Photocyclization of Alkenes and Arenes: Penetrating Through Aromatic Armor with the Help of Excited State Antiaromaticity

Abstract

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.

Keywords: antiaromaticity; arenes; photocyclization.

Scheme 1.

Selected effects of aromatic rings on photochemical reactivity.

Scheme 2.

Cis-trans isomerization of double bonds in stilbene and summary of Baird’s rules.

Scheme 3.

The broad substituent scope of the stilbene photocyclization.

Scheme 4.

Mechanism and potential energy surface (PES) for Mallory reaction. Copied with permission from [39].

Scheme 5.

The calculated F* values correlate with the experimental results in Mallory cyclizations. (a) Reactivity of naphthyl-substituted styrene. (b) Competition of steric and electronic factors in more complex substrates.

Scheme 6.

(a) Comparison of I₂ vs. O₂ as oxidants in photocyclization cascades of strained stilbenes. (b) Cyclization of vinylene carbonate under the oxidizing conditions.

Scheme 7.

Rearomatizing by trapping the dihydro intermediate via elimination. Atoms and bonds involved in non-oxidative aromatization are shown in red. (a) Photocyclization of o-OMe-stilbene to phenanthrene. (b) Photocyclization of acetoxy lactone via elimination of acetic acid. (c) Photocyclization of stilbene derivative via elimination of tetrachlorocatechol.

Scheme 8.

Competition of aromatization mechanisms in the photocyclization of 3,4-dihalostyrylnaphthalenes.

Scheme 9.

(a,b) Photocyclizations using base to assist with rearomatization.

Scheme 10.

(a) Free radical arylations in stilbene photocyclization. (b) Example of analogous free radical arylation.

Scheme 11.

Photocyclizations of o-iodo stilbenes. hv = 313 nm. (a) Photocyclization of o-iodonitrostilbene 1.1.22. (b–e) Photocyclization of other o-iodostilbenes. (f) Lack of o-iodo substituent in stilbene 1.1.32 requires addition of I₂ for aromatization to occur.

Scheme 12.

The photocyclization of stilbenes with electron-withdrawing substituents can lead to partial aromatization via 1,3-hydrogen shift. (a) Photocyclization of cyano substituted stilbene. (b) Photocyclization of diphenylmaleic anhydride.

Scheme 13.

Suggested mechanism of prototropic aromatization after photocyclization in methanol.

Scheme 14.

Alkene isomerization in meta-substituted stilbenes.

Scheme 15.

Photocyclizations where oxidant concentration affects selectivity.

Scheme 16.

Oxidative photocyclization in the presence of copper chloride.

Scheme 17.

The effect of n-propylamine in the photocyclization of 1,2-diarylethylene leads to unique product formation.

Scheme 18.

Synthesis of helicenes via oxidative photocyclization of stilbenoids. (a) Photocyclization leading to selective formation of [8]helicene. (b) Photocyclization of 1.2.3 leads to formation of a mixture of two products.

Scheme 19.

Radical-mediated phenyl migration in oxidative photocyclizations.

Scheme 20.

The non-oxidative photocyclization of dianthrone 1.2.14 uses a sacrificial starting material as a hydrogen acceptor for aromatization.

Scheme 21.

Varied oxidative photocyclization of PAHs show varying reactivity with different annelation patterns- (a) the photocyclization fails to proceed for the larger PAH 1.3.1. but occurs for the smaller PAHs 1.3.3 and 1.3.4 (b,c).

Scheme 22.

Photocyclizations of 1-aryl-1,3-butadienes.

Scheme 23.

Diene photocyclization proceeds via H-shifts to form a stable product.

Scheme 24.

Comparison of naphthyl enyne and diene photocyclizations.

Scheme 25.

Phenanthrene formation via the photocyclizations of dienyl naphthalenes.

Scheme 26.

The introduction of heterocyclic units allows naphthalene and carbazole formation with rearomatization via C–X (where X=N, O, S) bond cleavage: (a) variations in the bridge moiety, (b) variations in the terminal hetaryl group.

Scheme 27.

Comparison of regioselectivity of enyne photocyclizations: (a,b) Selective formation of six-membered cycles [89,91], (c) the first indications that five-membered ring formation is possible, (d) complete switch towards the C1–C5 cyclization [90].

Scheme 28.

(a) Effect of triplet sensitization on the ratio of C1–C5 photocyclization of aromatic enynes. (b) Mechanism of C1–C5 cyclization with the loss of formaldehyde. (c) Enyne precursor releases an aldehyde via C1–C5 photocyclization.

Scheme 29.

(Left) Enyne photocyclization diverged into seven-membered ring formation via the addition of O₂. (Right) Enyne cage precursor releases aldehyde via non-oxidative photocyclization.

Scheme 30.

Changes in products in the photocyclization of 2,2′-bis-styrylbiphenyl (300 nm irradiation, quartz vessel, deaerated hexanes). Irradiation times: 15 min (top/a), 6 h (center/b) and 8 h (bottom/b) in the presence of one equivalent of iodine).

Scheme 31.

[2 + 2] cycloaddition in photocyclization of a biphenyl stilbene analog.

Scheme 32.

The photocyclization of 1-styryl biphenyls can lead to either partially (a) or fully (b) aromatized products.

Scheme 33.

Pyrene ring formation via the photocyclization of [2,2]metacyclophane.

Scheme 34.

Non-oxidative photocyclization at the bay region of phenanthrene in the absence of aromatization.

Scheme 35.

(A) Possible pathways of the photocyclization of bis-stilbenes reported by Laarhoven et al. [76,113] and Morgan et al. [19]. (B) The blocking group strategy for the selective synthesis of pyrenes. Note the dual role of blocking groups in the control of Mallory cyclization: directing regioselectivity in the 1st step and preventing this cyclization in the 2nd step.

Scheme 36.

Initial results of bis-stilbene photocyclizations yielding pyrene and chrysene products (adopted with permission from [114]).

Scheme 37.

Presence of weak C–H bonds lead to a cross-over from the photochemical to the radical mechanism.

Scheme 38.

Photocyclizations of N-substituted stilbene analogs. (a) photocyclization of 2-azastilbene 1.6.2. (b) photocyclization of 2-azaphenanthrene 1.6.3. (c) photocyclization of 1-styrylpiridinium cation 1.6.5. (d) photocyclization of styryl pyridine 1.6.7. (e) photocyclization of diazastilbene 1.6.9.

Scheme 39.

Sufficient strain can impede stilbene photocyclization. (a) 5—member ring induces high strain in photocyclization lowering yields. (b) 6—member ring does not induce high strain leading to higher yields than 5—member ring counterpart.

Scheme 40.

Heteroaromatic rings in the bridge do not impede photocyclization in similar nitrogen containing substrates. (a–e) Photocyclizations of complex heteroaromatic substrates containing varying numbers of N- and S-atoms.

Scheme 41.

(a–d) Photocyclizations of selected styrylindoles under oxidative conditions.

Scheme 42.

Competition between two modes of 6π-electrocyclization of 3-(1,2-diarylvinyl)-2-arylimidazo [1,2-a]pyridines.

Scheme 43.

Irradiation of indolylphenylethenes (313 and 365 nm) in the presence of oxidants.

Scheme 44.

Photocyclizations of furan-containing analogs of stilbenes proceed to fully aromatized phenanthrene analogs in the presence of molecular oxygen or iodine: (a) furane at the periphery, (b,c) furane at the core.

Scheme 45.

Thiophenes with expanded polyaromatic systems can participate in stilbene-like photocyclizations: (a) formation of [5]helicene, (b) formation of [7]helicene.

Scheme 46.

Selected reversible photocyclizations of photochromic bis-thiophenes (a,b).

Scheme 47.

Stilbene-like photocyclizations of imines (a,b) and imine analog (c) lead to fully aromatized products.

Scheme 48.

Additives can be used to promote full aromatization in photocyclizations of imine-bridged stilbene analogs.

Scheme 49.

Scope of the stilbene-like photocyclization of B=N analogs.

Scheme 50.

Methyl migration in the photocyclization of B=N analogs of stilbene.

Scheme 51.

Stilbene carbamate selectivity controlled by photocyclization conditions.

Scheme 52.

Stilbene–like photocyclization of a ketone in the presence of an acid.

Scheme 53.

Photocyclization of enolates leads to fully aromatized products from substituted benzenes (a) and biphenyls (b).

Scheme 54.

Photocyclizations of amides attached to aromatic systems: (a) benzenoid, (b) heterocyclic, (c) alkene partners.

Scheme 55.

C-O (a) and C-C (b) bond migration in non-oxidative photocyclizations of amides.

Scheme 56.

Enamide photocyclizations.

Scheme 57.

Photocyclizations of biaryls with N=C=O (a) and N=C (b) moieties.

Scheme 58.

Cyclizations of aryls with a vinyl ether (a) and vinyl sulfide (b) groups.

Scheme 59.

Photocyclization of triarylamines leads to carbazoles. (a) Triarylamines containing one substituent. (b) Triarylamines containing multiple substituents.

Scheme 60.

Divergent cyclizations of unsaturated keto analog.

Scheme 61.

Photocyclization of selenide forming a five-member ring.

Scheme 62.

Cyclization of an aryl vinyl sulfide sensitized by mitchler’s ketone.

Scheme 63.

Photocyclizations of naphthalenes with vinyl (a,b) and thioketone (c) substituents.

Scheme 64.

Summmary of photocyclizations with aromatic precursors.