Brønsted acid catalyzed Morita-Baylis-Hillman reaction: a new mechanistic view for thioureas revealed by ESI-MS(/MS) monitoring and DFT calculations.
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.
Amarante
Giovanni W
GW
Laboratory of Synthesis of Natural Products and Drugs, University of Campinas, UNICAMP, Institute of Chemistry, Department of Organic Chemistry, 13084-971, Campinas, SP, Brazil.
Benassi
Mario
M
Milagre
Humberto M S
HM
Braga
Ataualpa A C
AA
Maseras
Feliu
F
Eberlin
Marcos N
MN
Coelho
Fernando
F
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*
D000143:Acids; D011522:Protons; D013890:Thiourea