運用有機小分子進行不對稱催化之連鎖反應，為高效率建構多重鍵結與立體中心之策略。其中，含氧之多環結構，常見於天然物分子中並具廣泛的生物活性，有效建構高光學純度的多環含氧雜環化合物，在有機合成領域中備受重視。
本實驗室利用α,α-雙苯基脯胺醇矽醚類催化劑與酸性添加劑，進行共催化，促使α,β-不飽和醛類和2-(乙醯乙醯基)苯酚，於最佳化的條件下，進行 Michael/Acetalization/Hemiacetalization之連鎖反應，生成半縮醛產物，再進一步經由氯鉻酸吡啶鹽一鍋化的氧化方式，生成具有三個連續掌性中心之三環苯併二氫吡喃酮衍生物，有著優異的產率（up to 97% yield）及立體選擇性（>20:1 dr and up to 94% ee）。

The construction of highly complex scaffold with several stereogenic centers could be accomplished by organic small molecules in asymmetric domino reactions. The chromanone is one of common heterocyclic compounds in nature. In addition, their derivatives have been shown with a wide range of biological properties. Therefore, it’s important to develop effective methods to conduct a series of highly stereoselective compounds in organic asymmetric synthesis.
An efficient strategy has been disclosed to afford tricyclic chromanone derivatives by treating with α,β-unsaturated aldehydes and 2-(acetoacetyl)phenols in our laboratory. After extensive optimization studies, the treatment of 20 mol% of α,α- diphenyl-L-prolinol trimethyl silyl ether and benzoic acid would give the high level of optically pure product which were bearing 3 stereogenic centers. This reaction was proceeded through Michael/Acetalization/Hemiacetalization sequence, the hemiacetal products were then oxidized by PCC in one-pot manner to achieve lactone derivatives with outstanding chemical yields（up to 97%）and good stereoselectivies (>20:1 dr and up to 94% ee).

1.Nguyen, L. A.; He, H.; Chuong, P.-H. Int J Biomed Sci. 2006, 2, 85.
2.Bredig, G.; Fiske, W. S. Biochem. Z. 1912, 7.
3.(a) Pracejus, H. Justus Liebigs Ann. Chem. 1960, 634, 9.
(b) Pracejus, H.; Mätje, J. H. Prakt. Chem. 1964, 24, 195.
4.(a) Eder, U.; Sauer, G.; Wiechert, R. Angew. Chem. Int. Ed. 1971, 10, 496.
(b) Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1615.
5.(a) List, B.; Lerner, R. A.; Barbas III, C. F. J. Am. Chem. Soc. 2000, 122, 2395.
(b) List, B. Tetrahedron 2002, 58, 5573.
6.Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243.
7.(a) Oku, J.; Inoue, S. J. C. S. Chem.Comm. 1981, 229.
(b) Oku, J.-I.; Ito, N.; Inoue, S. Macromol. Chem. 1982, 183, 579.
8.(a) Juliá, S.; Guixer, J.; Masana, J.; Rocas J.; Colonna, S.; Annuziata, R.; Molinari, H. J. Chem. Soc., Perki Trans.,1982, 1, 1317.
(b) Juliá, S.; Masana, J.; Vega,J. C. Angew.Chem. Int. Ed. Engl. 1980, 19, 929.
9.Palumbo, C.; Guidotti, M. Science Open Research 2015
( DOI: 10.14293/S2199-1006.1.SOR-CHEM.AGZIIB.v3 )
10.(a) Seayad, J.; List, B. Org Biomol Chem. 2005, 3, 719.
(b) Bella ,M.; Gasperi, T. Synthesis. 2009, 10, 1583.
11.Doyle, A. G.; Jacobsen, E. N. Chem Rev. 2007, 107, 5713.
12.Knowles, R. R.; Jacobsen, E. N. PNAS 2010, 107, 20678.
13.(a) Vakulya, B.; Varga, S.; Csámpai, A.; Soós, T. Org Lett. 2005, 7, 1967.
(b) Schreiner, .P. R.; Wittkopp, A. Org Lett. 2002, 4, 217.
(c) Lattanzi, A. Adv Synth Catal. 2006, 348, 339.
(d) Reddy, B. V. S.; Reddy, S. M.; Swain, M.; Dudem, S.; Kalivendi, S. V.; Reddy C.S. RSC Adv. 2014, 4, 9107.
14.Jørgensen, K. A.; Johannsen, M.; Yao, S.; Audrain, H.; Thorhauge, J. Acc. Chem. Res. 1999, 32, 605.
15.Jensen, K. L.; Dickmeiss, G.; Jiang, H.; Albrecht, L.; Jørgensen, K. A. Acc. Chem. Res. 2012, 45, 248.
16.Juhl, K.; Jørgensen, K. A. J. Am. Chem. Soc. 2002, 124, 2420.
17.Jensen, K. B.; Thorhauge, J.; Hazell, R. G.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2001, 40, 160.
18.Halland, N.; Hansen, T.; Jøgensen, K. A. Angew. Chem. Int. Ed. 2003, 42, 4955.
19.Movassaghi, M.; Jacobsen, E. N. Science 2002, 298, 1904.
20.Juhl, K.; Jørgensen, K.A. Angew. Chem. Int. Ed. 2003, 42, 1498.
21. Franzén, J.; Marigo, M.; Fielenbach, D.; Wabnitz, T. C.; Kjærsgaard, A.; Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 18296.
22.(a) Bakshi, R. K.; Shibata, S.; Corey, E. J. J. Am. Chem. Soc. 1987, 109, 5551.
(b) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem. Int. Ed. 2005, 44, 4212.
23.Marigo, M.; Schulte,T.; Franzén, J.; Jørgensen, K. A. J. Am. Chem. Soc., 2005, 127, 15710.
24.Enders, D.; Hüttl, M. R. M.; Grondal, C.; Raabe, G. Nature 2006, 441, 861.
25.(a) Rios, R.; Sundén, H.; Ibrahem, I.; Zhao, G.-L.; Eriksson, L.; Córdova, A. Tetrahedron Lett. 2006, 47, 8547;
(b) Sunden, H. ; Ibrahem, I.; Zhao, G.-L.; Eriksson, L.; Córdova, A. Chem. Eur. J. 2007, 13, 574.
(c) Zu, L.; Li, H.; Xie, H.; Wang, J.; Jiang, W.; Tang, Y.; Wang, W. Angew. Chem. Int. Ed. 2007, 46, 3732.
26.(a) Franke, P. T.; Richter, B.; Jørgensen, K. A. Chem. Eur. J. 2008, 14, 6317.
(b) Rueping, M.: Sugiono, E.; Merino, E. Chem.Eur. J. 2008, 14, 6329
27.Anwar, S.; Chang, H. J.; Chen, K. Org. Lett. 2011, 13, 2200.
28.Chen,J.-H.; Chang, C.; Chang, H.-J.; Chen, K. Org. Biomol. Chem. 2011, 9, 7510.
29.Wen,S.-S.; Wang, J.; Luo,Y.-M. ;Yang, H. Tetrahedron 2014, 70, 9314.
30.Han,J.; Wang, T.; Feng,S.; Li, C.; Zhang, Z. Green Chem. 2016, 18, 4092.
31.Nishinaga, A.; Ando, H.; Marayama, K.; Mashino, T. Synthesis 1992, 839.