Synthesis of C2 Symmetric Organocatalysts and Investigation of Their Asymmetric Induction Effects in Aldol Reactions

Öz

Studies concerning optically active compounds occopy very important places both in industry and academic fields. Asymmetric catalysis is considered as an ideal method for synthesizing optically active compounds. Asymmetric induction in stereochemistry is described as the preferential formation of one enantiomer or diastereoisomer over the other in a chemical reaction as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment, which is a key element in asymmetric synthesis, first introduced by Emil Fischer based on his work on carbohydrates. The field received three Nobel Chemistry prizes for its importance. In this study, two L-proline–based organocatalysts were prepared through modified literature procedures. These compounds were identified by 1 H and 13C NMR and IR spectroscopy. Subsequently, their asymmetric induction in the aldol reaction between cyclohexanone and substituted benzaldehydes was evaluated. Both catalysts efficiently promoted the reactions, providing the respective aldol products with enantiomeric excesses of up to 94%.

Anahtar Kelimeler

• Cyclohexanone
• Aldol reaction
• Organocatalysis
• Proline
• Substituted aldehydes

Etik Beyan

Ethics committee approval was not required for this study because of there was no study on animals or humans.

Kaynakça

1. Almasi, D., Alonso, D. A., & Nájera, C. (2008). Water versus solvent-free conditions for the enantioselective inter- and intramolecular Aldol reaction employing L-prolinamides and L-prolinethioamides as organocatalysts. Advanced Synthesis & Catalysis, 350(14–15), 2467–2472. https://doi.org/10.1002/adsc.200800438
2. Bhatnagar, P. K., Heerding, D. A., Hartmann, M., Hiebl, J., & Kremminger, P. (1997). PCT International Application No. WO9717958 A1. World Intellectual Property Organization.
3. Dalko, P. I., & Moisan, L. (2004). In the golden age of organocatalysis. Angewandte Chemie International Edition, 43(39), 5138–5175. https://doi.org/10.1002/anie.200400650
4. Hashimoto, T., & Maruoka, K. (2007). Design of axially chiral dicarboxylic acid for asymmetric Mannich reaction of arylaldehyde N-Boc imines and diazo compounds. Journal of the American Chemical Society, 129(33), 10054–10055. https://doi.org/10.1021/ja073435g
5. He, M., Struble, J. R., & Bode, J. W. (2006). Highly enantioselective azadiene Diels-Alder reactions catalyzed by chiral N-heterocyclic carbenes. Journal of the American Chemical Society, 128(26), 8418–8420. https://doi.org/10.1021/ja062253b
6. Jacobsen, E. N., Pfaltz, A., & Yamamoto, H. (1999). Comprehensive asymmetric catalysis (p. 1178). Springer.
7. Jia, Y. N., Wu, F. C., Ma, X., Zhu, G. J., & Da, C. S. (2009). Highly efficient prolinamide-based organocatalysts for the direct asymmetric Aldol reaction in brine. Tetrahedron Letters, 50(25), 3059–3062. https://doi.org/10.1016/j.tetlet.2009.04.014
8. Kinsella, M., Duggan, P. G., & Lennon, C. M. (2011). Screening of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts for the enantioselective Aldol reaction of acetone with isatin. Tetrahedron: Asymmetry, 22(13), 1423–1433. https://doi.org/10.1016/j.tetasy.2011.07.016

9. Kočovský, P., & Malkov, A. V. (2006). Organocatalysis in the asymmetric Allylation of carbonyl compounds and related reactions. Tetrahedron, 62(3), 55–58. https://doi.org/10.1016/j.tet.2005.09.071
10. Li, H., Wang, Y. Q., & Deng, L. (2006). Enantioselective Friedel–Crafts reaction of indoles with carbonyl compounds catalyzed by bifunctional Cinchona alkaloids. Organic Letters, 8(18), 4063–4065. https://doi.org/10.1021/ol0615228
11. List, B., Lerner, R. A., & Barbas, C. F., III. (2000). Proline-catalyzed direct asymmetric Aldol reactions. Journal of the American Chemical Society, 122(10), 2395–2396. https://doi.org/10.1021/ja994280y
12. McCooey, S. H., & Connon, S. J. (2007). Readily accessible 9-epi-amino Cinchona alkaloid derivatives promote efficient, highly enantioselective additions of aldehydes and ketones to nitroolefins. Organic Letters, 9(4), 599–602. https://doi.org/10.1021/ol062755r
13. Mizuta, S., Shibata, N., Akiti, S., Fujimoto, H., Nakamura, S., & Toru, T. (2007). Cinchona alkaloids/TMAF combination-catalyzed nucleophilic enantioselective trifluoromethylation of aryl ketones. Organic Letters, 9(18), 3707–3710. https://doi.org/10.1021/ol7017215
14. Orlandi, M., Benaglia, M., Raimondi, L., & Celentano, G. (2013). 2-Aminoimidazolyl and 2-aminopyridyl (S)-prolinamides as versatile multifunctional organic catalysts for Aldol, Michael, and Diels–Alder reactions. European Journal of Organic Chemistry, 2013(12), 2346–2354. https://doi.org/10.1002/ejoc.201201643
15. Peng, Y. Y., Ding, Q. P., Li, Z., Wang, P. G., & Cheng, J. P. (2003). Prolinamide catalyzed asymmetric Aldol reaction in aqueous media. Tetrahedron Letters, 44(19), 3871–3875. https://doi.org/10.1016/S0040-4039(03)00713-7
16. Sakthivel, K., Notz, W., Bui, T., & Barbas, C. F., III. (2001). Amino acid catalyzed direct asymmetric Aldol reactions: A bioorganic approach to catalytic asymmetric carbon–carbon bond-forming reactions. Journal of the American Chemical Society, 123(22), 5260–5267. https://doi.org/10.1021/ja010037z
17. Shi, L. X., Sun, Q., Ge, Z. M., Zhu, Y. Q., Cheng, T. M., & Li, R. T. (2004). Dipeptide-catalyzed direct asymmetric Aldol reaction. Synlett, 2004(12), 2215–2217. https://doi.org/10.1055/s-2004-831332
18. Sibi, M. P., & Hasegawa, M. (2007). Organocatalysis in radical chemistry: Enantioselective $\alpha$-oxyamination of aldehydes. Journal of the American Chemical Society, 129(14), 4124–4125. https://doi.org/10.1021/ja068474d
19. Sigman, M. S., Vachal, P., & Jacobsen, E. N. (2000). A general catalyst for the asymmetric Strecker reaction. Angewandte Chemie International Edition, 39(7), 1279–1281. https://doi.org/10.1002/(SICI)1521-3773(20000403)39:7<1279::AID-ANIE1279>3.0.CO;2-U
20. Torii, H., Nakadai, M., Ishihara, K., Saito, S., & Yamamoto, H. (2004). Asymmetric direct Aldol reaction assisted by water and a proline-derived tetrazole catalyst. Angewandte Chemie International Edition, 43(15), 1983–1986. https://doi.org/10.1002/anie.200353412
21. Trost, B. M. (1991). The atom economy—A search for synthetic efficiency. Science, 254(5037), 1471–1477. https://doi.org/10.1126/science.1962206
22. Wang, J., Li, H., Yu, X., Zu, L., & Wang, W. (2005). Chiral binaphthyl-derived amine-thiourea organocatalyst-promoted enantioselective Morita–Baylis–Hillman reaction. Organic Letters, 7(19), 4293–4296. https://doi.org/10.1021/ol0517565
23. Xu, X. Y., Wang, Y. Z., & Gong, L. Z. (2007). Organocatalysts for asymmetric direct syn-Aldol reactions. Organic Letters, 9(22), 4247–4249. https://doi.org/10.1021/ol701831c
24. Yang, H., & Carter, R. G. (2008). N-(p-Dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide: A practical proline mimetic for facilitating enantioselective Aldol reactions. Organic Letters, 10(20), 4649–4652. https://doi.org/10.1021/ol8019316