title: Brønsted acid catalyzed Morita-Baylis-Hillman reaction: a new mechanistic view for thioureas revealed by ESI-MS(/MS) monitoring and DFT calculations.
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.
authors.affiliation: Laboratory of Synthesis of Natural Products and Drugs, University of Campinas, UNICAMP, Institute of Chemistry, Department of Organic Chemistry, 13084-971, Campinas, SP, Brazil.
authors.forename: Giovanni W
authors.initials: GW
authors.lastname: Amarante
authors.forename: Mario
authors.initials: M
authors.lastname: Benassi
authors.forename: Humberto M S
authors.initials: HM
authors.lastname: Milagre
authors.forename: Ataualpa A C
authors.initials: AA
authors.lastname: Braga
authors.forename: Feliu
authors.initials: F
authors.lastname: Maseras
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
authors.forename: Fernando
authors.initials: F
authors.lastname: Coelho
mesh_terms: D000143:Acids / Q000737:chemistry*; D002384:Catalysis; D003198:Computer Simulation; D006860:Hydrogen Bonding; D007700:Kinetics; D015394:Molecular Structure; D011522:Protons; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D013890:Thiourea / Q000737:chemistry*
chemical_list: D000143:Acids; D011522:Protons; D013890:Thiourea