Total Synthesis of Metaphanine and Oxoepistephamiersine
Ya-Kui Sun
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
These authors contributed equally to this work.
Search for more papers by this authorJin-Bao Qiao
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
These authors contributed equally to this work.
Search for more papers by this authorYu-Meng Xin
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorQin Zhou
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorZhi-Hua Ma
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorHui Shao
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorCorresponding Author
Yu-Ming Zhao
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorYa-Kui Sun
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
These authors contributed equally to this work.
Search for more papers by this authorJin-Bao Qiao
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
These authors contributed equally to this work.
Search for more papers by this authorYu-Meng Xin
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorQin Zhou
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorZhi-Hua Ma
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorHui Shao
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorCorresponding Author
Yu-Ming Zhao
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119 China
Search for more papers by this authorAbstract
Herein, we report a concise and divergent synthesis of the complex hasubanan alkaloids metaphanine and oxoepistephamiersine from commercially available and inexpensive cyclohexanedione monoethylene acetal. Our synthesis features a palladium-catalyzed cascade cyclization reaction to set the tricyclic carbon framework of the desired molecules, a regioselective Baeyer–Villiger oxidation followed by a MeNH2 triggered skeletal reorganization cascade to construct the benzannulated aza[4.4.3]propellane, and a strategically late-stage regio-/diastereoselective oxidative annulation of sp3 C−H bond to form the challenging THF ring system and hemiketal moiety in a single step. In addition, a highly enantioselective alkylation of cyclohexanedione monoethylene acetal paved the way for the asymmetric synthesis of target molecular.
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References
- 1
- 1aM. Matsui, in The Alkaloids: Chemistry and Pharmacology, Vol. 33 (Ed.: A. Brossi), Academic Press, New York, 1988, p. 307;
- 1bS. M. King, S. B. Herzon, in The Alkaloids: Chemistry and Biology, Vol. 73 (Ed.: H.-J. Knölker), Academic Press, Burlington, 2014, p. 161.
- 2
- 2aH. Kondo, M. Satomi, T. Odera, Annu. Rep. Itsuu Lab. 1951, 2, 35;
- 2bM. Tomita, T. Ibuka, Y. Inubushi, Y. Watanabe, M. Matsui, Tetrahedron Lett. 1964, 5, 2937.
10.1016/0040-4039(64)83066-5 Google Scholar
- 3
- 3aD. K. Semwal, U. Rawat, Planta Med. 2009, 75, 378;
- 3bA. R. Carroll, T. Arumugan, J. Redburn, A. Ngo, G. P. Guymer, P. I. Forster, R. J. Quinn, J. Nat. Prod. 2010, 73, 988.
- 4
- 4aM. Tomita, T. Ibuka, Y. Inubuahi, K., Tetrahedron Lett. 1964, 5, 3605;
- 4bM.-H. Yan, P. Cheng, Z.-Y. Jiang, Y.-B. Ma, X.-M. Zhang, F.-X. Zhang, L.-M. Yang, Y.-T. Zheng, J.-J. Chen, J. Nat. Prod. 2008, 71, 760;
- 4cM. Matsui, Y. Yamamura, T. Takebayashi, K. Iwaki, Y. Takami, K. Kunitake, F. Koga, S. Urasaki, Y. Watanabe, J. Nat. Prod. 1984, 47, 858.
- 5T. Ibuka, K. Tanaka, Y. Inubushi, Tetrahedron Lett. 1970, 11, 4811.
10.1016/S0040-4039(00)89353-3 Google Scholar
- 6For selected recent synthetic studies of hasubanan alkaloids, see:
- 6aS. B. Jones, L. He, S. L. Castle, Org. Lett. 2006, 8, 3757;
- 6bT. X. Nguyen, Y. Kobayashi, J. Org. Chem. 2008, 73, 5536;
- 6cD. K. Nielsen, L. L. Nielsen, S. B. Jones, L. Toll, M. C. Asplund, S. L. Castle, J. Org. Chem. 2009, 74, 1187;
- 6dF. Li, S. S. Tartakoff, S. L. Castle, J. Am. Chem. Soc. 2009, 131, 6674;
- 6eK. V. Chuang, R. Navarro, S. E. Reisman, Angew. Chem. Int. Ed. 2011, 50, 9447;
- 6fP. Magnus, C. Seipp, Org. Lett. 2013, 15, 4870;
- 6gS. M. King, N. A. Calandra, S. B. Herzon, Angew. Chem. Int. Ed. 2013, 52, 3642;
- 6hN. A. Calandra, S. M. King, S. B. Herzon, J. Org. Chem. 2013, 78, 10031;
- 6iS. M. King, S. B. Herzon, J. Org. Chem. 2014, 79, 8937;
- 6jG. Volpin, N. A. Vepřek, A. B. Bellan, D. Trauner, Angew. Chem. Int. Ed. 2017, 56, 897;
- 6kN. Hartrampf, N. Winter, G. Pupo, B. M. Stoltz, D. Trauner, J. Am. Chem. Soc. 2018, 140, 8675;
- 6lS. Tan, F. Li, S. Park, S. Kim, Org. Lett. 2019, 21, 292;
- 6mG. Li, Q. Wang, J. Zhu, Nat. Commun. 2021, 12, 36;
- 6nM. Odagi, T. Matoba, K. Nagasawa, J. Org. Chem. 2022, 87, 1065;
- 6oB. Yang, G. Li, Q. Wang, J. Zhu, J. Am. Chem. Soc. 2023, 145, 5001.
- 7
- 7aS. B. Herzon, N. A. Calandra, S. M. King, Angew. Chem. Int. Ed. 2011, 50, 8863;
- 7bM. Odagi, T. Matoba, K. Hosoya, K. Nagasawa, J. Am. Chem. Soc. 2021, 143, 2699;
- 7cS. Ding, Y. Shi, B. Yang, M. Hou, H. He, S. Gao, Angew. Chem. Int. Ed. 2023, 62, No. e202214873.
- 8
- 8aL. Xu, C. Wang, Z. Gao, Y.-M. Zhao, J. Am. Chem. Soc. 2018, 140, 5653;
- 8bH. Shao, X. Gao, Z.-T. Wang, Z. Gao, Y.-M. Zhao, Angew. Chem. Int. Ed. 2020, 59, 7419.
- 9
- 9aY. Ishihara, P. S. Baran, Synlett 2010, 12, 1733;
- 9bT. Newhouse, P. S. Baran, Angew. Chem. Int. Ed. 2011, 50, 3362;
- 9cY. Kanda, Y. Ishihara, N. C. Wilde, P. S. Baran, J. Org. Chem. 2020, 85, 10293.
- 10Y. Zhang, Y.-K. Sun, Y.-P. Chang, H. Shao, Y.-M. Zhao, Chem. Commun. 2021, 57, 7023.
- 11
- 11aS. K. Singh, A. Das, Phys. Chem. Chem. Phys. 2015, 17, 9596;
- 11bR. W. Newberry, R. T. Raines, Acc. Chem. Res. 2017, 50, 1838.
- 12Deposition numbers 2254864 (for 6), 2254867 (for 13), 2254866 (for 16), 2254865 (for 19), and 2289417 (for (+)-9) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.
- 13T. Diao, D. Pun, S. Stahl, J. Am. Chem. Soc. 2023, 145, 5001.
- 14For selected recent examples of hydroxyl-directed oxidative THF ring formation in natural product total synthesis, see:
- 14aM. E. McCallum, C. M. Rasik, J. L. Wood, M. K. Brown, J. Am. Chem. Soc. 2016, 138, 2437;
- 14bM. L. Condakes, K. Hung, S. J. Harwood, T. J. Maimone, J. Am. Chem. Soc. 2017, 139, 17783;
- 14cM. Haider, G. Sennari, A. Eggert, R. Sarpong, J. Am. Chem. Soc. 2021, 143, 2710;
- 14dT. Hwang, J. P. Tuccinardi, A. A. Beard, A. C. Jackson, M. J. Jung, J. L. Wood, Angew. Chem. Int. Ed. 2022, 61, e202210821;
- 14eZ. Qing, P. Mao, T. Wang, H. Zhai, J. Am. Chem. Soc. 2022, 144, 10640.
- 15For selected recent examples, see:
- 15aG. Barbe, A. B. Charette, J. Am. Chem. Soc. 2008, 130, 18;
- 15bY. Motoyama, M. Aoki, N. Takaoka, R. Aoto, H. Nagashima, Chem. Commun. 2009, 1574;
- 15cP.-Q. Huang, H. Geng, Org. Chem. Front. 2015, 2, 150;
- 15dF. Tinnis, A. Volkov, T. Slagbrand, H. Adolfsson, Angew. Chem. Int. Ed. 2016, 55, 4562;
- 15eB. J. Simmons, M. Hoffmann, J. Hwang, M. K. Jackl, N. K. Garg, Org. Lett. 2017, 19, 1910;
- 15fL. J. Donnelly, J.-C. Berthet, T. Cantat, Angew. Chem. Int. Ed. 2022, 61, e202206170.
- 16For metal-free directed hydroboration of olefin, see:
- 16aM. Scheideman, G. Wang, E. Vedejs, J. Am. Chem. Soc. 2008, 130, 8669;
- 16bG. Wang, E. Vedejs, Org. Lett. 2009, 11, 1059;
- 16cM. G. Tabor, R. A. Shenvi, Org. Lett. 2015, 17, 5776.
- 17
- 17aM. Sugiura, T. Nakai, Angew. Chem. Int. Ed. 1997, 36, 2366;
- 17bA. Yanagisawa, T. Touge, T. Arai, Angew. Chem. Int. Ed. 2005, 44, 1546;
- 17cC. H. Cheon, H. Yamamoto, J. Am. Chem. Soc. 2008, 130, 9246.
- 18
- 18aD. Enders, A. Nuhring, J. Rünsink, Chirality 2000, 12, 374;
10.1002/(SICI)1520-636X(2000)12:5/6<374::AID-CHIR13>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- 18bA. Job, C. F. Janeck, W. Bettray, R. Peters, D. Enders, Tetrahedron 2002, 58, 2253.
- 19In contrast, the N-amino cyclic carbamates (ACCs) based chiral auxiliary afforded moderate enantioselectivity (for the details, see SI).
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