Day 2 :
University of Coimbra, Portugal
Time : 09:15-09:40
Teresa M V D Pinho e Melo studied Chemistry at the University of Coimbra, where she obtained her PhD in Organic Chemistry in 1995 and received her Habilitation in Organic Chemistry in 2003. She was a Research Fellow at the University of Liverpool (1992-1993). She is currently Director of the Department of Chemistry, Associate Professor with Habilitation and Head of the Organic Chemistry Research Group at the University of Coimbra. She is also President of the Division of Organic Chemistry of the Portuguese Chemical Society. She has published more than 125 peer-reviewed scientific papers in international journals. Her research interests are in the area of synthetic and mechanistic heterocyclic organic chemistry. She is particularly concerned with the development of synthetic routes to new bioactive molecules.
The chemistry of conjugated nitrosoalkenes and azoalkenes, used as electron-deficient heterodienes in hetero-Diels–Alder reactions or as Michael-type acceptors in conjugated 1, 4-addition reactions, has been successfully explored for the synthesis of a plethora of heterocyclic systems (Figure 1). Hetero-Diels–Alder reactions of 3-tetrazolyl- nitrosoalkenes and azoalkenes proved to be an efficient approach to 5-(substituted)-1H-tetrazoles, including tryptophan analogues and β-carbolines bearing the 1H-tetrazol-5-yl substituent. The alkylation of five-membered heterocyclic compounds via reaction with conjugated nitrosoalkenes and azoalkenes was also applied to the functionalization of dipyrromethane and bis(furan-2-yl)methanes. Combining hetero-Diels–Alder reactions of nitroso- and azoalkenes with furans with their ring-opening reactions, the synthesis of novel heterocycles was achieved, namely 6-(2-oxobutyl)-1,6-dihydropyridazines, 6-(2-oxopropyl)-1,6-dihydropyridazines, 5-(3-oxobutyl)-isoxazoles and 5-(3-oxobutyl)-pyrazoles. Base-mediated dehydrohalogenation of α,α-dihalo-oximes and α,α-dihalo-hydrazones in the presence of pyrrole, indole and pyrazoles allowed the development of new routes to dipyrromethanes, bis(indolyl)methanes and bis(pyrazolyl)methanes, respectively. Calix pyrroles and bilanes were also obtained from the reaction of azoalkenes with dipyrromethanes. The study included the biological evaluation of some of the new heterocyles. Further details of this chemistry will be presented and discussed.
1. a) Lopes, S. M. M.; Palacios, F.; Lemos, A.; Pinho e Melo, T. M. V. D. Tetrahedron 2011, 67, 8902. b) Lopes, S. M. M.; Brigas, A. F.; Palacios, F.; Lemos, A.; Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2012, 2152.
2. a) Lopes, S. M. M.; Lemos, A.; Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2014, 7039. b) Nunes, S. C. C.; Lopes, S. M. M.; Gomes, C. S. B.; Lemos, A.; Pais, A. A. C. C.; Pinho e Melo, T. M. V. D. J. Org. Chem. 2014, 79, 10456. c) Jorda, R.; Lopes, S. M. M.; Řezníčková, E.; Kryštof, V.; Pinho e Melo, T. M. V. D. ChemMedChem 2017, 12, 701.
3. a) Lopes, S. M. M.; Henriques, M. S. C.; Paixão, J. A.; Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2015, 6146. b) Alves, A. J. S.; Lopes, S. M. M.; Henriques, M. S. C.; Paixão, J. A.; Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2017, 4011.
4. Pereira, N. A. M.; Lopes, S. M. M.; Lemos, A.; Pinho e Melo, T. M. V. D. Synlett 2014, 25, 423.
5. a) Grosso, C.; Cardoso, A. L.; Lemos, A.; Varela, J.; Rodrigues, M. J.; Custódio, L.; Barreira, L.; Pinho e Melo, T. M. V. D., Eur. J. Med. Chem. 2015, 93, 9. b) Grosso, C.; Cardoso, A. L.; Rodrigues, M. J.; Marques, C.; Barreira, L.; Lemos, A.; Pinho e Melo, T. M. V. D. Bioorganic & Medicinal Chemistry 2017, 25, 1122.
6. Grosso, C.; Lemos, A.; Pinho e Melo, T. M. V. D. Synlett 2014, 25, 2868.
National Taiwan University, Taiwan
Keynote: Mimicking DNA proofreading and repair for stereospecific synthesis of polymers from ladderphane to stromaphane
Time : 09:40-10:05
Self-healing is one of the most important biological processes in which damage triggers an autonomic healing response. DNA repair represents self-healing process at the molecular level. Despite chemical reactions and non-covalent interactions playing a key role on self-healing of polymers and composite materials, the use of self-healing strategy for selective chemical synthesis remains to be explored. We envisioned that this strategy could be borrowed to enhance selectivity or specificity in chemical synthesis. The scheme below summarizes the self-debugging concept that could be executed for the synthesis of a polymer in a specific manner. During the chain growth process (step a), side reaction might take place to intervene the uniformity of the polymeric chain, B-moiety being incorporated to give 2 (step b). The catalytic center at the chain end can immediately take action to sense and eliminate the “intruder” B, in the meantime, to regenerate the active species 3 for further chain growth (step c). In order to give uniform 4, step d for the chain growth from 2 must be much slower than that of step c. We have adopted ROMP of cyclopropene derivative 6 with the first-generation Grubbs catalyst to give the corresponding substituted poly (methylene-vinylene) 7 with all double bonds in trans configuration in addition to cyclohexadiene 8 by-product which can easily be separated from 7. When the second-generation Grubbs catalyst is employed, cyclic polymer 9 with all double bonds in trans-configuration was obtained in addition to 8. Both reactions may basically follow the mechanism shown in the above Scheme. An extension of the ROMP reaction to biscyclopropene has been pursued. A two-dimensional polymer, stromaphane 10 (defined as multiple layers of ladderphanes of which the internal polymeric backbones are shared by two adjacent ladderphane moieties) was obtained.
- For reviews, see: Luh, T.-Y. Acc. Chem. Res. 2013, 46, 378-389. Luh, T.-Y.; Ding, L. Tetrahedron 2017, 73, 0000 (DOI: 10.1016/j.tet/2017.09.29.
- Stroma (from Greek, στρῶμα, or strōma) means “layer“
Central China Normal University, China
Time : 10:05-10:30
Jia-Rong Chen earned his PhD from Central China Normal University (CCNU) under the supervision of Professor Wen-Jing Xiao (2009). After holding a position at CCNU (2009−2010), he worked as a Humboldt Postdoctoral Fellow with Professor Carsten Bolm at the RWTH Aachen University (2011−2012). In 2012, he returned to CCNU and began his independent career an Associate Professor. In July of 2016, he was promoted to Professor of Chemistry. His research interests include asymmetric catalysis, photoredox catalysis and nitrogen radical chemistry. He has received honors and awards including the National Science Fund for Excellent Young Scholars of China (2016), Distinguished Young Scholar of Hubei Province (2016), Thieme Chemistry Journals Award (2015), and Alexander von Humboldt research fellowship (2010)..
Because of the high bond dissociation free energy of the N-H bond, the generation of N-radicals from N-H bonds and their synthetic potential are still underexplored. Recently, the visible-light photocatalysis has emerged as an attractive tool for the catalytic formation of N-centered radicals, but the pre-incorporation of a photolabile groups at the nitrogen atom limited the substrate scope. Recently, we have developed a visible light-induced oxidative deprotonation electron transfer (ODET) strategy for direct conversion of the N-H bonds of hydrazones into the corresponding N-centered radicals. Employing this strategy, we have successfully developed a series of N-radical-based hydroamination, oxyamination of alkenes, as well as cascade reactions. DFT calculations and control experiments were also performed to investigate the reaction mechanisms and regioselectivity. Further details will be presented in the talk.
Figure 1: Visible-light-driven generation and reactions of N-centered radicals
- Chen, J.-R. Hu, X.-Q. Lu, L.-Q. Xiao, W.-J. Chem. Soc. Rev. 2016, 45, 2044-2056.
- Hu, X.-Q.; Chen, J.-R.; Wei, Q.; Liu, F.-L.; Deng, Q.-H.; Beauchemin, A. M.; Xiao, W.-J. Angew. Chem. Int. Ed. 2014, 53, 12163-12167.
- Hu, X.-Q.; Qi, X.; Chen, J.-R.*; Zhao, Q.-Q.; Wei, Q.; Lan, Y.; Xiao, W.-J. Nat. Commun. 2016, 7, 11188.
- Hu, X.-Q.; Chen, J.; Chen, J.-R.; Yan, D.-M.; Xiao, W.-J. Chem. Eur. J. 2016, 22, 14141-14146.
- Zhao, Q.-Q.; Chen, J.; Yan, D.-M.; Chen, J.-R.; Xiao, W.-J. Org. Lett. 2017, 19, 3620-3623.