臺灣博碩士論文加值系統

有機催化連鎖反應應用於官能基化螺環與雙環化合物之合成
本文包含三部份：第一章說明有機催化劑在不對稱合成反應的應用與發展，其中包含共價鍵－烯胺及亞胺離子催化反應、非共價鍵－相轉移催化劑、氫鍵催化劑及天然生物鹼作為催化劑，應用於不對稱催化反應，成功建立碳－碳鍵結之例子。
第二章描述三大主題：第一部分說明利用有機催化進行[5+1]環化反應，經由Michael-Aldol 連鎖反應合成六員螺環茚滿-1,3- 二酮/ 羥吲哚
（indane-1,3-diones/oxindoles）。此反應成功地以1,3-二酮/羥吲哚/香豆酮作為雙親核試劑（ dinucleophilic components ） 及(E)-5- 硝基-6- 芳基- 己-5- 烯-2- 酮
（(E)-5-nitro-6-aryl-hex-5-en-2-one）為雙親電子試劑（dielectrophile）於DBACO存在之鹼性條件下，有效得到雙螺環結構之產物，並擁有不錯的產率（30-84%）及非鏡像選擇性（>95 : 5 dr）表現。
第二部分主軸是透過掌性方醯胺（squaramide）催化劑，進行Michael/Aldol 反應，獲得連續三個立體中心之螺環己烷二茚-1,3- 二酮（spirocyclohexaneindan-1,3-diones）衍生物，其中非鏡像及鏡像選擇性均表現優異。
第三部分：透過3-甲基-1-芳基-2-吡唑啉-5-酮（3-methyl-1-aryl-2-pyrazolin-5-ones）與(E)-5-硝基-6-芳基-己-5-烯-2-酮（(E)-5-nitro-6-aryl-hex-5-en-2-ones）為起始物，
加入方醯胺催化劑進行不對Michael/Aldol 連鎖反應，建構了連續四個立體中心之螺吡喃酮（spiropyrazolone）衍生物，並控制其立體選擇性（up to >20: 1 dr, 94%ee）。
第三章描述如何透過溫和的反應條件，發展出鹼催化sulfa-Michael/Aldol 反應合成雙環四氫噻吩（biheterocyclic tetrahydrothiophene）衍生物之方法，並兼具官能基忍受度廣及起始物容易製備等優點，提供一個快速且有效率的雙環化合物合成途徑。

The content of this thesis is divided into three chapters. The chapter-I, illustrate overview on asymmetric synthesis and organocatalysis. It includes, terminology, introduction to asymmetric synthesis, some historical aspects of organocatalysts, classification and utilization of covalent
catalysis including iminium and enamine, non-covalent catalysis including phase-transfer catalysts, hydrogen bonding catalysts and importance of alkaloids in asymmetric synthesis as organocatalysts. And successful applications on important C-C bond forming asymmetric Michael domino/cascade/tandem reactions are presented. The interesting art of hydrogen bonding, namely, the formation of double hydrogen bonds between organic molecules is also described.
II.1. Organocatalytic formal [5+1] annulation: diastereoselective cascade synthesis of functionalized six-membered spirocyclic indane-1,3-diones/oxindoles via Michael-aldol reaction
Chapter-II is divided into 3 sections. Section-1, represents the diastereoselective synthesis of functionalized six membered spirocyclic compounds via Michael-aldol cascade reaction. The reaction proceeds smoothly between indane 1,3-diones/oxindoles/coumaranone as the dinucleophilic components and (E)-5-nitro-6-aryl-hex-5-en-2-one as the dielectrophile in presence of DABCO to give the desired spirocyclic products with reasonable to high chemical yields (30- 84%) and high levels of diastereoselectivities (up to >95:5 dr).

II.2. Organocatalytic synthesis of spirocyclohexane indan-1, 3-diones via a chiral squaramide-catalyzed Michael/aldol cascade reaction of γ-nitro ketones and 2- arylideneindane-1, 3-diones.
This section describes a chiral squaramide catalyzed stereoselective synthesis of spirocyclohexane indan-1, 3-diones via Michael-aldol cascade reaction of 2-arylideneindan-1, 3-diones and γ- nitroketones. The reaction produces three stereogenic centers having spirocyclohexaneindan-1, 3- diones derivatives with excellent diastereo and high enantioselectivity in good to excellent yields.

II.3. Organocatalytic one-pot asymmetric synthesis of functionalized spiropyrazolones via a Michaelaldol sequential reaction.
In this section an efficient organocatalytic stereoselective method for the synthesis of functionalized spiropyrazolone derivatives with four contiguous stereogenic centers has been developed through a chiral squaramide catalyzed Michael-aldol sequential reaction. The reaction between 3-methyl-1-aryl-2-pyrazolin-5-ones and (E)-5-nitro-6-aryl-hex-5-en-2-ones is catalyzed by a quinine derived squaramide to give the desired spiropyrazolone derivatives in moderate-to-good
yields (up to 80%) with good-to-excellent stereoselectivities (up to >20: 1 dr, 94% ee).

III. Organocatalytic diastereoselective [3+2] annulation of 1, 4-dithiane-2, 5-diol and nitro allylic amines via sulfa-Michael-aldol cascade reaction.
The chapter III, discloses base catalyzed cascade sulfa-Michael-aldol reaction for the synthesis of novel class of biheterocyclic tetrahydrothiophene derivatives in good yield with high diastereoselectivity. The mild reaction conditions, good functional group tolerance, and broad
range of nitro allylic compounds are salient features of this protocol. Due to the easy preparation of the starting materials, we believe this methodology provides a simplified route for the synthesis of biheterocyclic thiophene derivatives.

Chapter-I
I. Overview on Asymmetric synthesis and Organocatalysis
I.1 Terminology in asymmetric synthesis 1
I.2. Introduction to asymmetric synthesis 4
I.3. Historical background of asymmetric organocatalysis 6
I.4. Covalent bonding catalysis 7
I.5. Amino catalysis: proline derivatives 9
I.6. Organocatalytic domino reactions 10
1.7. N-heterocyclic carbenes 12
I.8. Non-covalent bonding catalysis 13
I.9. Bifunctional amine-squaramide catalysis 16
I.10. Alkaloids as organocatalysts 19
I.11. Chiral ion-pair catalysis 21
I.12. References 23
CHAPTER-II
II.1. Organocatalytic formal [5+1] annulation: diastereoselective cascade synthesis of functionalized six-membered spirocyclic indane-1,3-diones/oxindoles via Michael-aldol reaction
II.1.1. Introduction 29
II.1.2. Review of literature 29
II.1.3. Results and discussions 32
II.1.4. Conclusions 46
II.1.5. Experimental section 46
II.1.6. References 57
II.2. Organocatalytic synthesis of spirocyclohexane indane-1, 3-diones via a chiral squaramide-catalyzed Michael/aldol cascade reaction of γ-nitro ketones and 2-arylideneindane-1, 3-diones
II.2.1. Introduction 60
II.2.2. Review of literature 61
II.2.3. Results and discussions 62
II.2.4. Conclusions 68
II.2.5. Experimental section 68
II.2.6. References 84
II.3. Organocatalytic one-pot asymmetric synthesis of functionalized spiropyrazolones via a Michael-aldol sequential Reaction
II.3.1. Introduction 88
II.3.2. Review of literature 89
II.3.3. Results and discussions 90
II.3.4. Conclusions 97
II.3.5. Experimental Section 98
II.3.6. References 115
CHAPTER-III
III.1Organocatalytic diastereoselective [3+2] annulation of 1, 4-dithiane 2, 5-diol and nitro allylic amines via sulfa-Michael-aldol cascade reaction
III.1.1. Introduction 119
III.1.2. Review of literature 120
III.1.3. Results and discussions 122
III.1.4. Conclusions 129
III.1.5. Experimental Section 129
III.1.6. References 135
X-ray crystallographic data 137
1H and 13C NMR spectral copies 240
List of publications 311

I.12. References
1. (a) Berkessel, A.; Gröger, H. Asymmetric organocatalysis: from biomimetic concepts to
applications in asymmetric synthesis; John Wiley & Sons, 2006. (b) Enantioselective
Organocatalysis: Reactions and Experimental Procedures, (Eds.: Dalko, P.I. Wiley-VCH,
Verlag, 2007.
2. Yamamoto, H.; Carreira, E. M. Comprehensive chirality; New York: Elsevier Science,
2012.
3. Dyer, A.; Reference Module in Chemistry, Molecular Sciences and Chemical Engineering
Elsevier: 2013.
4. Lin, G.-Q.; Zhang, J.-G.; Cheng, J.-F. In Chiral Drugs; John Wiley & Sons, Inc.: 2011, p
3-28.
5. Chhabra, N.; Aseri, M. L.; Padmanabhan, D. International Journal of Applied and Basic
Medical Research 2013, 3, 16.
6. Reetz, M.T.; List, B.; Jaroch, S.; Weinmann, H.; Organocatalysis.
7. For metal catalysis: a) Noyori, R. Asymmetric catalysis in organic synthesis, 1994; b) Jacobsen, E.; Wu, M.; Springer-Verlag, Berlin-Heidleberg-New York: 1999.
8. For Biocatalysis: a) Drauz, K. Enzyme catalysis in organic synthesis: a comprehensive handbook; John Wiley & Sons, 2012; b) Bommarius, A. S.; Riebel-Bommarius, B. R. Biocatalysis: fundamentals and applications; John Wiley & Sons, 2004.
9. Topics in current chemistry: Asymmetric Organocatalysis, Eds.: List, B. Springer, Verlag, 291, 2010.
10. List, B.; Lerner, R. A.; Barbas, C. F. J. Am. Chem. Soc. 2000, 122, 2395-2396.
11. Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243-4244.
12. Moyano, A. In Stereoselective Organocatalysis; John Wiley & Sons, Inc.: 2013, p 11-80.
13. Waser, M. Asymmetric organocatalysis in natural product syntheses; Springer Science & Business Media, 2012; Vol. 96.
14. Gaunt, M. J.; Johansson, C. C. C.; McNally, A.; Vo, N. T. Drug Discovery Today 2007, 12, 8-27.
15. (a) Masson, G.; Housseman, C.; Zhu, J. Angew. Chem. Int. Ed. 2007, 46, 4614-4628. (b) Aroyan, C. E.; Dermenci, A.; Miller, S. J. Tetrahedron 2009, 65, 4069-4084. (c) Mansilla,
J.; Saá, J. M. Molecules 2010, 15, 709-734. (d) Wei, Y.; Shi, M. Acc. Chem. Res. 2010, 43, 1005-1018.
16. Wohler, F.; Liebig, J. J. Ann. Pharm 1832, 3, 249-282.
17. Von Liebig, J. Justus Liebigs Ann. Chem. 1860, 113, 246-247.
18. Knoevenagel, E. Ber. Dtsch. Chem. Ges. 1896, 29, 172-174.
19. Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1615-1621.
20. Eder, U.; Sauer, G.; Wiechert, R. Angew. Chem. Int. Ed. 1971, 10, 496-497.
21. Danishefsky, S. J.; Masters, J. J.; Young, W. B.; Link, J.; Snyder, L. B.; Magee, T. V.; Jung, D. K.; Isaacs, R. C.; Bornmann, W. G.; Alaimo, C. A. J. Am. Chem. Soc. 1996, 118, 2843-2859.
22. Rychnovsky, S. D.; Mickus, D. E. J. Org. Chem. 1992, 57, 2732-2736.
23. Tietze, L. F.; Beifuss, U. Angew. Chem. Int. Ed. 1993, 32, 131-163.
24. Fogg, D. E.; dos Santos, E. N. Coord. Chem. Rev. 2004, 248, 2365-2379.
25. (a) Enders, D.; Grondal, C.; Hüttl, M. R. M. Angew. Chem. Int. Ed. 2007, 46, 1570-1581.(b) Enders, D.; Narine, A. A. J. Org. Chem. 2008, 73, 7857-7870. (c) Pellissier, H. Adv. Synth. Catal. 2012, 354, 237-294. (d) Grondal, C.; Jeanty, M.; Enders, D. Nat. Chem. 2010, 2, 167-178.
26. Bertelsen, S.; Jørgensen, K. A. Chem. Soc. Rev. 2009, 38, 2178-2189.
27. (a) Halland, N.; Aburel, P. S.; Jørgensen, K. A. Angew. Chem. 2004, 116, 1292-1297. (b) Reyes, E.; Jiang, H.; Milelli, A.; Elsner, P.; Hazell, R. G.; Jørgensen, K. A. Angew. Chem. 2007, 119, 9362-9365.
28. Enders, D.; H. Reyes, E.; Jiang, H.; Milelli, A.; Nature 2006, 441, 861-863.
29. Sheehan, J. C.; Hunneman, D. H. J. Am. Chem. Soc. 1966, 88, 3666-3667.
30. Flanigan, D.M.; Romanov-Michailidis, F.; White, N.A; Rovis, T. Chem. Rev. 2015, 115, 9307−9387.
31. (a) Akiyama, T. Chem. Rev. 2007, 107, 5744-5758. (b) Rueping, M.; Nachtsheim, B. J.; Ieawsuwan, W.; Atodiresei, I. Angew. Chem. Int. Ed. 2011, 50, 6706-6720.
32. (a) Schreiner, P. R. Chem. Soc. Rev. 2003, 32, 289-296. (b) Connon, S. J. Chem. Eur. J. 2006, 12, 5418-5427. (c) Taylor, M. S.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520-1543. (d) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713-5743. (e) Zhang, Z.; Schreiner, P. R. Chem. Soc. Rev. 2009, 38, 1187-1198.
33. (a) Malerich, J. P.; Hagihara, K.; Rawal, V. H. J. Am. Chem. Soc. 2008, 130, 14416-14417. (b) Alem416-14417.oc.Hagihara, K.; Rawal, V. H. Chem. Eur. J. 2011, 17, 6890-6899.
34. Knowles, R. R.; Jacobsen, E. N. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 20678-20685.
35. Pihko, P. M. Hydrogen bonding in organic synthesis; John Wiley & Sons, 2009.
36. Coiro, V.; Giacomello, P. t.; Giglio, E. Acta Cryst. 1971, 27, 2112-2119.
37. (a) Hine, J.; Linden, S. M.; Kanagasabapathy, V. J. Am. Chem. Soc. 1985, 107, 1082-1083. (b) Hine, J.; Linden, S. M.; Kanagasabapathy, V. M. J. Org. Chem. 1985, 50, 5096-5099. (c) Hine, J.; Ahn, K.; Gallucci, J.; Linden, S.-M. Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 1990, 46, 2136-2146.
38. (a) Curran, D. P.; Kuo, L. H. J. Org. Chem. 1994, 59, 3259-3261. (b) Curran, D. P.; Kuo, L. H. Tetrahedron Lett. 1995, 36, 6647-6650.
39. Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 4901-4902.
40. (a) Vachal, P.; Jacobsen, E. N. Org. Lett. 2000, 2, 867-870. (b) Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2000, 39, 1279-1281.
41. Berkessel, A.; Cleemann, F.; Mukherjee, S.; Müller, T. N.; Lex, J. Angew. Chem. Int. Ed. 2005, 44, 807-811.
42. Vakulya, B.; Varga, S.; Csámpai, A.; Soós, T. Org. Lett. 2005, 7, 1967-1969.
43. McCooey, S. H.; Connon, S. J. Angew. Chem. 2005, 117, 6525-6528.
44. (a) Tomàs, S.; Prohens, R.; Vega, M.; Rotger, M. C.; Deyà, P. M.; Ballester, P.; Costa, A. J. Org. Chem. 1996, 61, 9394-9401. (b) Ramalingam, V.; Domaradzki, M. E.; Jang, S.; Muthyala, R. S. Org. Lett. 2008, 10, 3315-3318.
45. Merritt, J. R.; Rokosz, L. L.; Nelson, K. H.; Kaiser, B.; Wang, W.; Stauffer, T. M.; Ozgur, L. E.; Schilling, A.; Li, G.; Baldwin, J. J. Bioorg. Med. Chem. Lett. 2006, 16, 4107-4110.
46. Konishi, H.; Lam, T. Y.; Malerich, J. P.; Rawal, V. H. Org. Lett. 2010, 12, 2028-2031.
47. Qian, Y.; Ma, G.; Lv, A.; Zhu, H.-L.; Zhao, J.; Rawal, V. H. Chem. Commun. 2010, 46, 3004-3006.
48. Albrecht, Ł.; Dickmeiss, G.; Acosta, F. C.; Rodríguez-Escrich, C.; Davis, R. L.; Jørgensen, K. A. J. Am. Chem. Soc. 2012, 134, 2543-2546.
49. Zhu, Y.; Li, X.; Chen, Q.; Su, J.; Jia, F.; Qiu, S.; Ma, M.; Sun, Q.; Yan, W.; Wang, K.; Wang, R. Org. Lett. 2015, 17, 3826-3829.
50. (a) Yang, W.; Yang, Y.; Du, D.-M. Org. Lett. 2013, 15, 1190-1193. (b) Li, J.-H.; Du, D.-M. Org. Biomol. Chem. 2015, 13, 5636-5645. (c) Zhao, B.-L.; Lin, Y.; Yan, H.-H.; Du, D.-M. Org. Biomol. Chem. 2015, 13, 11351-11361.
51. Bredig, G.; Fiske, P. Biochem. Zeits 1912, 46, 7-23.
52. (a) Pracejus, H. Justus Liebigs Ann. Chem. 1960, 634, 9-22. (b) Pracejus, H. Justus Liebigs Ann. Chem. 1960, 634, 23-29. (c) Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719-724.
53. Starks, C. M. J. Am. Chem. Soc. 1971, 93, 195-199.
54. Ooi, T.; Maruoka, K. Angew. Chem. Int. Ed. 2007, 46, 4222-4266.
55. Dehmlow, Eckehard V.; Düttmann, S.; Neumann, B.; Stammler, H.-G. Eur. J. Org. Chem. 2002, 2087-2093.
56. Mahlau, M.; List, B. Angew. Chem. Int. Ed. 2013, 52, 518-533.
57. Phipps, R. J.; Hamilton, G. L.; Toste, F. D. Nat. Chem. 2012, 4, 603-614.
58. (a) Ooi, T.; Maruoka, K. Angew. Chem. Int. Ed. 2007, 46, 4222-4266. (b) Shirakawa, S.; Maruoka, K. Angew. Chem. Int. Ed. 2013, 52, 4312-4348.
59. (a) Ganesh, M.; Seidel, D. J. Am. Chem. Soc. 2008, 130, 16464-16465. (b) Uyeda, C.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 9228-9229.
60. Govender, T.; Arvidsson, P. I.; Maguire, G. E. M.; Kruger, H. G.; Naicker, T. Chem. Rev. 2016, 116, 9375-9437.

II.1.6. References
1.(a) Tietze, L. F.; Beifuss, U. Angew. Chem. 1993, 105, 137-170. Angew. Chem. Int. Ed. Engl. 1993, 32, 131-163. (b) Tietze, L. F. Chem. Rev. 1996, 96, 115-136.(c) Denmark, S. E.; Thorarensen, A. Chem. Rev. 1996, 96, 137-165. (d) Fogg, D. E.; dos Santos, E. N. Coord. Chem. Rev. 2004, 248, 2365-2379. (e) Tietze, L. F.; Brasche, G.; Gericke, K. Domino Reactionsin Organic Synthesis; Wiley-VCH: Weinheim; (f)Chapman, C. J.; Frost, C. G. Synthesis 2007, 1-21.(g) Enders, D.; Grondal, C.; Hüttl, M. R. M. Angew. Chem. Int. Ed. 2007, 46, 1570-1581.(h) Yu, X.; Wang, W. Org. Biomol. Chem. 2008, 6, 2037-2046. (i)Pellissier, H. Adv. Synth. Catal. 2012, 354, 237-294. (j) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem. Int. Ed. 2006, 45, 7134-7186.
2. (a) Hulme, C.; Gore, V. Curr. Med. Chem. 2003, 10, 51-80. (b) Colombo, M.; Peretto, I. Drug Discov. Today 2008, 13, 677-684. (c) Touré, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439-4486. (d) Nicolaou, K. C.; Chen, J. S. Chem. Soc. Rev. 2009, 38, 2993-300. (e) Grondal, C.; Jeanty, M.; Enders, D. Nat. Chem. 2010, 2, 167-178.
3. (a) Venkatesan, H.; Davis, M. C.;Altas, Y.; Snyder, J. P.; Liotta, D. C. J. Org. Chem. 2001, 66, 3653-3661. (b) Lin, H.; Danishefsky, S. J. Angew. Chem. Int. Ed. 2003, 42, 36-51. (c) Fensome, A.; Koko, M.; Wrobel, J.; Zhang, P.; Zhang, Z.; Cohen, J.; Lundeen, S.; Rudnick, K.; Zhu, Y.; Winneker, R. Bioorg. Med. Chem. Lett. 2003, 13, 1317-1320. (d) Zhou, X.; Xiao, T.; Iwama, Y.; Qin, Y. Angew. Chem. Int. Ed. 2012, 51, 4909-4912.
4.(a) Lan, Y.-B.; Zhao, H.; Liu, Z.-M.; Liu, G.-G.; Tao, J.-C.; Wang, X.-W. Org. Lett. 2011, 13, 4866-4869. (b) Shen, L.-T.; Jia, W.-Q.; Ye, S. Angew. Chem. Int. Ed. 2013, 52, 585-588. (c) Wang, L.-L.; Peng, L.; Bai, J.-F.; Huang, Q.-C.; Xu, X.-Y.; Wang, L.-X. Chem. Commun. 2010, 46, 8064-8066. (d) Bencivenni, G.; Wu, L.-Y.; Mazzanti, A.; Giannichi, B.; Pesciaioli, F.; Song, M.-P.; Bartoli, G.; Melchiorre, P. Angew. Chem. Int. Ed. 2009, 48, 7200-7203.
5. Zhou, B.; Yang, Y.; Shi, J.; Luo, Z.; Li, Y. J. Org. Chem. 2013, 78, 2897-2907.
6. Jiang, K.; Jia, Z.-J.; Chen, S.; Wu, L.; Chen, Y.-C. Chem. Eur. J.. 2010, 16, 2852-2856.
7. Wu, B.; Chen, J.; Li, M.-Q.; Zhang, J.-X.; Xu, X.-P.; Ji, S.-J.; Wang, X.-W. Eur. J. Org. Chem. 2012, 2012, 1318-1327.
8. Clive, D. L. J.; Kong, X.; Paul, C. C. Tetrahedron 1996, 52, 6085-6116.
9. Pizzirani, D.; Roberti, M.; Grimaudo, S.; Di Cristina, A.; Pipitone, R. M.; Tolomeo, M.; Recanatini, M. J. Med. Chem. 2009, 52, 6936-6940.
10. (a) Boger, D. L.; Jacobson, I. C. J. Org. Chem. 1990, 55, 1919-1928. (b) Wilson, K. E.; Tsou, N. N.; Guan, Z.; Ruby, C. L.; Pelaez, F.; Gorrochategui, J.; Vicente, F.; Onishi, H. R. Tetrahedron Lett. 2000, 41, 8705-8709. (c) Nicolaou, K. C.; Montagnon, T.; Vassilikogiannakis, G.; Mathison, C. J. N. J. Am. Chem. Soc. 2005, 127, 8872-8888.
11. (a) Kuck, D.; Schuster, A.; Krause, R. A. J. Org. Chem. 1991, 56, 3472-3475. (b) Schuster, A.; Kuck, D. Angew. Chem. Int. Ed.1991, 30, 1699-1702. (c) Bredenkotter, B.; Barth, D.; Kuck, D.; Kuck, D. Chem. Commun. 1999, 847-848.(d) Bredenkötter, B.; Flörke, U.; Kuck, D. Chem.--Eur. J. 2001, 7, 3387-3400. (e) Tellenbröker, J.; Kuck, D. Eur. J. Org. Chem. 2001, 2001, 1483-1489
12. (a) Ramachary, D.; Chowdari, N. S.; BARBAS, C. F. Synlett 2003, 1910-1914. (b) Ramachary, D. B.; Anebouselvy, K.; Chowdari, N. S.; Barbas, C. F. J. Org. Chem. 2004, 69, 5838-5849. (c) Ramachary, D. B.; Barbas, C. F. Chem. Eur. J. 2004, 10, 5323-5331. (d) Pizzirani, D.; Roberti, M.; Recanatini, M. Tetrahedron Lett. 2007, 48, 7120-7124. (e) Ramachary, D. B.; Venkaiah, C.; Murali Krishna, P. Chem. Commun. 2012, 48, 2252-2254. (f) Dai, B.; Song, L.; Wang, P.; Yi, H.; Cao, W.; Jin, G.; Zhu, S.; Shao, M. Synlett 2009, 1842-1846.

13. For selected references on cascade Michael-aldol sequence: (a) Bui, T.; Barbas, C. F. Tetrahedron Lett. 2000, 41, 6951-6954. (b) Wang, J.; Li, H.; Xie, H.; Zu, L.; Shen, X.; Wang, W. Angew. Chem. 2007, 119, 9208-9211. (c) Rueping, M.; Kuenkel, A.; Tato, F.; Bats, J. W. Angew. Chem. 2009, 121, 3754-3757. (d) Reyes, E.; Talavera, G.; Vicario, J. L.; Badía, D.; Carrillo, L. Angew. Chem. 2009, 121, 5811-5814. (e) Luo, S.-P.; Li, Z.-B.; Wang, L.-P.; Guo, Y.; Xia, A.-B.; Xu, D.-Q. Org. Biomol. Chem. 2009, 7, 4539-4546. (f) Hong, B.-C.; Dange, N. S.; Hsu, C.-S.; Liao, J.-H. Org. Lett. 2010, 12, 4812-4815. (g) Cui, B.-D.; You, Y.; Zhao, J.-Q.; Zuo, J.; Wu, Z.-J.; Xu, X.-Y.; Zhang, X.-M.; Yuan, W.-C. Chem. Commun. 2015, 51, 757-760. (h) Liu, C.; Zhang, X.; Wang, R.; Wang, W. Org. Lett. 2010, 12, 4948-4951. (i) Tang, J.; Xu, D. Q.; Xia, A. B.; Wang, Y. F.; Jiang, J. R.; Luo, S. P.; Xu, Z. Y. Adv. Synth. Catal. 2010, 352, 2121-2126. (j) Gao, Y.; Ren, Q.; Wu, H.; Li, M.; Wang, J. Chem. Commun. 2010, 46, 9232-9234 (k) Tan, B.; Candeias, N. R.; Barbas III, C. F. Nat. Chem. 2011, 3, 473-477.
14. (E)-6-(Aryl/alkyl)-5-nitrohex-5-en-2-one (1a-o) were prepared following the literature procedure, see: (a) Dadwal, M.; Mohan, R.; Panda, D.; Mobin, S. M.; Namboothiri, I. N. N. Chem. Commun. 2006, 338-340. (b) Shanbhag, P.; Nareddy, P. R.; Dadwal, M.; Mobin, S. M.; Namboothiri, I. N. N. Org. Biomol. Chem. 2010, 8, 4867-4873.
15. Detailed X-ray crystallographic data for compounds 2a (CCDC 930107) and 3a (CCDC 930108) can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
II.2.6.References
1.(a) Ghosh, A. K.; Zhou, B. Tetrahedron Lett. 2013, 54, 2311-2314; (b) Fensome, A.; Adams, W.
R.; Adams, A. L.; Berrodin, T. J.; Cohen, J.; Huselton, C.; Illenberger, A.; Kern, J. C.; Hudak, V.
A.; Marella, M. A.; Melenski, E. G.; McComas, C. C.; Mugford, C. A.; Slayden, O. D.; Yudt, M.;
Zhang, Z.; Zhang, P.; Zhu, Y.; Winneker, R. C.; Wrobel, J. E. J. Med. Chem. 2008, 51, 1861-1873;
(c) Beccalli, E. M.; Clerici, F.; Gelmi, M. L. Tetrahedron 2003, 59, 4615-4622; (d) Venkatesan,
H.; Davis, M. C.; Altas, Y.; Snyder, J. P.; Liotta, D. C. J. Org. Chem. 2001, 66, 3653-3661; (e)
Schultz, A. G. Acc. Chem. Res. 1990, 23, 207-213.
2.(a) Ramachary, D. B.; Venkaiah, C.; Murali Krishna, P. Chem. Commun. 2012, 48, 2252-2254;
(b) Pizzirani, D.; Roberti, M.; Grimaudo, S.; Di Cristina, A.; Pipitone, R. M.; Tolomeo, M.
Recanatini, M. J. Med. Chem. 2009, 52, 6936-6940; (c) Nicolaou, K. C.; Montagnon, T.;
Vassilikogiannakis, G.; Mathison, C. J. N. J. Am. Chem. Soc. 2005, 127, 8872-8888; (d) Nicolaou,
K. C.; Montagnon, T.; Vassilikogiannakis, G. Chem. Commun. 2002, 2478-2479; (e) Wilson, K.
E.; Tsou, N. N.; Guan, Z.; Ruby, C. L.; Pelaez, F.; Gorrochategui, J.; Vicente, F.; Onishi, H. R.
Tetrahedron Lett. 2000, 41, 8705-8709; (f) Bredenkotter, B.; Barth, D.; Kuck, D.; Kuck, D. Chem.
Commun. 1999, 847-848; (g) Russell, G. A.; Wang, K. J. Org. Chem. 1991, 56, 3475-3479; (h)
Schuster, A.; Kuck, D. Angew. Chem. Int. Ed. 1991, 30, 1699-1702.
3.(a) Yoakim, C.; Ogilvie, W. W.; Goudreau, N.; Naud, J.; Haché, B.; O'Meara, J. A.; Cordingley,
M. G.; Archambault, J.; White, P. W. Bioorg. Med. Chem. Lett. 2003, 13, 2539-2541; (b) Clive,
D. L. J.; Kong, X.; Paul, C. C. Tetrahedron 1996, 52, 6085-6116.
4. (a) Bredenkötter, B.; Flörke, U.; Kuck, D. Chem. Eur. J. 2001, 7, 3387-3400; (b) Tellenbröker,
J.; Kuck, D. Eur. J. Org. Chem. 2001, 1483-1489.
5.(a) Dai, B.; Song, L.; Wang, P.; Yi, H.; Cao, W.; Jin, G.; Zhu, S.; Shao, M. Synlett 2009, 2009,
1842-1846; (b) Pizzirani, D.; Roberti, M.; Recanatini, M. Tetrahedron Lett. 2007, 48, 7120-7124;
(c) Ramachary, D. B.; Barbas, C. F. Chem. Eur. J. 2004, 10, 5323-5331; (d) Ramachary, D. B.;
Anebouselvy, K.; Chowdari, N. S.; Barbas, C. F. J. Org. Chem. 2004, 69, 5838-5849; (e)
Ramachary, D. B.; Chowdari, N. S.; Barbas Iii, C. F. Synlett 2003, 2003, 1910-1914.
6. (a) Li, X.; Yang, L.; Peng, C.; Xie, X.; Leng, H.-J.; Wang, B.; Tang, Z.-W.; He, G.; Ouyang,
L.; Huang, W.; Han, B. Chem. Commun. 2013, 49, 8692-8694; (b) Ball-Jones, N. R.; Badillo, J.
J.; Franz, A. K. Org. Biomol. Chem. 2012, 10, 5165-5181; (c) Pellissier, H. Adv. Synth. Catal.
2012, 354, 237-294; (d) Hu, F.; Wei, Y.; Shi, M. Tetrahedron 2012, 68, 7911-7919; (e) Singh, G.
S.; Desta, Z. Y. Chem. Rev. 2012, 112, 6104-6155; (f) Yu, X.; Wang, W. Org. Biomol. Chem.
2008, 6, 2037-2046.
7. (a) Anwar, S.; Li, S. M.; Chen, K. Org. Lett. 2014, 16, 2993-2995. (b) Roy, S.; Amireddy, M.;
Chen, K. Tetrahedron 2013, 69, 8751-8757; (c) Kuan, H.-H.; Chien, C.-H.; Chen, K. Org. Lett.
2013, 15, 2880-2883.
8. Han, B.; Huang, W.; Ren, W.; He, G.; Wang, J.-h.; Peng, C. Adv. Synth. Catal. 2015, 357, 561-
568.
9. (a) He, H.-X.; Yang, W.; Du, D.-M. Adv. Synth. Catal. 2013, 355, 1137-1148; (b) Yang, W.;
Yang, Y.; Du, D.-M. Org. Lett. 2013, 15, 1190-1193; (c) Yang, W.; Du, D.-M. Chem. Commun.
2013, 49, 8842-8844; (d) Yang, W.; He, H.-X.; Gao, Y.; Du, D.-M. Adv. Synth. Catal. 2013, 355,
3670-3678; (e) Yang, W.; Du, D.-M. Adv. Synth. Catal. 2011, 353, 1241-1246; (f) Yang, W.; Du,
D.-M. Chem. Commun. 2011, 47, 12706-12708; (g) Qian, Y.; Ma, G.; Lv, A.; Zhu, H.-L.; Zhao,
J.; Rawal, V. H. Chem. Commun. 2010, 46, 3004-3006; (h) Yang, W.; Du, D.-M. Org. Lett. 2010,
12, 5450-5453; (i) Xu, D.-Q.; Wang, Y.-F.; Zhang, W.; Luo, S.-P.; Zhong, A.-G.; Xia, A.-B.; Xu,
Z.-Y. Chem. Eur. J. 2010, 16, 4177-4180; (j) Konishi, H.; Lam, T. Y.; Malerich, J. P.; Rawal, V.
H. Org. Lett. 2010, 12, 2028-2031; (k) Dai, L.; Wang, S.-X.; Chen, F.-E. Adv. Synth. Catal. 2010,
352, 2137-2141.
10. Detailed X-ray crystallographic data for compounds 3ga (CCDC 1056328) can be obtained
free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
11. During manuscript preparation similar Michael-aldol reaction between arylidine 1,3-indanediones and nitro aldehydes was reported. Duan, J.; Cheng, J.; Li, P. Org. Chem. Front. 2015, 2, 1048-1052.
12. (a) Giorgi, G.; López-Alvarado, P.; Miranda, S.; Rodriguez, J.; Menéndez, J. C. Eur. J. Org. Chem. 2013, 1327-1336; (b) O’Connell, K. M. G.; Díaz-Gavilán, M.; Galloway, W. R. J. D.; Spring, D. R. Beilstein J. Org. Chem. 2012, 8, 850-860.

II.3.6. References
1. Varvounis, G. In Adv. Heterocycl. Chem.; Alan, R. K., Ed.; Academic Press: 2009; Vol. 98, p
143-224.
2. Li, Y.; Zhang, S.; Yang, J.; Jiang, S.; Li, Q. Dyes and Pigments 2008, 76, 508-514.
3. (a) Brogden, R. N. Drugs 1986, 32, 60-70; b) Yoshida, H.; Yanai, H.; Namiki, Y.; Fukatsu‐
Sasaki, K.; Furutani, N.; Tada, N. CNS Drug Rev. 2006, 12, 9-20; c) Chande, M. S.; Barve, P. A.;
Suryanarayan, V. J. Heterocycl. Chem. 2007, 44, 49-53; d) Bondock, S.; Rabie, R.; Etman, H. A.;
Fadda, A. A. Eur. J. Org. Chem. 2008, 43, 2122-2129.
4. (a) Schlemminger, I. P. Hummel, A. Hatzelmann, C. Zitt, A. Wohlsen, D. Marx, H.-P. Kley, D.
Ockert, A. Heuser, JAM Christiaans, GJ Sterk, WMPB Menge(Nycomed GmbH, Germany), WO2008138939 2010; (b) Hadi, V.; Koh, Y.-H.; Sanchez, T. W.; Barrios, D.; Neamati, N.; Jung, K. W. Bioorg. Med. Chem. Lett. 2010, 20, 6854-6857.
5. (a) Trost, B. M.; Brennan, M. K. Synthesis 2009, 3003-3025; b) Rios, R. Chem. Soc. Rev. 2012, 41, 1060-1074; (c) Nakazaki, A.; Kobayashi, S. Synlett 2012, 1427-1445; (d) Franz, A. K.; Hanhan, N. V.; Ball-Jones, N. R. ACS Catal. 2013, 3, 540-553; (e) Smith, L. K.; Baxendale, I. R. Org. Biomol. Chem., 2015, 13, 9907-9933; (f) Chauhan, P.; Mahajan, S.; Enders, D. Chem. Commun. 2015, 51, 12890-12907.
6. (a) Bencivenni, G.; Wu, L.-Y.; Mazzanti, A.; Giannichi, B.; Pesciaioli, F.; Song, M.-P.; Bartoli, G.; Melchiorre, P. Angew. Chem. Int. Ed. 2009, 48, 7200-7203; (b) Wei, Q.; Gong, L.-Z. Org. Lett. 2010, 12, 1008-1011; (c) Wang, L.-L.; Peng, L.; Bai, J.-F.; Huang, Q.-C.; Xu, X.-Y.; Wang, L.-X. Chem. Commun. 2010, 46, 8064-8066; (d) Lan, Y.-B.; Zhao, H.; Liu, Z.-M.; Liu, G.-G.; Tao, J.-C.; Wang, X.-W. Org. Lett. 2011, 13, 4866-4869; (e) Wang, L.-L.; Peng, L.; Bai, J.-F.; Jia, L.-N.; Luo, X.-Y.; Huang, Q.-C.; Xu, X.-Y.; Wang, L.-X. Chem. Commun. 2011, 47, 5593-5595.
7. (a) Roy, S.; Amireddy, M.; Chen, K. Tetrahedron 2013, 69, 8751-8757; (b) Anwar, S.; Li, S. M.; Chen, K. Org. Lett. 2014, 16, 2993-2995; (c) Amireddy, M.; Chen, K. Tetrahedron 2015, 71, 8003-8008.
8. (a) Kumar, V.; Kaur, K.; Gupta, G. K.; Sharma, A. K. Eur. J. Med. Chem., 2013, 69, 735-753; (b) McCormack, P. L. Drugs 2011, 71, 2457-2489.
9. (a) Zhou, F.; Liu, Y.-L.; Zhou, J. Adv. Synth. Catal. 2010, 352, 1381-1407; (b) Dalpozzo, R.; Bartoli, G.; Bencivenni, G. Chem. Soc. Rev. 2012, 41, 7247-7290; (c) Ball-Jones, N. R.; Badillo, J. J.; Franz, A. K. Org. Biomol. Chem., 2012, 10, 5165-5181.
10. (a) Hong, L.; Wang, R. Adv. Synth. Catal. 2013, 355, 1023-1052; (b) Liu, Y.; Wang, H.; Wan, J. Asian J. Org. Chem. 2013, 2, 374-386; (c) Chauhan, P.; Chimni, S. S. Tetrahedron: Asymmetry 2013, 24, 343-356; (d) Cheng, D.; Ishihara, Y.; Tan, B.; Barbas, C. F. ACS Catal. 2014, 4, 743-762; (e) Huang, H.; Bihani, M.; Zhao, J. C. G. Org. Biomol. Chem., 2016, 14, 1755-1763.
11. (a) Cui, B.-D.; Li, S.-W.; Zuo, J.; Wu, Z.-J.; Zhang, X.-M.; Yuan, W.-C. Tetrahedron 2014, 70, 1895-1902; (b) Zea, A.; Alba, A.-N. R.; Mazzanti, A.; Moyano, A.; Rios, R. Org. Biomol. Chem., 2011, 9, 6519-6523; (c) Chauhan, P.; Mahajan, S.; Loh, C. C. J.; Raabe, G.; Enders, D. Org. Lett. 2014, 16, 2954-2957; (d) Ceban, V.; Olomola, T. O.; Meazza, M.; Rios, R. Molecules 2015, 20, 8574-8582.
12. (a) Liang, J.; Chen, Q.; Liu, L.; Jiang, X.; Wang, R. Org. Biomol. Chem., 2013, 11, 1441-1445; (b) Zhang, J.-X.; Li, N.-K.; Liu, Z.-M.; Huang, X.-F.; Geng, Z.-C.; Wang, X.-W. Adv. Synth. Catal. 2013, 355, 797-808; (c) Liu, L.; Zhong, Y.; Zhang, P.; Jiang, X.; Wang, R. J. Org. Chem. 2012, 77, 10228-10234; (d) Chen, Q.; Liang, J.; Wang, S.; Wang, D.; Wang, R. Chem. Commun. 2013, 49, 1657-1659.
13. (a)Han, B.; Huang, W.; Ren, W.; He, G.; Wang, J.-h.; Peng, C. Adv. Synth. Catal. 2015, 357, 561-568; (b) Yang, W.; Zhang, Y.; Qiu, S.; Zhao, C.; Zhang, L.; Liu, H.; Zhou, L.; Xiao, Y.; Guo, H. RSC Advances 2015, 5, 62343-62347; (c) Li, J.-H.; Wen, H.; Liu, L.; Du, D.-M. Eur. J. Org. Chem. 2016, 2492-2499.
14. (a) Zheng, Y.; Cui, L.; Wang, Y.; Zhou, Z. J. Org. Chem. 2016, 81, 4340-4346; (b) Kumarswamyreddy, N.; Kesavan, V. Org. Lett. 2016, 18, 1354-1357; (c) Vila, C.; Amr, F. I.; Blay, G.; Muñoz, M. C.; Pedro, J. R. Chem. Asian J. 2016, 11, 1532-1536; (d) Li, J.-H.; Du, D.-M. Org. Biomol. Chem., 2015, 13, 5636-5645.
15. (a) Hack, D.; Dürr, A. B.; Deckers, K.; Chauhan, P.; Seling, N.; Rübenach, L.; Mertens, L.; Raabe, G.; Schoenebeck, F.; Enders, D. Angew. Chem. Int. Ed. 2016, 55, 1797-1800; (b) Han, X.; Yao, W.; Wang, T.; Tan, Y. R.; Yan, Z.; Kwiatkowski, J.; Lu, Y. Angew. Chem. Int. Ed. 2014, 53, 5643-5647. (c). J.-H. Li, Z.-H. Cui and D.-M. Du, Org. Chem. Front., 2016, 3, 1087-1090.
16. (a) Companyo, X.; Zea, A.; Alba, A.-N. R.; Mazzanti, A.; Moyano, A.; Rios, R. Chem. Commun. 2010, 46, 6953-6955; (b) Alba, A.-N. R.; Zea, A.; Valero, G.; Calbet, T.; Font-Bardía, M.; Mazzanti, A.; Moyano, A.; Rios, R. Eur. J. Org. Chem. 2011, 1318-1325; (c) Zhang, Y.; Wu, S.; Wang, S.; Fang, K.; Dong, G.; Liu, N.; Miao, Z.; Yao, J.; Li, J.; Zhang, W.; Sheng, C.; Wang, W. Eur. J. Org. Chem. 2015, 2030-2037.
17. Wu, B.; Chen, J.; Li, M.-Q.; Zhang, J.-X.; Xu, X.-P.; Ji, S.-J.; Wang, X.-W. Eur. J. Org. Chem. 2012, 1318-1327.
18. 3-Methyl-1-aryl-2-pyrazolin-5-ones were prepared using ref 12d.
19. (E)-5-nitro-6-aryl-hex-5-en-2-ones were prepared using: Dadwal, M.; Mohan, R.; Panda, D.; Mobin, S. M.; Namboothiri, I. N. N. Chem. Commun. 2006, 338-340.
20. Detailed X-ray crystallographic data for compounds 3a [CCDC 1492783] can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

III.6.References:
1. For recent reviews on Organocatalytic Carbon−Sulfur Bond-Forming Reactions (a) Chauhan, P.; Mahajan, S.; Enders, D. Chem. Rev. 2014, 114, 8807-8864. (b) Fernandez-Mejia, C. J. Nutr. Biochem. 2005, 16, 424. (c) Williams, D. R.; Jass, P. A.; Tse, H. L. A.; Gaston, R. D. J. Am. Chem. Soc. 1990, 112, 4552. (d) Gallienne, E.; Benazza, M.; Demailly, G.; Bolte, J.; Lemaire, M. Tetrahedron 2005, 61, 4557. (e) Begley, T. P. Nat. Prod. Rep. 2006, 23, 15. (f) Nudelman, A. 1984. The Chemistry of Optically Active Sulfur Compounds; Gordon and Breach: New York, 1984. (g) Damani, L. A. Sulphur containing drugs and related organic compounds: chemistry, biochemistry, and toxicology; Ellis Horwood, 1989; Vol. 3. (h) Clayden, J.; MacLellan, P. Beilstein J. Org. Chem. 2011, 7, 582-595.
2. (a) Benetti, S.; De Risi, C.; Pollini, G. P.; Zanirato, V. Chem. Rev. 2012, 112, 2129-2163. (b) Fernandez-Mejia, C. J. Nutr. Biochem. 2005, 16, 424-427. (c) Johnson, J. W.; Evanoff, D. P.; Savard, M. E.; Lange, G.;Ramadhar, T. R.; Assoud, A.; Taylor, N. J.; Dmitrienko, G. I. J. Org. Chem. 2008, 73, 6970.
3. (a) Ling, J.-B.; Su, Y.; Zhu, H.-L.; Wang, G.-Y.; Xu, P.-F. Org. Lett. 2012, 14, 1090-1093. (b) Su, Y.; Ling, J.-B.; Zhang, S.; Xu, P.-F. J. Org. Chem. 2013, 78, 11053-11058.
4. Shi, W.; Sun, S.; Hu, Y.; Gao, T.; Peng, Y.; Wu, M.; Guo, H.; Wang, J. Tetrahedron Lett. 2015, 56, 3861-3863.
5. (a) Vivek Kumar, S.; Prasanna, P.; Perumal, S. Tetrahedron Lett. 2013, 54, 6651-6655. (b) Bharkavi, C.; Kumar, S. V.; Perumal, S. Synlett 2015.
6. Liang, J.-J.; Pan, J.-Y.; Xu, D.-C.; Xie, J.-W. Tetrahedron Lett. 2014, 55, 6335-6338.
7. Zhou, P.; Cai, Y.; Lin, L.; Lian, X.; Xia, Y.; Liu, X.; Feng, X. Adv. Synth. Catal. 2015, 357, 695-700.
8. Zhong, Y.; Ma, S.; Li, B.; Jiang, X.; Wang, R. J. Org. Chem. 2015, 80, 6870-6874.
9. Hu, Y.-J.; Wang, X.-B.; Li, S.-Y.; Xie, S.-S.; Wang, K. D. G.; Kong, L.-Y. Tetrahedron Lett. 2015, 56, 105-108.
10. (a) Duan, S.-W.; Li, Y.; Liu, Y.-Y.; Zou, Y.-Q.; Shi, D.-Q.; Xiao, W.-J. Chem. Commun. 2012, 48, 5160-5162. (b) Zhao, B. L.; Liu, L.; Du, D. M. Eur. J. Org. Chem. 2014, 7850-7858.
11. Nitro allylic amines were prepared using literatre procedure. Gurubrahamam, R.; Chen, Y. m.; Huang, W.-Y.; Chan, Y.-T.; Chang, H.-K.; Tsai, M.-K.; Chen, K. Org. Lett. 2016, 18, 3046-3049.
12. Detailed X-ray crystallographic data for compounds 2a (CCDC 1453452) can be
obtained free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.