{rfName}
Im

Indexed in

Citations

102

Altmetrics

Analysis of institutional authors

Nicaso, MarcoAuthor

Share

April 27, 2021
Publications
>
Article
No

Impact of Excited-State Antiaromaticity Relief in a Fundamental Benzene Photoreaction Leading to Substituted Bicyclo[3.1.0]hexenes

Publicated to: Journal Of The American Chemical Society. 142 (25): 10942-10954 - 2020-06-24 142(25), DOI: 10.1021/jacs.9b13769

Authors: Slanina, Tomas; Ayub, Rabia; Toldo, Josene; Sundell, Johan; Rabten, Wangchuk; Nicaso, Marco; Alabugin, Igor; Galvan, Ignacio Fdez; Gupta, Arvind K; Lindh, Roland; Orthaber, Andreas; Lewis, Richard J; Gronberg, Gunnar; Bergman, Joakim; Ottosson, Henrik

Affiliations

AstraZeneca, Med Chem, Res & Early Dev Cardiovasc, Renal & Metab,BioPharmaceut R&D, Gothenburg, Sweden - Author
AstraZeneca, Med Chem, Res & Early Dev Resp, BioPharmaceut R&D,Inflammat & Autoimmune, Gothenburg, Sweden - Author
Czech Acad Sci, Inst Organ Chem & Biochem, Prague 16610 6, Czech Republic - Author
Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA - Author
Uppsala Univ, Dept Chem BMC, SE-75123 Uppsala, Sweden - Author
Uppsala Univ, Dept Chem, Angstrom Lab, SE-75120 Uppsala, Sweden - Author
Uppsala Univ, Uppsala Ctr Computat Chem UC3, SE-75123 Uppsala, Sweden - Author
See more

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 pi pi* 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 S-1-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 6 pi-electron heterocycles trigger photochemical distortions that provide access to complex three-dimensional molecular scaffolds from simple reactants.

Keywords

2,2,2-trifluoroethanolAromaticityBenzvaleneDerivativesEnergyIsomerizationLying electronic statesOrganic-photochemistryPyridinium saltsSinglet

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of The American Chemical Society due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 15/178, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Multidisciplinary. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.31. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-12-06, the following number of citations:

  • WoS: 40
  • Europe PMC: 15

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-06:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 61.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 61 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 16.
  • The number of mentions on the social network X (formerly Twitter): 26 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Czech Republic; Sweden; United States of America.

Awards linked to the item

The Olle Engkvist Byggmastare Foundation is greatly acknowledged for postdoctoral fellowships to T.S., J.T., and W.R. (184-390 and 194-677). T.S. appreciates support from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences and the Czech Grant Academy (19-20467Y). H.O. is grateful to the Swedish Research Council (VR) for financial support (2015-04538 and 2019-05618) and to the Vinnova agency for an academia-industry exchange grant (2016-04572). R.A. is grateful to the Liljewalch Foundation for a travel grant allowing a research visit at FSU. I.A. is grateful for the support by the National Science Foundation (CHE-1465142). R.L. and I.F.G. are grateful to the Swedish Research Council (VR) for financial support (grant 2016-03398). M.N. is grateful for an Erasmus+ scholarship that allowed for a summer internship at UU. The computations were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at the National Supercomputer Center (NSC) in Linkoping and at UPPMAX in Uppsala.