Brønsted Acid Catalyzed Morita–Baylis–Hillman Reaction: A New Mechanistic View for Thioureas Revealed by ESI‐MS(/MS) Monitoring and DFT Calculations |
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| Authors: | Giovanni W Amarante Mario Benassi Humberto M S Milagre Dr Ataualpa A C Braga Dr Feliu Maseras Dr Marcos N Eberlin Dr Fernando Coelho Dr |
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| Institution: | 1. Laboratory of Synthesis of Natural Products and Drugs, University of Campinas, UNICAMP, Institute of Chemistry, Department of Organic Chemistry, 13084‐971, Campinas, SP (Brazil), Fax: (+55)?19‐3521‐3023;2. ThoMSon Mass Spectrometry Laboratory, University of Campinas, UNICAMP, Institute of Chemistry, Department of Organic Chemistry, 13084‐971, Campinas, SP (Brazil), Fax: (+55)?19‐3521‐3073;3. Dept. of Biochemistry and Microbiology, State University of S?o Paulo, 13506‐900, Rio Claro, SP (Brazil);4. Institute of Chemical Research of Catalonia (ICIQ), Av. Pa?sos Catalans, 16, 43007 Tarragona, Catalonia (Spain), Fax: (+34)?977‐920‐231;5. Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia (Spain) |
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| Abstract: | A Morita–Baylis–Hillman (MBH) reaction catalyzed by thiourea was monitored by ESI‐MS(/MS) and key intermediates were intercepted and characterized. These intermediates suggest that thiourea acts as an organocatalyst in all steps of the MBH reaction cycle, including the rate‐limiting proton‐transfer step. DFT calculations, performed for a model MBH reaction between formaldehyde and acrolein with trimethylamine as base and in the presence or the absence of thiourea, suggest that thiourea accelerates MBH reactions by decreasing the transition‐state (TS) energies through bidentate hydrogen bonding throughout the whole catalytic cycle. In the rate‐limiting proton‐transfer step, the thiourea acts not as a proton shuttle, but as a Brønsted acid stabilizing the basic oxygen center that is formed in the TS. |
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| Keywords: | Density functional calculations ESI mass spectrometry Morita– Baylis– Hillman reaction reaction mechanisms thiourea |
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