Enantioselective Construction of 5‐6‐5 Tricyclic Lactone Framework Bearing a Quaternary Bridgehead Carbon via Rh‐Catalyzed Asymmetric [2+2+2] Cycloaddition of Enediynes

[1] a) K. W. Quasdorf, L. E. Overman, Nature 2014, 516, 181–191; b) X.-P. Zeng, Z.-Y. Cao, Y.-H. Wang, F. Zhou, J. Zhou, Chem. Rev. 2016, 116, 7330–7396; c) P.- W. Xu, J.-S. Yu, C. Chen, Z.-Y. Cao, F. Zhou, J. Zhou, ACS Catal. 2019, 9, 1820–1882.

[2] a) Y. Liu, S.-J. Han, W.-B. Liu, B. M. Stoltz, Acc. Chem. Res. 2015, 48, 740–751; b) R. Long, J. Huang, J. Gong, Z. Yang, Nat. Prod. Rep. 2015, 32, 1584–1601; c) M. Büschleb, S. Dorich, S. Hanessian, D. Tao, K. B. Schenthal, L. E. Overman, Angew. Chem. Int. Ed. 2016, 55, 4156–4186; d) C. Li, S. S. Ragab, G. Liu, W. Tang, Nat. Prod. Rep. 2020, 37, 276–292.

[3] a) N. P. Sahu, K. Koike, S. Banerjee, B. Achari, Z. Jia, T. Nikaido, Tetrahedron Lett. 1997, 38, 8405–8408; b) W. J. Robbins, F. Kavanagh, A. Herver, Proc. Natl. Acad. Sci. U. S. A. 1947, 33, 171–176; c) J. Grandjean, R. Huls, Tetrahedron Lett. 1974, 1893–1895; d) C. Lv, X. Yan, Q. Tu, Y. Di, C. Yuan, X. Fang, Y. Ben-David, L. Xia, J. Gong, Y. Shen, Z. Yang, X. Hao, Angew. Chem. Int. Ed. 2016, 55, 7539–7543; Angew. Chem. 2016, 128, 7665–7669.

[4] a) M. Kubo, C. Okada, J.-M. Huang, K. Harada, H. Hioki, Y. Fukuyama, Org. Lett. 2009, 11, 5190–5193; b) R. A. Shenvi, Nat. Prod. Rep. 2016, 33, 535–539; c) J. M. Witkin, R. A. Shenvi, X. Li, S. D. Gleason, J. Weiss, D. Morrow, J. T. Catow, M. Wakulchik, M. Ohtawa, H. H. Lu, M. D. Martinez, J. M. Schkeryantz, T. S. Carpenter, F. C. Lightstone, R. Cerne, Biochem. Pharmacol. 2018, 155, 61–70; d) M. Shoji, M. Ueda, M. Nishioka, H. Minato, M. Seki, K. Harada, M. Kubo, Y. Fukuyama, Y. Suzuki, E. Aoyama, M. Takigawa, T. Kuzuhara, Biochem. Biophy. Res. Commun. 2019, 519, 309–315; e) Y. Fukuyama, M. Kubo, K. Harada, J. Nat. Med. 2020, 74, 648–671.

[5] a) Y. S. Cho, D. A. Carcache, Y. Tian, Y.-M. Li, S. J. Danishefsky, J. Am. Chem. Soc. 2004, 126, 14358– 14359; b) D. A. Carcache, Y. S. Cho, Z. Hua, Y. Tian, Y.-M. Li, S. J. Danishefsky, J. Am. Chem. Soc. 2006, 128, 1016–1022; c) L. Trzoss, J. Xu, M. H. Lacoske, W. C. Mobley, E. A. Theodorakis, Chem. Eur. J. 2013, 19, 6398–6408.

[6] For recent reviews involving transition-metal-catalyzed [2+2+2] cycloaddition reactions, see: a) K. Tanaka, Synlett 2007, 1977–1993; b) T. Shibata, K. Tsuchikama, Org. Biomol. Chem. 2008, 6, 1317–1323; c) V. Michelet, P. Y. Toullec, J.-P. Genêt, Angew. Chem. Int. Ed. 2008, 47, 4268–4315; Angew. Chem. 2008, 120, 4338–4386; d) Y. Shibata, K. Tanaka, Synthesis 2012, 44, 323–350; e) K. Tanaka, Chem. Asian J. 2009, 4, 508–518; e) M. Amatore and C. Aubert, Eur. J. Org. Chem. 2015, 265– 286; f) G. Domínguez, J. Pérez-Castells, Chem. Eur. J. 2016, 22, 6720–6739; g) Y. Yamamoto, Tetrahedron Lett. 2017, 58, 3787–3794; h) A. Pla-Quintana, A. Roglans, Asian J. Org. Chem. 2018, 7, 1706–1718; i) A. Roglans, A. Pla-Quintana, M. Solà, Chem. Rev. 2021, 121, 1894–1979.

[7] M. Shibuya, T. Sudoh, T. Kawamura, Y. Yamamoto, Org. Biomol. Chem. 2015, 13, 5862–5866.

[8] T. Kawamura, H. Moriya, M. Shibuya, Y. Yamamoto, J. Org. Chem. 2019, 84, 12508–12519.

[9] a) K. Tanaka, G. Nishida, H. Sagae, M. Hirano, Synlett 2007, 1426–1430; b) T. Shibata, H. Kurokawa, K. Kanda, J. Org. Chem. 2007, 72, 6521–6525; c) T. León, M. Parera, A. Roglans, A. Riera, X. Verdaguer, Angew. Chem. Int. Ed. 2012, 51, 6951–6955; Angew. Chem. 2012, 124, 7057–7061.

[10] For selected examples of asymmetric [2+2+2] cycloadditions to construct a quaternary bridgehead stereocenter, see: a) T. Shibata, Y. Arai, Y. Tahara, Org. Lett. 2005, 7, 4955–4957; b) T. Shibata, Y. Tahara, J. Am. Chem. Soc. 2006, 128, 11766–11767; c) H. Sagae, K. Noguchi, M. Hirano, K. Tanaka, Chem. Commun. 2008, 3804–3806; d) K. Tanaka, Y. Otake, K. Noguchi, M. Hirano, Angew. Chem. Int. Ed. 2008, 47, 1312–1316; Angew. Chem. 2008, 120, 1332–1336; e) T. Suda, K. Noguchi, K. Tanaka, Angew. Chem. Int. Ed. 2011, 50, 4475–4479; Angew. Chem. 2011, 123, 4567–4571; f) A. T. Brusoe, E. J. Alexanian, Angew. Chem. Int. Ed. 2011, 50, 6596–6600; Angew. Chem. 2011, 123, 6726–6730; g) S. Suzuki, Y. Shibata, K. Tanaka, Chem. Eur. J. 2020, 26, 3698-3702.

[11] For selected examples of the synthesis of racemic tricyclic cyclohexadienes via transition-metal-catalyzed [2+2+2] cycloadditions, see: a) R. L. Halterman, K. P. C. Vollhardt, Organometallics 1988, 7, 883–892; b) Y. Yamamoto, S. Kuwabara, Y. Ando, H. Nagata, H. Nishiyama, K. Itoh, J. Org. Chem. 2004, 69, 6697–6705; c) A. Torrent, I. González, A. Pla-Quintana, A. Roglans, J. Org. Chem. 2005, 70, 2033–2041; d) S. Brun, L. Garcia, I. González, A. Torrent, A. Dachs, A. PlaQuintana, T. Parella, A. Roglans, Chem. Commun. 2008, 4339–4341; e) A. L. Jones, J. K. Snyder, J. Org. Chem. 2009, 74, 2907–2910; f) A. Geny, S. Gaudrel, F. Slowinski, M. Amatore, G. Chouraqui, M. Malacria, C. Aubert, V. Gandon, Adv. Synth. Catal. 2009, 351, 271– 275; g) A. L. Jones, J. K. Snyder, Org. Lett. 2010, 12, 1592–1595; h) A. Dachs, A. Pla-Quintana, T. Parella, M. Solà, A. Roglans, Chem. Eur. J. 2011, 17, 14493–14507; i) S. Ventre, C. Simon, F. Rekhroukh, M. Malacria, M. Amatore, C. Aubert, M. Petit, Chem. Eur. J. 2013, 19, 5830–5835.

[12] A mechanistic study for the RhCl(PPh3)3-catalyzed [2+2+2] cycloaddition of enediynes has been reported, see: A. Dachs, A. Roglans, M. Solà, Organometallics 2011, 30, 3151–3159.

[13] For selected examples involving the synthesis of chiral cyclohexadienes via the Rh-catalyzed enantioselective intermolecular [2+2+2] cycloadditions, see: a) P. A. Evans, K. W. Lai, J. R. Sawyer, J. Am. Chem. Soc. 2005, 127, 12466–12467; b) K. Tsuchikama, Y. Kuwata, T. Shibata, J. Am. Chem. Soc. 2006, 128, 13686–13687; c) P. A. Evans, J. R. Sawyer, P. A. Inglesby, Angew. Chem. Int. Ed. 2010, 49, 5746–5749; d) J. Hara, M. Ishida, M. Kobayashi, K. Noguchi, K. Tanaka, Angew. Chem. Int. Ed. 2014, 53, 2956–2959; Angew. Chem. 2014, 126, 3000–3003; e) Y. Aida, H. Sugiyama, H. Uekusa, Y. Shibata, K. Tanaka, Org. Lett. 2016, 18, 2672−2675; f) Y. Aida, Y. Shibata, K. Tanaka, J. Org. Chem. 2018, 83, 2617−2626; g) Q. Teng, W. Mao, D. Chen, Z. Wang, C.- H. Tung, Z. Xu, Angew. Chem. Int. Ed. 2020, 59, 2220– 2224; Angew. Chem. 2020, 132, 2240–2244.

[14] a) Y. Kishimoto, P. Eckerle, T. Miyake, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1994, 116, 12131–12132; b) K. Maeda, H. Goto, E. Yashima, Macromolecules 2001, 34, 1160–1164.

[15] a) P. J. Pye, K. Rossen, R. A. Reamer, N. N. Tsou, R. P. Volante, P. J. Reider, J. Am. Chem. Soc. 1997, 119, 6207−6208; b) H.-Y. Jang, F. W. Hughes, H. Gong, J. Zhang, J. S. Brodbelt, M. J. Krische, J. Am. Chem. Soc. 2005, 127, 6174−6175; c) L. A. Schwartz, M. Holmes, G. A. Brito, T. P. Gonçalves, J. Richardson, J. C. Ruble, K.-W. Huang, M. J. Krische, J. Am. Chem. Soc. 2019, 141, 2087−2096.

[16] CCDC-2063018 ((S)-4g) and 2063019 (7) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

[17] a) T. Yasui, T. Kikuchi, Y. Yamamoto, Chem. Commun. 2020, 56, 12865–12868; b) J. Nogami, Y. Tanaka, H. Sugiyama, H. Uekusa, A. Muranaka, M. Uchiyama, K. Tanaka, J. Am. Chem. Soc. 2020, 142, 9834−9842.

[18] a) L. Falivene, R. Credendino, A. Poater, A. Petta, L. Serra, R. Oliva, V. Scarano, L Cavallo, Organometallics 2016, 35, 2286–2293; b) L. Falivene, Z. Cao, A. Petta, L. Serra, A. Poater, R. Oliva, V. Scarano, L. Cavallo, Nat. Chem. 2019, 11, 872–879.