Abstract
Cp2TiCl/D2O/Mn is an efficient combination, sustainable and cheap reagent that mediates the D-atom transfer from D2O to different functional groups and can contribute to the synthesis of new deuterated organic compounds under friendly experimental conditions and with great economic advantages.
Introduction
Deuterium is a stable isotope of hydrogen with 0.015% natural abundance broadly used in organic chemistry, pharmacology, organometallic chemistry, spectroscopy and many other fields [1-4]. Exchange of hydrogen for deuterium produces primary and secondary kinetic isotope effects (KIE) causing isotopically substituted molecules to react at different rates (kH ≠ kD). This behaviour is due to the differences in bond dissociation energies for both species, which in turn, is dependent upon the zero point for the vibrational energy of both isotopic molecules. As the mass of deuterium is about twice the mass of hydrogen there is a larger activation energy for the C–D bond dissociation than for the C–H bond [4]. The KIE observed allows multiple applications of the deuterated compound such as the enhancement of the metabolic stability of pharmaceutical drugs, the use of internal standards for mass spectrometry, the elucidation of biosynthetic pathways, and the study of reaction mechanisms and selectivity control reactions.
In an effort to develop efficient procedures for the preparation of deuterated compounds, several methodologies of deuteration have been reported [5]. One of the first procedures reported was the acid- or base-catalyzed exchange of enolizable protons for deuterium. However, in order to achieve high isotopic purities through this procedure, multiple treatments of the enolizable substrate with deuterium oxide are required. Also, this method is not suitable for the incorporation of deuterium at not enolizable positions [6]. Later, the reduction of functional groups using deuterated reagents emerged as a powerful tool for deuteration [7]. The principal disadvantage of the use of reducing agents labelled with deuterium is the high cost of these reagents and the handling of highly flammable substances. The use of palladium metal and D2O is a useful and efficient methodology for H/D exchange in aliphatic and benzylic C–H bonds [8,9]. More recently, organometallic catalysts have been used in the development of methods for deuteration of organic compounds. In this sense, it has been reported that iridium complexes can catalyse the H/D exchange of arenes, cyclic alkenes and vinyl groups [10-12]. Ruthenium complexes catalyse α-deuteration of amines and alcohols [13] and palladium complexes catalyse the ortho-selective deuteration of arenes [14]. Also, SmI2/D2O-mediated the chemoselective synthesis of α,α-dideuterio alcohols directly from carboxylic acid under single-electron-transfer conditions [15]. However, many of these procedures are too specific, being useful only for a particular functional group while the synthesis of the catalysts are very laborious and costly.
Discussion
In this paper we summarize the applications of Cp2TiCl/Mn for the deuteration of organic compounds using D2O as deuterium atom donor.
Cp2TiCl, consists of titanium, one of the most abundant transition metals in the Earth’s crust [16], that can be easily prepared from commercial Cp2TiCl2 by using reductants such as Mn, Zn or Al [17,18], generating in THF, in absence of water a green solution, or a blue one in the presence of water. This complex is a single electron transfer system (SET) that has an unpaired d-electron and a vacant site, allowing heteroatoms with free valence electrons to coordinate and undergo electron transfer through an inner-sphere mechanism to generate carbon radicals or intermediate titanaoxiranes (Scheme 1). This SET is capable of promoting and/or catalyzing several transformations in organic chemistry [17-25]. One of the most relevant transformations is the H/D-atom transfer from H2O/D2O to carbon radicals (pathway A) (obtained from epoxides [26-28], ozonides [29] or activated halides [30] and Cp2TiCl/Mn), to intermediate titanaoxiranes (pathway B) [31,32] (obtained from carbonyl compounds and Cp2TiCl/Mn), and to late transition metals (pathway C) [33] in a process mediated by Cp2TiCl/Mn/H2O or D2O which allows for the reduction of alkenes or alkynes (Scheme 1).
In presence of D2O these radicals (pathway A) can be reduced into deuterated compounds. The reduction can proceed via hydrolysis of an organometallic alkyl-TiIV intermediate (Scheme 2, pathway A1) or via deuterium-atom transfer (DAT) from D2O to radicals (Scheme 2, pathway A2). In the case of the intermediate titanaoxirane (pathway B) D2O could promote the hydrolysis to generate the deuterated compound.
DAT from D2O to radicals can be explained on the basis of the paper reported by Oltra and Rosales et al. [26,27]. In this paper, to explain HATs from water it was proposed that the co-ordination of water to Cp2TiCl might weakens the strength of the O–H bond. In this way a single electron transfer from titanium to oxygen might facilitate the HAT from the titanocene aqua-complex to the free radicals. Theoretical calculations supported that the coordination of water to Cp2TiIIICl weakens the O–H bond, indicating a bond-dissociation energy (BDE) for the intermediate aqua-complex of only 49 kcal/mol. This points to a decrease of almost 60 kcal/mol compared to the calculated BDE of water. Later, Gansäuer et al. proposed a modified structure of the intermediate aqua-complex on the basis of cyclic voltammetry, theoretical calculations and electro-paramagnetic resonance techniques studies [28,34]. These results are in agreement with the previously reported results by Wood et al. [35] and Renaud et al. [36] describing the effect of complexation with a Lewis acid on the strength of the O–H bond in water.
Although more theoretical and experimental studies should be performed to determine the mechanism of reduction of radicals using Cp2TiCl and water, it can be stated that tertiary and hindered radicals are normally reduced via HAT from water in a process mediated by Cp2TiIIICl. Primary and unhindered radicals are normally reduced via hydrolysis of an organometallic alkyl-TiIV intermediate [37].
This HAT or protonation mechanism by Cp2TiCl/D2O/Mn, compared with the single-electron-transfer conditions using SmI2/D2O in the synthesis of α,α-dideuterated alcohols from carboxylic acids, does not require the activation of the organometallic species with base and substoichiometric amounts of Cp2TiCl can be used.
Deuteration of alkenes/alkynes [14] using Cp2TiCl/D2O/Mn and late transition metals (pathway C) was rationalized suggesting that the aqua-complex intermediate could facilitate the DAT from D2O to the late transition metal to give a metal dideuterated species, which accomplishes the deuteration of alkenes/alkynes.
In any case, apart from mechanistic considerations, the Cp2TiCl/D2O/Mn mixture has emerged as an excellent reagent for the deuteration of organic compounds from epoxides [2,27,37], ozonides [29], ketones [31,32], activated halides [30-32], alkenes and alkynes [33]. Several examples are presented in Scheme 3.
The results show that the combination Cp2TiCl/D2O/Mn is able to promote and/or catalyze deuteration of organic compounds by reduction or radical cyclization using reagents that are cheap, abundant and environmentally friendly. Certainly, this new methodology of deuteration will contribute to the synthesis of new deuterated organic compounds with applications as internal standards, pharmaceutical drugs and new materials, among others.
Conclusion
In summary, we presented an overview of the Cp2TiCl/D2O/Mn combination as an efficient, cheap, selective, and sustainable reagent compatible with different functional groups that mediates the deuteration of organic compounds from epoxides, ozonides, carbonyl compounds, activated halides, alkenes and alkynes, under mild and environmentally safe reaction conditions. We foresee that in the near future other complexes of TiIII will be used for the deuteration of organic compounds.
References
-
Gant, T. G. J. Med. Chem. 2014, 57, 3595–3611. doi:10.1021/jm4007998
Return to citation in text: [1] -
Sanderson, K. Nature 2009, 458, 269. doi:10.1038/458269a
Return to citation in text: [1] [2] -
Jiménez, T.; Campaña, A. G.; Bazdi, B.; Paradas, M.; Arráez-Román, D.; Segura-Carretero, A.; Fernández-Gutiérrez, A.; Oltra, J. E.; Robles, R.; Justicia, J.; Cuerva, J. M. Eur. J. Org. Chem. 2010, 22, 4288–4295. doi:10.1002/ejoc.201000487
Return to citation in text: [1] -
Kohen, A.; Limbach, H.-H., Eds. Isotope Effects in Chemistry and Biology; Taylor & Francis, CRC Press: Boca Raton, FL, USA, 2006.
Return to citation in text: [1] [2] -
Atzrodt, J.; Derdau, V.; Fey, T.; Zimmermann, J. Angew. Chem., Int. Ed. 2007, 46, 7744–7765. doi:10.1002/anie.200700039
Return to citation in text: [1] -
Murray, A., III; Williams, D. L. Organic Syntheses with Isotopes; part II; Interscience Publishers: New York-London, 1958.
Return to citation in text: [1] -
Nagaoka, M.; Morio, M.; Numazawa, M. Chem. Pharm. Bull. 1999, 47, 263–266. doi:10.1248/cpb.47.263
Return to citation in text: [1] -
Sajiki, H.; Ito, N.; Esaki, H.; Maesawa, T.; Maegawa, T.; Hirota, K. Tetrahedron Lett. 2005, 46, 6995–6998. doi:10.1016/j.tetlet.2005.08.067
Return to citation in text: [1] -
Sajiki, H.; Aoki, F.; Esaki, H.; Maegawa, T.; Hirota, K. Org. Lett. 2004, 6, 1485–1487. doi:10.1021/ol0496374
Return to citation in text: [1] -
Yung, C. M.; Skaddan, M. B.; Bergman, R. G. J. Am. Chem. Soc. 2004, 126, 13033–13043. doi:10.1021/ja046825g
Return to citation in text: [1] -
Skaddan, M. B.; Yung, C. M.; Bergman, R. G. Org. Lett. 2004, 6, 11–13. doi:10.1021/ol0359923
Return to citation in text: [1] -
Zhou, J.; Hartwig, J. F. Angew. Chem., Int. Ed. 2008, 47, 5783–5787. doi:10.1002/anie.200801992
Return to citation in text: [1] -
Takahashi, M.; Oshima, K.; Matsubara, S. Chem. Lett. 2005, 34, 192–193. doi:10.1246/cl.2005.192
Return to citation in text: [1] -
Ma, S.; Villa, G.; Thuy-Boun, P. S.; Homs, A.; Yu, J.-Q. Angew. Chem., Int. Ed. 2014, 53, 734–737. doi:10.1002/anie.201305388
Return to citation in text: [1] [2] -
Szostak, M.; Spain, M.; Procter, D. J. Org. Lett. 2014, 16, 5052–5055. doi:10.1021/ol502404e
Return to citation in text: [1] -
Ramón, D. J.; Yus, M. Chem. Rev. 2006, 106, 2126–2208. doi:10.1021/cr040698p
Return to citation in text: [1] -
Rosales, A.; Rodríguez-García, I.; Muñoz-Bascón, J.; Roldan-Molina, E.; Padial, N. M.; Pozo Morales, L.; García-Ocaña, M.; Oltra, J. E. Eur. J. Org. Chem. 2015, 21, 4567–4591. doi:10.1002/ejoc.201500292
Return to citation in text: [1] [2] -
Rosales, A.; Rodríguez-García, I.; Muñoz-Bascón, J.; Roldan-Molina, E.; Padial, N. M.; Pozo Morales, L.; García-Ocaña, M.; Oltra, J. E. Eur. J. Org. Chem. 2015, 21, 4592. doi:10.1002/ejoc.201500761
Return to citation in text: [1] [2] -
Nugent, W. A.; RajanBabu, T. V. J. Am. Chem. Soc. 1988, 110, 8561–8562. doi:10.1021/ja00233a051
Return to citation in text: [1] -
Gansäuer, A.; Bluhm, H. Chem. Rev. 2000, 100, 2771–2788. doi:10.1021/cr9902648
Return to citation in text: [1] -
Gansäuer, A.; Rinker, B. Tetrahedron 2002, 58, 7017–7026. doi:10.1016/S0040-4020(02)00697-X
Return to citation in text: [1] -
Gansäuer, A.; Narayan, S. Adv. Synth. Catal. 2002, 344, 465–475. doi:10.1002/1615-4169(200207)344:5<465::AID-ADSC465>3.0.CO;2-I
Return to citation in text: [1] -
Gansäuer, A.; Lauterbach, T.; Narayan, S. Angew. Chem., Int. Ed. 2003, 42, 5556–5573. doi:10.1002/anie.200300583
Return to citation in text: [1] -
Gansäuer, A.; Justicia, J.; Fan, C.-A.; Worgull, D.; Piestert, F. Top. Curr. Chem. 2007, 279, 25–52. doi:10.1007/128_2007_130
Return to citation in text: [1] -
Justicia, J.; Álvarez de Cienfuegos, L.; Campaña, A. G.; Miguel, D.; Jakoby, V.; Gansäuer, A.; Cuerva, J. M. Chem. Soc. Rev. 2011, 40, 3525–3537. doi:10.1039/c0cs00220h
Return to citation in text: [1] -
Barrero, A. F.; Oltra, J. E.; Cuerva, J. M.; Rosales, A. J. Org. Chem. 2002, 67, 2566–2571. doi:10.1021/jo016277e
Return to citation in text: [1] [2] -
Cuerva, J. M.; Campaña, A. G.; Justicia, J.; Rosales, A.; Oller-López, J. L.; Robles, R.; Cárdenas, D. J.; Buñuel, E.; Oltra, J. E. Angew. Chem., Int. Ed. 2006, 45, 5522–5526. doi:10.1002/anie.200600831
Return to citation in text: [1] [2] [3] -
Gansäuer, A.; Behlendorf, M.; Cangönül, A.; Kube, C.; Cuerva, J. M.; Friedrich, J.; van Gastel, M. Angew. Chem., Int. Ed. 2012, 51, 3266–3270. doi:10.1002/anie.201107556
Return to citation in text: [1] [2] -
Rosales, A.; Muñoz-Bascón, J.; López-Sánchez, C.; Álvarez-Corral, M.; Muñoz-Dorado, M.; Rodríguez-García, I.; Oltra, J. E. J. Org. Chem. 2012, 77, 4171–4176. doi:10.1021/jo300344a
Return to citation in text: [1] [2] -
Muñoz-Bascón, J.; Hernández-Cervantes, C.; Padial, N. M.; Álvarez-Corral, M.; Rosales, A.; Rodríguez-García, I.; Oltra, J. E. Chem. – Eur. J. 2014, 20, 801–810. doi:10.1002/chem.201304033
Return to citation in text: [1] [2] -
Barrero, A. F.; Rosales, A.; Cuerva, J. M.; Gansäuer, A.; Oltra, J. E. Tetrahedron Lett. 2003, 44, 1079–1982. doi:10.1016/S0040-4039(02)02703-X
Return to citation in text: [1] [2] [3] -
Rosales, A.; Muñoz-Bascón, J.; Roldan-Molina, E.; Castañeda, M. A.; Padial, N. M.; Gausäuer, A.; Rodríguez-García, I.; Oltra, J. E. J. Org. Chem. 2014, 79, 7672–7676. doi:10.1021/jo501141y
Return to citation in text: [1] [2] [3] -
Campaña, A. G.; Estévez, R. E.; Fuentes, N.; Robles, R.; Cuerva, J. M.; Buñuel, E.; Cárdenas, D.; Oltra, J. E. Org. Lett. 2007, 9, 2195–2198. doi:10.1021/ol070779i
Return to citation in text: [1] [2] -
Gansäuer, A.; Klatte, M.; Brände, G. M.; Friedrich, J. Angew. Chem., Int. Ed. 2012, 51, 8891–8894. doi:10.1002/anie.201202818
Return to citation in text: [1] -
Spiegel, D. A.; Wiberg, K. B.; Schacherer, L. N.; Medeiros, M. R.; Wood, J. L. J. Am. Chem. Soc. 2005, 127, 12513–12515. doi:10.1021/ja052185l
Return to citation in text: [1] -
Pozzi, D.; Scanlan, E. M.; Renaud, P. J. Am. Chem. Soc. 2005, 127, 14204–14205. doi:10.1021/ja055691j
Return to citation in text: [1] -
Gansäuer, A.; Shi, L.; Otte, M.; Huth, I.; Rosales, A.; Sancho-Sanz, I.; Padial, N. M.; Oltra, J. E. Top. Curr. Chem. 2011, 320, 93–120. doi:10.1007/128_2011_124
Return to citation in text: [1] [2]
30. | Muñoz-Bascón, J.; Hernández-Cervantes, C.; Padial, N. M.; Álvarez-Corral, M.; Rosales, A.; Rodríguez-García, I.; Oltra, J. E. Chem. – Eur. J. 2014, 20, 801–810. doi:10.1002/chem.201304033 |
31. | Barrero, A. F.; Rosales, A.; Cuerva, J. M.; Gansäuer, A.; Oltra, J. E. Tetrahedron Lett. 2003, 44, 1079–1982. doi:10.1016/S0040-4039(02)02703-X |
32. | Rosales, A.; Muñoz-Bascón, J.; Roldan-Molina, E.; Castañeda, M. A.; Padial, N. M.; Gausäuer, A.; Rodríguez-García, I.; Oltra, J. E. J. Org. Chem. 2014, 79, 7672–7676. doi:10.1021/jo501141y |
33. | Campaña, A. G.; Estévez, R. E.; Fuentes, N.; Robles, R.; Cuerva, J. M.; Buñuel, E.; Cárdenas, D.; Oltra, J. E. Org. Lett. 2007, 9, 2195–2198. doi:10.1021/ol070779i |
1. | Gant, T. G. J. Med. Chem. 2014, 57, 3595–3611. doi:10.1021/jm4007998 |
2. | Sanderson, K. Nature 2009, 458, 269. doi:10.1038/458269a |
3. | Jiménez, T.; Campaña, A. G.; Bazdi, B.; Paradas, M.; Arráez-Román, D.; Segura-Carretero, A.; Fernández-Gutiérrez, A.; Oltra, J. E.; Robles, R.; Justicia, J.; Cuerva, J. M. Eur. J. Org. Chem. 2010, 22, 4288–4295. doi:10.1002/ejoc.201000487 |
4. | Kohen, A.; Limbach, H.-H., Eds. Isotope Effects in Chemistry and Biology; Taylor & Francis, CRC Press: Boca Raton, FL, USA, 2006. |
7. | Nagaoka, M.; Morio, M.; Numazawa, M. Chem. Pharm. Bull. 1999, 47, 263–266. doi:10.1248/cpb.47.263 |
29. | Rosales, A.; Muñoz-Bascón, J.; López-Sánchez, C.; Álvarez-Corral, M.; Muñoz-Dorado, M.; Rodríguez-García, I.; Oltra, J. E. J. Org. Chem. 2012, 77, 4171–4176. doi:10.1021/jo300344a |
6. | Murray, A., III; Williams, D. L. Organic Syntheses with Isotopes; part II; Interscience Publishers: New York-London, 1958. |
30. | Muñoz-Bascón, J.; Hernández-Cervantes, C.; Padial, N. M.; Álvarez-Corral, M.; Rosales, A.; Rodríguez-García, I.; Oltra, J. E. Chem. – Eur. J. 2014, 20, 801–810. doi:10.1002/chem.201304033 |
5. | Atzrodt, J.; Derdau, V.; Fey, T.; Zimmermann, J. Angew. Chem., Int. Ed. 2007, 46, 7744–7765. doi:10.1002/anie.200700039 |
17. | Rosales, A.; Rodríguez-García, I.; Muñoz-Bascón, J.; Roldan-Molina, E.; Padial, N. M.; Pozo Morales, L.; García-Ocaña, M.; Oltra, J. E. Eur. J. Org. Chem. 2015, 21, 4567–4591. doi:10.1002/ejoc.201500292 |
18. | Rosales, A.; Rodríguez-García, I.; Muñoz-Bascón, J.; Roldan-Molina, E.; Padial, N. M.; Pozo Morales, L.; García-Ocaña, M.; Oltra, J. E. Eur. J. Org. Chem. 2015, 21, 4592. doi:10.1002/ejoc.201500761 |
19. | Nugent, W. A.; RajanBabu, T. V. J. Am. Chem. Soc. 1988, 110, 8561–8562. doi:10.1021/ja00233a051 |
20. | Gansäuer, A.; Bluhm, H. Chem. Rev. 2000, 100, 2771–2788. doi:10.1021/cr9902648 |
21. | Gansäuer, A.; Rinker, B. Tetrahedron 2002, 58, 7017–7026. doi:10.1016/S0040-4020(02)00697-X |
22. | Gansäuer, A.; Narayan, S. Adv. Synth. Catal. 2002, 344, 465–475. doi:10.1002/1615-4169(200207)344:5<465::AID-ADSC465>3.0.CO;2-I |
23. | Gansäuer, A.; Lauterbach, T.; Narayan, S. Angew. Chem., Int. Ed. 2003, 42, 5556–5573. doi:10.1002/anie.200300583 |
24. | Gansäuer, A.; Justicia, J.; Fan, C.-A.; Worgull, D.; Piestert, F. Top. Curr. Chem. 2007, 279, 25–52. doi:10.1007/128_2007_130 |
25. | Justicia, J.; Álvarez de Cienfuegos, L.; Campaña, A. G.; Miguel, D.; Jakoby, V.; Gansäuer, A.; Cuerva, J. M. Chem. Soc. Rev. 2011, 40, 3525–3537. doi:10.1039/c0cs00220h |
4. | Kohen, A.; Limbach, H.-H., Eds. Isotope Effects in Chemistry and Biology; Taylor & Francis, CRC Press: Boca Raton, FL, USA, 2006. |
26. | Barrero, A. F.; Oltra, J. E.; Cuerva, J. M.; Rosales, A. J. Org. Chem. 2002, 67, 2566–2571. doi:10.1021/jo016277e |
27. | Cuerva, J. M.; Campaña, A. G.; Justicia, J.; Rosales, A.; Oller-López, J. L.; Robles, R.; Cárdenas, D. J.; Buñuel, E.; Oltra, J. E. Angew. Chem., Int. Ed. 2006, 45, 5522–5526. doi:10.1002/anie.200600831 |
28. | Gansäuer, A.; Behlendorf, M.; Cangönül, A.; Kube, C.; Cuerva, J. M.; Friedrich, J.; van Gastel, M. Angew. Chem., Int. Ed. 2012, 51, 3266–3270. doi:10.1002/anie.201107556 |
14. | Ma, S.; Villa, G.; Thuy-Boun, P. S.; Homs, A.; Yu, J.-Q. Angew. Chem., Int. Ed. 2014, 53, 734–737. doi:10.1002/anie.201305388 |
13. | Takahashi, M.; Oshima, K.; Matsubara, S. Chem. Lett. 2005, 34, 192–193. doi:10.1246/cl.2005.192 |
17. | Rosales, A.; Rodríguez-García, I.; Muñoz-Bascón, J.; Roldan-Molina, E.; Padial, N. M.; Pozo Morales, L.; García-Ocaña, M.; Oltra, J. E. Eur. J. Org. Chem. 2015, 21, 4567–4591. doi:10.1002/ejoc.201500292 |
18. | Rosales, A.; Rodríguez-García, I.; Muñoz-Bascón, J.; Roldan-Molina, E.; Padial, N. M.; Pozo Morales, L.; García-Ocaña, M.; Oltra, J. E. Eur. J. Org. Chem. 2015, 21, 4592. doi:10.1002/ejoc.201500761 |
10. | Yung, C. M.; Skaddan, M. B.; Bergman, R. G. J. Am. Chem. Soc. 2004, 126, 13033–13043. doi:10.1021/ja046825g |
11. | Skaddan, M. B.; Yung, C. M.; Bergman, R. G. Org. Lett. 2004, 6, 11–13. doi:10.1021/ol0359923 |
12. | Zhou, J.; Hartwig, J. F. Angew. Chem., Int. Ed. 2008, 47, 5783–5787. doi:10.1002/anie.200801992 |
8. | Sajiki, H.; Ito, N.; Esaki, H.; Maesawa, T.; Maegawa, T.; Hirota, K. Tetrahedron Lett. 2005, 46, 6995–6998. doi:10.1016/j.tetlet.2005.08.067 |
9. | Sajiki, H.; Aoki, F.; Esaki, H.; Maegawa, T.; Hirota, K. Org. Lett. 2004, 6, 1485–1487. doi:10.1021/ol0496374 |
15. | Szostak, M.; Spain, M.; Procter, D. J. Org. Lett. 2014, 16, 5052–5055. doi:10.1021/ol502404e |
26. | Barrero, A. F.; Oltra, J. E.; Cuerva, J. M.; Rosales, A. J. Org. Chem. 2002, 67, 2566–2571. doi:10.1021/jo016277e |
27. | Cuerva, J. M.; Campaña, A. G.; Justicia, J.; Rosales, A.; Oller-López, J. L.; Robles, R.; Cárdenas, D. J.; Buñuel, E.; Oltra, J. E. Angew. Chem., Int. Ed. 2006, 45, 5522–5526. doi:10.1002/anie.200600831 |
31. | Barrero, A. F.; Rosales, A.; Cuerva, J. M.; Gansäuer, A.; Oltra, J. E. Tetrahedron Lett. 2003, 44, 1079–1982. doi:10.1016/S0040-4039(02)02703-X |
32. | Rosales, A.; Muñoz-Bascón, J.; Roldan-Molina, E.; Castañeda, M. A.; Padial, N. M.; Gausäuer, A.; Rodríguez-García, I.; Oltra, J. E. J. Org. Chem. 2014, 79, 7672–7676. doi:10.1021/jo501141y |
33. | Campaña, A. G.; Estévez, R. E.; Fuentes, N.; Robles, R.; Cuerva, J. M.; Buñuel, E.; Cárdenas, D.; Oltra, J. E. Org. Lett. 2007, 9, 2195–2198. doi:10.1021/ol070779i |
29. | Rosales, A.; Muñoz-Bascón, J.; López-Sánchez, C.; Álvarez-Corral, M.; Muñoz-Dorado, M.; Rodríguez-García, I.; Oltra, J. E. J. Org. Chem. 2012, 77, 4171–4176. doi:10.1021/jo300344a |
31. | Barrero, A. F.; Rosales, A.; Cuerva, J. M.; Gansäuer, A.; Oltra, J. E. Tetrahedron Lett. 2003, 44, 1079–1982. doi:10.1016/S0040-4039(02)02703-X |
32. | Rosales, A.; Muñoz-Bascón, J.; Roldan-Molina, E.; Castañeda, M. A.; Padial, N. M.; Gausäuer, A.; Rodríguez-García, I.; Oltra, J. E. J. Org. Chem. 2014, 79, 7672–7676. doi:10.1021/jo501141y |
14. | Ma, S.; Villa, G.; Thuy-Boun, P. S.; Homs, A.; Yu, J.-Q. Angew. Chem., Int. Ed. 2014, 53, 734–737. doi:10.1002/anie.201305388 |
2. | Sanderson, K. Nature 2009, 458, 269. doi:10.1038/458269a |
27. | Cuerva, J. M.; Campaña, A. G.; Justicia, J.; Rosales, A.; Oller-López, J. L.; Robles, R.; Cárdenas, D. J.; Buñuel, E.; Oltra, J. E. Angew. Chem., Int. Ed. 2006, 45, 5522–5526. doi:10.1002/anie.200600831 |
37. | Gansäuer, A.; Shi, L.; Otte, M.; Huth, I.; Rosales, A.; Sancho-Sanz, I.; Padial, N. M.; Oltra, J. E. Top. Curr. Chem. 2011, 320, 93–120. doi:10.1007/128_2011_124 |
36. | Pozzi, D.; Scanlan, E. M.; Renaud, P. J. Am. Chem. Soc. 2005, 127, 14204–14205. doi:10.1021/ja055691j |
37. | Gansäuer, A.; Shi, L.; Otte, M.; Huth, I.; Rosales, A.; Sancho-Sanz, I.; Padial, N. M.; Oltra, J. E. Top. Curr. Chem. 2011, 320, 93–120. doi:10.1007/128_2011_124 |
28. | Gansäuer, A.; Behlendorf, M.; Cangönül, A.; Kube, C.; Cuerva, J. M.; Friedrich, J.; van Gastel, M. Angew. Chem., Int. Ed. 2012, 51, 3266–3270. doi:10.1002/anie.201107556 |
34. | Gansäuer, A.; Klatte, M.; Brände, G. M.; Friedrich, J. Angew. Chem., Int. Ed. 2012, 51, 8891–8894. doi:10.1002/anie.201202818 |
35. | Spiegel, D. A.; Wiberg, K. B.; Schacherer, L. N.; Medeiros, M. R.; Wood, J. L. J. Am. Chem. Soc. 2005, 127, 12513–12515. doi:10.1021/ja052185l |
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