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Heteroatom effect on potential energy topology. A novel reaction mechanism of stereospecific Staudinger synthesis
Institution:1. Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6;2. Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary;3. Egis Pharmaceuticals Plc., Chemical Research Division, PO Box 100, H-1475 Budapest, Hungary;1. Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN 37232, United States;2. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, United States;3. Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States;4. Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN 37232, United States;5. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, United States;6. Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States;1. Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony Sgt. 6, H-6725 Szeged, Hungary;2. Department of Organic Chemistry I, University of the Basque Country, Manuel de Lardizabal 3, E-20018 Donostia, Spain;3. Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada;4. Department of Chemistry, Langelandsgade 140, Aarhus University, DK-8000 Aarhus C, Denmark;1. Centro de Física (CFUM), Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal;2. Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Abstract:The Staudinger synthesis of various β-carbolines and thienopyridines with acetyl chloride derivatives led to novel β-lactam-type fused heterocyclic compounds. The reaction was stereospecific, giving exclusively the cis cycloadducts as racemates. The enthalpy profile and the driving force for the cis-selectivity of this cycloaddition was studied by high level quantum chemical calculations and was assigned to a new effect of the neighbouring heteroatom of the acyl group. In the course of the reaction a new side product was formed supporting the mechanistic results.
Keywords:β-Carbolines  β-Lactams  Staudinger reaction  Stereoselectivity  Mechanism  Heteroatom effect
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