. Res. 2008, 22, 1176.
	(i) Wang, Y.; Luo, Y.-C.; Zhang, H.-B.; Xu, P.-F. Org. Biomol. Chem. 2012, 10, 8211.
	(j) Li, G.; Xie, J. H.; Hou, J.; Zhu, S. F.; Zhou, Q. L. Adv. Synth. Catal. 2013, 355, 1597.
	(k) Rana, N. K.; Huang, H.; Zhao, J. C. G. Angew. Chem., Int. Ed. 2014, 53, 7619.
	(l) Sun, Z.; Zhou, M.; Li, X.; Meng, X.; Peng, F.; Zhang, H.; Shao, Z. Chem. Eur. J. 2014, 20, 6112.
	(m) Meng, X.-L.; Liu, T.; Sun, Z.-W.; Wang, J.-C.; Peng, F.-Z.; Shao, Z.-H. Org. Lett. 2014, 16, 3044.
	(n) Nishimura, K.; Fukuyama, N.; Yasuhara, T.; Yamashita, M.; Sumiyoshi, T.; Yamamoto, Y.; Yamada, K.-i.; Tomioka, K. Tetrahedron 2015, 71, 7222.
	(o) Chen, Y. J.; Cai, S. L.; Wang, C. C.; Cheng, J. D.; Kramer, S.; Sun, X. W. Chem. Asian J. 2017, 12, 1309.
	(p) Iida, H.; Yuasa, Y.; Kibayashi, C. J. Am. Chem. Soc. 1978, 100, 3598.
	(q) Padwa, A.; Brodney, M. A.; Lynch, S. M. J. Org. Chem. 2001, 66, 1716.
	(r) Miranda, L. D.; Zard, S. Z. Org. Lett. 2002, 4, 1135.
	(s) Zhang, H.; Shao, Z.; Chen, J.; Huang, R.; Wang, C.; Li, L. Synlett 2003, 2228.
	(t) Gao, S.; Tu, Y. Q.; Song, Z.; Wang, A.; Fan, X.; Jiang, Y. J. Org. Chem. 2005, 70, 6523.
	(u) Jung, Y.-G.; Lee, S.-C. L.; Cho, H.-K.; Darvatkar, N. B.; Song, J.-Y.; Cho, C.-G. Org. Lett. 2013, 15, 132.
	(v) Liu, D.; Ai, L.; Li, F.; Zhao, A.; Chen, J.; Zhang, H.; Liu, J. Org. Biomol. Chem. 2014, 12, 3191.
	(w) Yu, W. L.; Nunns, T.; Richardson, J.; Booker-Milburn, K. I. Org. Lett. 2018, 20, 1272.
	(x) Rocaboy, R.; Dailler, D.; Baudoin, O. Org. Lett. 2018, 20, 772.
	(y) Wilson, K. B.; Nedzbala, H. S.; Simpson, S. R.; Ericson, M. N.; Westendorff, K. S.; Chordia, M. D.; Dickie, D. A.; Harman, W. D. Helv. Chim. Acta 2021, 104, e2100103.

Entry	Solvent	Pd/C (mol%)	T/℃	t/h	9-1∶9-2∶9-3∶9-4^b
1	HFIP	1.3	25	20	1.0∶0.2∶1.0∶0
2	HFIP	2.5	25	23	0∶0∶1.0∶0.4
3	HFIP	2.5	60	24	0∶0∶0.9∶1.0
4^c	HFIP/TFA, V∶V=3∶1	6.3	25	27	0∶0∶0∶1.0
5^c	HFIP/TFA, V∶V=3∶1	6.3	60	12	0∶0∶0∶1.0
6	HFIP/TFA, V∶V=3∶1	2.5	60	24	0∶0∶0∶1.0
7	HFIP/TFA, V∶V=3∶1	2.5	25	24	0∶1.0∶0∶0.3
8	HFIP/TFA, V∶V=3∶1	1.3	60	16	0∶1.0∶0∶1.0
9	HFIP/TFA, V∶V=1∶1	1.3	25	18	0∶1.0∶0∶0
10	HFIP/TFA, V∶V=3∶1	2.5	25	22	0∶1.0∶0∶0.4
11	HFIP/HOAc, V∶V=3∶1	2.5	60	24	Messy
12	HFIP/HOAc, V∶V=3∶1	2.5	25	24	0∶0.7∶1.0∶0
13	HFIP/HOAc, V∶V=1∶1	2.5	25	22	0.5∶0.4∶1.0∶0
14	MeOH/TFA, V∶V=1∶1	2.5	25	22	0.3∶1.0∶0:0.4

Entry	Solvent	Pd/C (mol%)	T/℃	t/h	9-1∶9-2∶9-3∶9-4^b
1	HFIP	1.3	25	20	1.0∶0.2∶1.0∶0
2	HFIP	2.5	25	23	0∶0∶1.0∶0.4
3	HFIP	2.5	60	24	0∶0∶0.9∶1.0
4^c	HFIP/TFA, V∶V=3∶1	6.3	25	27	0∶0∶0∶1.0
5^c	HFIP/TFA, V∶V=3∶1	6.3	60	12	0∶0∶0∶1.0
6	HFIP/TFA, V∶V=3∶1	2.5	60	24	0∶0∶0∶1.0
7	HFIP/TFA, V∶V=3∶1	2.5	25	24	0∶1.0∶0∶0.3
8	HFIP/TFA, V∶V=3∶1	1.3	60	16	0∶1.0∶0∶1.0
9	HFIP/TFA, V∶V=1∶1	1.3	25	18	0∶1.0∶0∶0
10	HFIP/TFA, V∶V=3∶1	2.5	25	22	0∶1.0∶0∶0.4
11	HFIP/HOAc, V∶V=3∶1	2.5	60	24	Messy
12	HFIP/HOAc, V∶V=3∶1	2.5	25	24	0∶0.7∶1.0∶0
13	HFIP/HOAc, V∶V=1∶1	2.5	25	22	0.5∶0.4∶1.0∶0
14	MeOH/TFA, V∶V=1∶1	2.5	25	22	0.3∶1.0∶0:0.4

吲哚发散性氢化及其在(±)-α-和γ-Lycoranes的全合成中的应用