A Concise Total Synthesis of (−)-Berkelic Acid
Prof. Dr. Hong-Gang Cheng
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
These authors contributed equally to this work.
Search for more papers by this authorZhenjie Yang
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
These authors contributed equally to this work.
Search for more papers by this authorRuiming Chen
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorLiming Cao
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorWen-Yan Tong
College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082 China
Search for more papers by this authorQiang Wei
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorQingqing Wang
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorChenggui Wu
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Shuanglin Qu
College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Qianghui Zhou
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
The Institute for Advanced Studies, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorProf. Dr. Hong-Gang Cheng
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
These authors contributed equally to this work.
Search for more papers by this authorZhenjie Yang
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
These authors contributed equally to this work.
Search for more papers by this authorRuiming Chen
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorLiming Cao
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorWen-Yan Tong
College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082 China
Search for more papers by this authorQiang Wei
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorQingqing Wang
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorChenggui Wu
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Shuanglin Qu
College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Qianghui Zhou
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 China
The Institute for Advanced Studies, Wuhan University, Wuhan, 430072 China
Search for more papers by this authorDedicated to the 70th anniversary of Shanghai Institute of Organic Chemistry
Abstract
Reported here is a concise total synthesis of (−)-berkelic acid in eight linear steps. This synthesis features a Catellani reaction/oxa-Michael cascade for the construction of the isochroman scaffold, a one-pot deprotection/spiroacetalization operation for the formation of the tetracyclic core structure, and a late-stage Ni-catalyzed reductive coupling for the introduction of the lateral chain. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process. Stereocontrol of the intriguing deprotection/spiroacetalization process is supported by DFT calculations.
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References
- 1A. A. Stierle, D. B. Stierle, K. Kelly, J. Org. Chem. 2006, 71, 5357–5360.
- 2
- 2aP. Buchgraber, T. N. Snaddon, C. Wirtz, R. Mynott, R. Goddard, A. Fürstner, Angew. Chem. Int. Ed. 2008, 47, 8450–8454; Angew. Chem. 2008, 120, 8578–8582;
- 2bT. N. Snaddon, P. Buchgraber, S. Schulthoff, C. Wirtz, R. Mynott, A. Fürstner, Chem. Eur. J. 2010, 16, 12133–12140.
- 3
- 3aJ. Zhou, B. B. Snider, Org. Lett. 2007, 9, 2071–2074;
- 3bX. Wu, J. Zhou, B. B. Snider, Angew. Chem. Int. Ed. 2009, 48, 1283–1286; Angew. Chem. 2009, 121, 1309–1312;
- 3cX. Wu, J. Zhou, B. B. Snider, J. Org. Chem. 2009, 74, 6245–6252.
- 4
- 4aC. F. Bender, F. K. Yoshimoto, C. L. Paradise, J. K. De Brabander, J. Am. Chem. Soc. 2009, 131, 11350–11352;
- 4bC. F. Bender, C. L. Paradise, V. M. Lynch, F. K. Yoshimoto, J. K. De Brabander, Tetrahedron 2018, 74, 909–919.
- 5
- 5aF. J. Fañanás, A. Mendoza, T. Arto, B. Temelli, F. Rodriguez, Angew. Chem. Int. Ed. 2012, 51, 4930–4933; Angew. Chem. 2012, 124, 5014–5017;
- 5bT. Arto, A. Mendoza, F. J. Fañanás, F. Rodríguez, in Strategies and Tactics in Organic Synthesis (Ed.: M. Harmata), Elsevier, Amsterdam, 2014, pp. 33–49;
10.1016/B978-0-12-417185-5.00002-8 Google Scholar
- 5cT. Arto, I. S. de Santa-María, M.-D. Chiara, F. J. Fañanás, F. Rodríguez, Eur. J. Org. Chem. 2016, 5876–5880.
- 6
- 6aY. Huang, T. R. Pettus, Synlett 2008, 9, 1353–1356;
- 6bT. A. Wenderski, M. A. Marsini, T. R. Pettus, Org. Lett. 2011, 13, 118–121.
- 7
- 7aZ. E. Wilson, M. A. Brimble, Org. Biomol. Chem. 2010, 8, 1284–1286;
- 7bM. C. McLeod, Z. E. Wilson, M. A. Brimble, Org. Lett. 2011, 13, 5382–5385;
- 7cM. A. Brimble, I. Haym, J. Sperry, D. P. Furkert, Org. Lett. 2012, 14, 5820–5823;
- 7dM. C. McLeod, Z. E. Wilson, M. A. Brimble, J. Org. Chem. 2012, 77, 400–416.
- 8The recent bioactivity studies of (−)-berkelic acid (see Refs. [3c], [4b] and [5c]) are inconsistent with the originally reported ones (see Ref. [1]), which deserves further systematic studies.
- 9For selected reviews, see:
- 9aT. Moragas, A. Correa, R. Martin, Chem. Eur. J. 2014, 20, 8242–8258;
- 9bC. E. Knappke, S. Grupe, D. Gartner, M. Corpet, C. Gosmini, A. Jacobi von Wangelin, Chem. Eur. J. 2014, 20, 6828–6842;
- 9cD. A. Everson, D. J. Weix, J. Org. Chem. 2014, 79, 4793–4798;
- 9dJ. Gu, X. Wang, W. Xue, H. Gong, Org. Chem. Front. 2015, 2, 1411–1421;
- 9eX. Wang, Y. Dai, H. Gong, Top. Curr. Chem. 2016, 374, 43; For selected recent examples, see:
- 9fA. C. Wotal, D. J. Weix, Org. Lett. 2012, 14, 1476–1479;
- 9gF. Wu, W. Lu, Q. Qian, Q. Ren, H. Gong, Org. Lett. 2012, 14, 3044–3047;
- 9hH. Yin, C. Zhao, H. You, K. Lin, H. Gong, Chem. Commun. 2012, 48, 7034–7036;
- 9iA. H. Cherney, N. T. Kadunce, S. E. Reisman, J. Am. Chem. Soc. 2013, 135, 7442–7445;
- 9jC. Zhao, X. Jia, X. Wang, H. Gong, J. Am. Chem. Soc. 2014, 136, 17645–17651;
- 9kX. Jia, X. Zhang, Q. Qian, H. Gong, Chem. Commun. 2015, 51, 10302–10305;
- 9lX. Lu, Y. Wang, B. Zhang, J. J. Pi, X. X. Wang, T. J. Gong, B. Xiao, Y. Fu, J. Am. Chem. Soc. 2017, 139, 12632–12637;
- 9mS. Z. Sun, M. Borjesson, R. Martin-Montero, R. Martin, J. Am. Chem. Soc. 2018, 140, 12765–12769;
- 9nL. Luo, X. Y. Zhai, Y. W. Wang, Y. Peng, H. Gong, Chem. Eur. J. 2019, 25, 989–992;
- 9oF. F. Pan, P. Guo, C. L. Li, P. Su, X. Z. Shu, Org. Lett. 2019, 21, 3701–3705;
- 9pJ. Zhuo, Y. Zhang, Z. Li, C. Li, ACS Catal. 2020, 10, 3895–3903;
- 9qJ. Wang, M. E. Hoerrner, M. P. Watson, D. J. Weix, Angew. Chem. Int. Ed. 2020, 59, 13484–13489; Angew. Chem. 2020, 132, 13586–13591.
- 10
- 10aH.-G. Cheng, C. Wu, H. Chen, R. Chen, G. Qian, Z. Geng, Q. Wei, Y. Xia, J. Zhang, Y. Zhang, Q. Zhou, Angew. Chem. Int. Ed. 2018, 57, 3444–3448; Angew. Chem. 2018, 130, 3502–3506;
- 10bC. Wu, H.-G. Cheng, Q. Zhou, Synlett 2020, 31, 829–837.
- 11For seminal work, see:
- 11aM. Catellani, F. Frignani, A. Rangoni, Angew. Chem. Int. Ed. Engl. 1997, 36, 119–122; Angew. Chem. 1997, 109, 142–145; For selected total synthesis examples applying the Catellani-type reaction as the key step, see:
- 11bL. Jiao, E. Herdtweck, T. Bach, J. Am. Chem. Soc. 2012, 134, 14563–14572;
- 11cH. Weinstabl, M. Suhartono, Z. Qureshi, M. Lautens, Angew. Chem. Int. Ed. 2013, 52, 5305–5308; Angew. Chem. 2013, 125, 5413–5416;
- 11dM. Mizutani, S. Yasuda, C. Mukai, Chem. Commun. 2014, 50, 5782–5785;
- 11eK. Zhao, S. Xu, C. Pan, X. Sui, Z. Gu, Org. Lett. 2016, 18, 3782–3785;
- 11fS.-Z. Jiang, X.-Y. Zeng, X. Liang, T. Lei, K. Wei, Y.-R. Yang, Angew. Chem. Int. Ed. 2016, 55, 4044–4048; Angew. Chem. 2016, 128, 4112–4116;
- 11gT. Xiao, Z.-T. Chen, L.-F. Deng, D. Zhang, X.-Y. Liu, H. Song, Y. Qin, Chem. Commun. 2017, 53, 12665–12667;
- 11hF. Liu, Z. Dong, J. Wang, G. Dong, Angew. Chem. Int. Ed. 2019, 58, 2144–2148; Angew. Chem. 2019, 131, 2166–2170;
- 11iS. Gao, G. Qian, H. Tang, Z. Yang, Q. Zhou, ChemCatChem 2019, 11, 5762–5765;
- 11jK. Yoshida, K. Okada, H. Ueda, H. Tokuyama, Angew. Chem. Int. Ed. 2020, 59, 23089–23093; Angew. Chem. 2020, 132, 23289–23293.
- 12F. Björkling, J. Boutelje, S. Gatenbeck, K. Hult, T. Norin, P. Szmulik, Tetrahedron 1985, 41, 1347–1352.
- 13P. Dewi-Wülfing, J. Gebauer, S. Blechert Synlett 2006, 0487–0489.
- 14For the gram-scale preparation of building blocks 7 and 8, please see the Supporting Information (SI) for details.
- 15K. Yu, Z. N. Yang, C. H. Liu, S. Q. Wu, X. Hong, X. L. Zhao, H. Ding, Angew. Chem. Int. Ed. 2019, 58, 8556–8560; Angew. Chem. 2019, 131, 8644–8648.
- 16DFT calculations were performed by Gaussian program under the level of M06-2X/def2-TZVPP-SMD(MeOH)//B3LYP-D3(BJ)/def2-SVP. See the SI for computational details.
- 17For related calculation results, please see the SI for details.
- 18Chiral acyl chloride 2 is readily prepared through the enzymatic hydrolysis of the known prochiral diester 5 (referring to Björkling's work (Ref. [11])) and a following reaction with SOCl2. See the SI for experimental details.
- 19The 22R-diastereomer of (−)-bekelic acid methyl ester 17 and other diastereoisomers were also formed through this reductive coupling protocol (detected by crude 1H NMR and HRMS). However, we failed to obtain the pure sample for characterization owing to the contamination of some unidentified impurities with a similar polarity.
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