Propargylamines belong to a widely studied1 class of building blocks because of their particular molecular skeleton that contains an amine group, suitable for nucleophilic reactions, located in E-position to an alkyne moiety, that can act both as an electrophile and as a source of electrons in nucleophilic reactions.2 Our goal was the development of green and simple Lewis acid catalyzed methodologies to the A3 reaction for the synthesis of primary propargylamines from aldehydes, primary amines and alkynes. In particular, we applied two different Lewis acid catalysts to this reaction: the CuSO4/NaI system in one pot fashion and the CeCl3/CuI system in one pot/two steps way. Figure 1 – CeCl3·7H2O/CuI and CuSO4/NaI catalyzed A3 reaction. Reaction conditions: i) MgSO4, CeCl3·7H2O 30% mol, solventless, N2, r.t., 0.25h. ii) CuI 30% mol, solventless, N2, 40°C iii) CuSO4 30% mol/NaI 60% mol, PhCOOH 5% mol, solventless, N2, 80°C Heptahydrated CeCl3 is a very good catalyst for the formation of imines, widely used also in the synthesis of several classes of organic compounds.3 Its efficacy is enhanced in the presence of inorganic iodides4 and being copper the transition metal of choice for A3 reactions, CuI was used. Also the CuSO4/NaI couple has revealed to be an interesting Lewis acid system, alternative to CeCl3/CuI system. The reaction has been applied also to chiral starting materials and, in general, the amine has no effect on the reaction outcome. Typically CuSO4/NaI catalysed reactions are faster, but suffer of some disadvantages, such as lower yields, and a narrower applicability. The relevant Glaser coupling drawback observed in these conditions has been suppressed by adding some benzoic acid, and has not been observed with the CeCl3/CuI system. References: [1] K. Lauder, A. Toscani, N. Scalacci, D. Castagnolo Chem. Rev. 2017, 117, 14091 – 1420. [2] V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken Chem. Soc. Rev. 2012, 41, 3790 – 3807. [3] R. Properzi, E. Marcantoni Chem. Soc. Rev., 2014, 43, 779 - 791. [4] G. Bartoli, E. Marcantoni, M. Marcolini, L. Sambri Chem. Rev. 2010, 110, 6104 – 6143.

The A3 Coupling Reactions Catalyzed by Efficient Lewis Acid Systems

C. Cimarelli;F. Navazio;F. V. Rossi;G. Lupidi;E. Marcantoni
2018-01-01

Abstract

Propargylamines belong to a widely studied1 class of building blocks because of their particular molecular skeleton that contains an amine group, suitable for nucleophilic reactions, located in E-position to an alkyne moiety, that can act both as an electrophile and as a source of electrons in nucleophilic reactions.2 Our goal was the development of green and simple Lewis acid catalyzed methodologies to the A3 reaction for the synthesis of primary propargylamines from aldehydes, primary amines and alkynes. In particular, we applied two different Lewis acid catalysts to this reaction: the CuSO4/NaI system in one pot fashion and the CeCl3/CuI system in one pot/two steps way. Figure 1 – CeCl3·7H2O/CuI and CuSO4/NaI catalyzed A3 reaction. Reaction conditions: i) MgSO4, CeCl3·7H2O 30% mol, solventless, N2, r.t., 0.25h. ii) CuI 30% mol, solventless, N2, 40°C iii) CuSO4 30% mol/NaI 60% mol, PhCOOH 5% mol, solventless, N2, 80°C Heptahydrated CeCl3 is a very good catalyst for the formation of imines, widely used also in the synthesis of several classes of organic compounds.3 Its efficacy is enhanced in the presence of inorganic iodides4 and being copper the transition metal of choice for A3 reactions, CuI was used. Also the CuSO4/NaI couple has revealed to be an interesting Lewis acid system, alternative to CeCl3/CuI system. The reaction has been applied also to chiral starting materials and, in general, the amine has no effect on the reaction outcome. Typically CuSO4/NaI catalysed reactions are faster, but suffer of some disadvantages, such as lower yields, and a narrower applicability. The relevant Glaser coupling drawback observed in these conditions has been suppressed by adding some benzoic acid, and has not been observed with the CeCl3/CuI system. References: [1] K. Lauder, A. Toscani, N. Scalacci, D. Castagnolo Chem. Rev. 2017, 117, 14091 – 1420. [2] V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken Chem. Soc. Rev. 2012, 41, 3790 – 3807. [3] R. Properzi, E. Marcantoni Chem. Soc. Rev., 2014, 43, 779 - 791. [4] G. Bartoli, E. Marcantoni, M. Marcolini, L. Sambri Chem. Rev. 2010, 110, 6104 – 6143.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/424003
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