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Impact of Excited-State Antiaromaticity Relief in a Fundamental Benzene Photoreaction Leading to Substituted Bicyclo[3.1.0]hexenes.
Slanina, Tomás; Ayub, Rabia; Toldo, Josene; Sundell, Johan; Rabten, Wangchuk; Nicaso, Marco; Alabugin, Igor; Fdez Galván, Ignacio; Gupta, Arvind K; Lindh, Roland; Orthaber, Andreas; Lewis, Richard J; Grönberg, Gunnar; Bergman, Joakim; Ottosson, Henrik.
Afiliación
  • Slanina T; Department of Chemistry - Ångström Laboratory, Uppsala University, SE-751 20, Uppsala, Sweden.
  • Ayub R; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo námestí 2, 16610 Prague 6, Czech Republic.
  • Toldo J; Department of Chemistry - Ångström Laboratory, Uppsala University, SE-751 20, Uppsala, Sweden.
  • Sundell J; Department of Chemistry - Ångström Laboratory, Uppsala University, SE-751 20, Uppsala, Sweden.
  • Rabten W; Medicinal Chemistry, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Nicaso M; Department of Chemistry - Ångström Laboratory, Uppsala University, SE-751 20, Uppsala, Sweden.
  • Alabugin I; Department of Chemistry - Ångström Laboratory, Uppsala University, SE-751 20, Uppsala, Sweden.
  • Fdez Galván I; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States.
  • Gupta AK; Department of Chemistry - BMC, Uppsala University, SE-751 23 Uppsala, Sweden.
  • Lindh R; Department of Chemistry - Ångström Laboratory, Uppsala University, SE-751 20, Uppsala, Sweden.
  • Orthaber A; Department of Chemistry - BMC, Uppsala University, SE-751 23 Uppsala, Sweden.
  • Lewis RJ; Uppsala Center for Computational Chemistry - UC3, Uppsala University, SE-751 23 Uppsala Sweden.
  • Grönberg G; Department of Chemistry - Ångström Laboratory, Uppsala University, SE-751 20, Uppsala, Sweden.
  • Bergman J; Medicinal Chemistry, Research and Early Development Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Ottosson H; Medicinal Chemistry, Research and Early Development Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
J Am Chem Soc ; 142(25): 10942-10954, 2020 06 24.
Article en En | MEDLINE | ID: mdl-32456426
ABSTRACT
Benzene exhibits a rich photochemistry which can provide access to complex molecular scaffolds that are difficult to access with reactions in the electronic ground state. While benzene is aromatic in its ground state, it is antiaromatic in its lowest ππ* excited states. Herein, we clarify to what extent relief of excited-state antiaromaticity (ESAA) triggers a fundamental benzene photoreaction the photoinitiated nucleophilic addition of solvent to benzene in acidic media leading to substituted bicyclo[3.1.0]hex-2-enes. The reaction scope was probed experimentally, and it was found that silyl-substituted benzenes provide the most rapid access to bicyclo[3.1.0]hexene derivatives, formed as single isomers with three stereogenic centers in yields up to 75% in one step. Two major mechanism hypotheses, both involving ESAA relief, were explored through quantum chemical calculations and experiments. The first mechanism involves protonation of excited-state benzene and subsequent rearrangement to bicyclo[3.1.0]hexenium cation, trapped by a nucleophile, while the second involves photorearrangement of benzene to benzvalene followed by protonation and nucleophilic addition. Our studies reveal that the second mechanism is operative. We also clarify that similar ESAA relief leads to puckering of S1-state silabenzene and pyridinium ion, where the photorearrangement of the latter is of established synthetic utility. Finally, we identified causes for the limitations of the reaction, information that should be valuable in explorations of similar photoreactions. Taken together, we reveal how the ESAA in benzene and 6π-electron heterocycles trigger photochemical distortions that provide access to complex three-dimensional molecular scaffolds from simple reactants.

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: J Am Chem Soc Año: 2020 Tipo del documento: Article País de afiliación: Suecia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: J Am Chem Soc Año: 2020 Tipo del documento: Article País de afiliación: Suecia