An official website of the United States government
This review focuses on photocyclization reactions involving alkenes and arenes. Photochemistry opens up synthetic opportunities difficult for thermal methods, using light as a versatile tool to convert stable ground-state molecules into their reactive excited counterparts. This difference can be particularly striking for aromatic molecules, which, according to Baird’s rule, transform from highly stable entities into their antiaromatic “evil twins”. We highlight classical reactions, such as the photocyclization of stilbenes, to show how alkenes and aromatic rings can undergo intramolecular cyclizations to form complex structures. When possible, we explain how antiaromaticity develops in excited states and how this can expand synthetic possibilities. The review also examines how factors such as oxidants, substituents, and reaction conditions influence product selectivity, providing useful insights for improving reaction outcomes and demonstrating how photochemical methods can drive the development of new synthetic strategies.
more »
« less
This content will become publicly available on January 8, 2026
Assembly of Pyrenes through a Quadruple Photochemical Cascade: Blocking Groups Allow Diversion from the Double Mallory Path to Photocyclization at the Bay Region
We present a six-step cascade that converts 1,3-distyrylbenzenes (bis-stilbenes) into nonsymmetric pyrenes in 40–60% yields. This sequence merges photochemical steps, E,Z-alkene isomerization, a 6π photochemical electrocyclization (Mallory photocyclization); the new bay region cyclization, with two radical iodine-mediated aromatization steps; and an optional aryl migration. This work illustrates how the inherent challenges of engineering excited state reactivity can be addressed by logical design. An unusual aspect of this cascade is that the same photochemical process (the Mallory reaction) is first promoted and then blocked in different stages within a photochemical cascade. The use of blocking groups is the key feature that makes simple bis-stilbenes suitable substrates for directed double cyclization. While the first stilbene subunit undergoes a classic Mallory photocyclization to form a phenanthrene intermediate, the next ring-forming step is diverted from the conventional Mallory path into a photocyclization of the remaining alkene at the phenanthrene’s bay region. Although earlier literature suggested that this reaction is unfavorable, we achieved this diversion via incorporation of blocking groups to prevent the Mallory photocyclization. The two photocyclizations are assisted by the relief of the excited state antiaromaticity. Reaction selectivity is controlled by substituent effects and the interplay between photochemical and radical reactivity. Furthermore, the introduction of donor substituents at the pendant styrene group can further extend this photochemical cascade through a radical 1,2-aryl migration. Rich photophysical and supramolecular properties of the newly substituted pyrenes illustrate the role of systematic variations in the structure of this classic chromophore for excited state engineering.
more »
« less
- Award ID(s):
- 2102579
- PAR ID:
- 10587672
- Publisher / Repository:
- ACS
- Date Published:
- Journal Name:
- Journal of the American Chemical Society
- Volume:
- 147
- Issue:
- 1
- ISSN:
- 0002-7863
- Page Range / eLocation ID:
- 1074 to 1091
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract An alkoxycarbonyl radical cyclization–cross‐coupling cascade has been developed that allows functionalized γ‐butyrolactones to be prepared in one step from simple tertiary alcohol‐derived homoallylic oxalate precursors. The reaction succeeds with aryl and vinyl electrophiles and is compatible with heterocyclic fragments in both coupling partners. This chemistry allows for the rapid construction of spirolactones, which are of interest in drug discovery endeavors.more » « less
-
Abstract Over the past 50 years, a principal approach to controlling conventional photochemical reactions has relied on imposing geometric constraints on reactant or transition state via conducting photochemistry in the organized or constraining media. Herein, we describe a fundamentally different approach to affect the course of photochemical reactions (photochemical rearrangements) by utilizing spatially selective excitation of specific electronic transitions with plane‐polarized light in the reactant molecules uniformly aligned in the nematic liquid crystal phase. In particular, we focused on the Type B enone rearrangement of 4,4‐diarylcyclohexenones – one of the most common photochemical rearrangements. We demonstrated that the aryl migratory aptitude in this reaction was attenuated in response to changing an angle between the polarization plane of the incident light and the alignment direction of the nematic liquid crystal, with the enhanced aryl migration achieved when the polarization plane coincided with the transition dipole moment leading to the excited state responsible for this migration. The spatially‐selective initial excitation therefore was overruling the electronic factors responsible for the relative ratio of the two alternative photoproducts. The experimental findings were further supported by the results of a computational study. This work showcases a new fundamental paradigm in controlling photochemical reactivity and selectivity of photoreactions.more » « less
-
Abstract A method to rapidly diversify the molecules formed in organic crystals is introduced, with aryl nitriles playing a novel dual role as both hydrogen‐bond acceptors and modifiable organic groups. The discovery of coexisting supramolecular synthons in the same crystal is also described. The general concept is demonstrated by using a bis(aryl nitrile) alkene that undergoes a hydrogen‐bond‐directed intermolecular [2+2] photodimerization to form a tetra(aryl nitrile)cyclobutane. The product is readily converted by click reactivity to a tetra(aryl tetrazole) and by hydrolysis to a tetra(aryl carboxylic acid). The integration of aryl nitriles into solid‐state reactions opens broad avenues to post‐modify products formed in crystalline solids for rapid diversification.more » « less
-
null (Ed.)ABSTRACT Two intermolecular hydroalkenylation reactions of 1,6-enynes are presented which yield substituted 5-membered carbo- and -heterocycles. This reactivity is enabled by a cationic bis-diphenylphosphinopropane (DPPP)CoI species which forms a cobaltacyclopentene intermediate by oxidative cyclization of the enyne. This key species interacts with alkenes in distinct fashion, depending on the identity of the coupling partner to give regiodivergent products. Simple alkenes undergo insertion reactions to furnish 1,3-dienes whereby one of the alkenes is tetrasubstituted. When acrylates are employed as coupling partners, the site of intermolecular C-C formation shifts from the alkyne to the alkene motif of the enyne, yield-ing Z-substituted-acrylate derivatives. Computational studies provide support for our experimental observations and show that the turnover-limiting steps in both reactions are the interactions of the alkenes with the cobaltacyclopentene intermediate via either a 1,2-insertion in the case of ethylene, or an unexpected b-C-H activation in the case of most acrylates. Thus, the H syn to the ester is activated through the coordination of the acrylate carbonyl to the cobaltacycle intermediate, which explains the uncommon Z-selectivity and regiodivergence. Variable time normalization analysis (VTNA) of the kinetic data reveals a dependance upon the concentration of cobalt, acrylate, and activator. A KIE of 2.1 was observed with methyl methacrylate in separate flask experiments, indicating that C-H cleavage is the turnover-limiting step in the catalytic cycle. Lastly, a Hammett study of aryl-substituted enynes yields a rho- value of -0.4, indicating that more electron-rich substituents accelerate the rate of the reaction.more » « less
