Cyclopropenes in Photochemical Reactions

ABSTRACT

This review covers the reactivity of cyclopropenes under light irradiation. Cyclopropenes have a formidable and complex photochemistry. While fundamental photochemistry of cyclopropenes was early studied, the synthetic potential has not been developed at comparable pace as synthetic photochemistry has recently evolved. In this review, the main types of light‐mediated reactivity of cyclopropenes is briefly presented and focus on the synthetic possibilities offered by these reactions. Moreover, photochemical reactions in which cyclopropenes at ground state react with other photo‐excited molecules are also presented. Finally, the value of cyclopropenes in a different field as light‐mediated bio‐orthogonal reactions is succinctly introduced.

The photochemical side of cyclopropenes. Cyclopropenes are valuable synthetic tools in organic chemistry. In particular, this review focuses on the photochemistry of cyclopropenes. The reactivity of cyclopropenes excited by irradiation is discussed showing their unique potential for organic synthesis. Moreover, reactions of cyclopropenes at ground state with other photo‐excited molecules is also presented, including recent applications in bioorthogonal reactions.

1. Introduction

As brilliantly described by Roth, the use of light has from early times fascinated scientists [1]. The end of the 19^th century is normally considered the birth of photochemistry as scientific discipline. During the second half of the 20^th century, the development of modern organic photochemistry led to the discovery of new fundamental reactivity, which is not accessible through ground state chemistry [2, 3, 4]. However, complexity of organic photochemistry and the need of specialized equipment operating with high‐energy light limited its application in organic synthesis. In the last two decades, the development of reactions accomplished by irradiation with more convenient visible light in the presence of suitable metal or organic photocatalysts has contributed to the renaissance of organic photochemistry [5, 6]. Indeed, the catalogue of photochemical transformations and its synthetic utility is increasing at an astonishing speed.

Besides, the beauty of exotic molecules captivates chemists. In this regard, cyclopropenes were already postulated during 19^th century, although their existence was still not demonstrated [7, 8]. Later, Dem'yanov and Doyarenko reported in 1921 the first low‐yielding synthesis of cyclopropene itself, which showed limited stability [9, 10]. The lack of synthetic methods and the alleged instability of cyclopropenes provoked that they were overlooked until the late 1950s. At that time, studies concerning cyclopropene rearrangements [11], aromaticity of the cyclopropenyl cation [12], or the isolation of natural products containing cyclopropene rings in their structures [13, 14],] led to the development of the chemistry of cyclopropenes during the next decades. From the first revision in 1964 [15], several comprehensive text [16, 17] and review‐devoted journals have covered several aspects of cyclopropene chemistry [18, 19, 20, 21, 22].

In spite of the interesting early studies dealing with the photochemistry of cyclopropenes, and the recent interest of photochemistry in organic synthesis, a revision dedicated to cyclopropenes in photochemical reactions has not been disclosed, with the exception of an excellent account presented by Prof. A. Padwa in 1979 [23]. This revision aims to provide with an update on the advances in the use of photochemistry with cyclopropenes and, hopefully, trigger further developments. As simple organization, this review is divided by considering two distinctive processes, those in which the cyclopropene is directly excited by irradiation and those in which the cyclopropene reacts with a light‐excited molecule (Scheme 1). We describe the selected literature from the perspective of synthetic methodology, however, information about the mechanism is also included where appropriate. It should be noticed that cyclopropenes could be prepared using photochemistry, however, this reactivity is not included in this revision.

SCHEME 1.

Photochemical reactions involving cyclopropenes.

2. Photochemistry of Cyclopropenes

2.1. General Features of Cyclopropenes in the Excited State

The main feature of cyclopropenes is the large strain energy, which is greater than 200 kJ mol–¹ (228 kJ mol⁻¹ for cyclopropene itself) [24]. However, a high activation energy barrier of near 140 kJ mol⁻¹ [25], makes cyclopropenes reluctant to undergo ring‐opening reactions in the absence of other reagents. As a result, direct cleavage of cyclopropenes requires high temperatures or the irradiation to an excited state. Due to its particular structure, the thermal and photochemical reactivity of simple cyclopropenes is more complex than the observed for alkenes or alkynes, since a variety of intermediates are available (1,3‐diradicals, carbenes or vinylidenes) and might follow divergent reaction pathways (Scheme 2A) [26, 27, 28, 29, 30, 31]. A representative example of thermal and photochemical unimolecular reactions of cyclopropene 1 is depicted to illustrate this fact (Scheme 2B) [32]. Indeed, alkyne 2 was the major product under thermal conditions. However, a mixture of alkyne 2, allene 3 and 1,3‐diene 4 with low selectivity was observed after direct irradiation with far UV‐light. This behavior seems to be common for alkyl substituted cyclopropenes [33, 34].

SCHEME 2.

Thermal vs photochemical reactivity of simple cyclopropenes.

A basic scenario describing the thermal (ground state) and photochemical (excited state) reactivity of cyclopropenes is shown in Scheme 3. In the ground state, the thermal reaction proceeds via a homolytic σ‐C–C‐bond cleavage leading to a singlet 1,3‐diradical intermediate, which rapidly evolves to a more stable singlet carbene intermediate. Eventually, vinylidene intermediates have also been proposed [35, 36, 37, 38]. Similarly, the direct irradiation of cyclopropene to an excited singlet state also correlates with a singlet vinyl carbene in the ground state. However, by photochemical activation, the electronic configuration of the carbene might be different leading to dissimilar results (Scheme 3A). It should be noticed that in spite of the strain release, reactions in the singlet excited state show low quantum efficiency since the carbene intermediate easily reverts to the cyclopropene via nonradiative process [39]. In sharp contrast, the sensitized irradiation of cyclopropenes leads to a ³ ππ* diradical triplet excited‐state, as it is the case of normal alkenes. In spite of the ring strain and the energy provided by the irradiation, this triplet state generally evolves through processes that retain the cyclopropane ring.

SCHEME 3.

Excited states of cyclopropenes: General reactivity and supporting evidences.

Some selected examples are given as support for this basic mechanistic situation. The participation of carbenes as intermediates in photochemical direct irradiation was early demonstrated by Arnold and Pincock in a series of studies (Scheme 3B) [36, 40, 41]. Thus, the direct irradiation (> 350 nm) of cyclopropene 5 in the presence of methanol led to mixture of methyl ether derivatives 6 and 7, along with 1,3‐dienes 8 and 9. The formation of all these products could be explained from a unique common carbene intermediate. Moreover, the low quantum yield was indicative for the return of the carbene intermediate to the starting cyclopropene. The photochemical racemization of cyclopropene 10, which occurred faster than other expected photo‐rearrangements, also supported the participation of vinyl carbene intermediates derived from singlet excited state and the reversibility of the reaction (Scheme 3C) [42]. In sharp contrast, the irradiation of (R)‐10 using acetone as sensitizer led to the dimerization product 11, whose formation is the result of the dimerization of typical ³ ππ* diradical triplet excited state intermediates [42, 43].

The simplicity of the reactivity of cyclopropenes in the excited state shown in Scheme 3 is merely apparent. Indeed, in addition to the typical difficulties associated with photochemical reactions, the substitution pattern strongly influences the reaction outcome. As a result, a systematic organization of the photochemistry of cyclopropenes is far from easy and, after showing pioneering examples of cyclopropene photochemistry, a mixed approach based on the substitution pattern of the cyclopropane as well as the reaction types are used along this review.

2.2. Early Discoveries on the Photochemistry of Cyclopropenes

The first studies on the photochemistry of cyclopropenes were accomplished in the 1960s. These early exploratory works already set the fundamentals of cyclopropene photochemistry and showed its potential in synthetic chemistry, which surprisingly has not been fully exploited. Specifically, Stechl reported in 1963 the dimerization of cyclopropene 12 by UV‐light irradiation (high‐pressure Hg lamp) using benzophenone as sensitizer to afford a regioisomeric mixture of tricycles 13 and 14, which after heating led to durene (15) (Scheme 4A) [44, 45]. This reactivity was subsequently also observed by Moritani using cyclopropene 16 [46], which by intramolecular sensitization with UV‐light in THF at 65°C led to 1,2,4,5‐tetraphenylbenzene (17) in moderate yield (Scheme 4B). Interestingly, in the case of cyclopropene 18, the participation of tricycle 19 was demonstrated as it could be isolated. Further irradiation of 19 under the same conditions afforded again the arene 17. Besides, Breslow reported the photoisomerization of 3,3’‐bicyclopropene derivative 21 by direct UV‐light irradiation (Scheme 4C) [47]. Under these conditions hexaphenylbenzene (22) was obtained in an impressive 80% yield. Additionally, Breslow also provided evidences on the participation of Ladenburg and Dewar benzene intermediates in this remarkable transformation [48].

SCHEME 4.

Early studies on the photochemistry of cyclopropenes.

These works served to trigger the interest in the photochemistry of cyclopropenes and, subsequently, more studies were conducted in order to know their fundamental photochemistry and reactivity.

2.3. Light‐mediated Isomerizations of Aryl‐, Vinyl‐ and Allyl‐Substituted Cyclopropenes

The isomerization of in‐situ generated 3‐phenyl‐substituted cyclopropenes to afford indenes was reported in 1966 [49, 50]. Afterwards, studies using the corresponding isolated cyclopropenes were accomplished by Padwa [51], Stoffer [52], and others [53]. The photo‐rearrangement of these compounds, as illustrated with cyclopropane 23, leads to indene derivatives as a mixture of isomers (Scheme 5A), limiting the synthetic interest of the reaction. It should be noticed that thermal rearrangement of these type of cyclopropenes also leads to indenes, but the observed differences in the regioselectivity indicate that different cleavages of the cyclopropenes take place depending on the reaction conditions. Mechanistic studies, including trapping experiments with methanol, indicate that a vinyl carbene might be and intermediate of the reaction. It also noteworthy that the composition of the mixture depends on the irradiation time and it was demonstrated that indenes 24 and 25 are photolabile and they are each converted into the other. Interestingly, the irradiation of the same cyclopropene using 9,10‐dicyanoanthracene (DCA) as sensitizer led to a unique indene 25 along with the formation of naphthalene 26 (Scheme 5B) [54]. In this case, the sensitization process involveds a SET process to generate a radical cation intermediate, which evolves to 25 and 26, according to the alkene stereochemistry of the intermediate.

SCHEME 5.

Representative examples of photoisomerization reactions of 3‐aryl‐substituted cyclopropenes.

The analogous reaction using 3‐heteroaryl‐substituted cyclopropenes was reported immediately afterwards by Padwa, Chiacchio and co‐workers (Scheme 6) [55, 56]. Direct irradiation with a 450‐W Hanovia mercury lamp (Pyrex) of a benzene solution containing furan‐, pyrrole‐ or thiophene‐substituted cyclopropenes 27, led to the formation of a mixture of the corresponding bicyclic derivatives 28 and 29 (Scheme 6A). It should be noticed that the presence of methyl substituents in the heteroarene resulted in less selective reactions since by products derived from cyclopropene ring‐opening and isomerizations were also perceptible. These reactions were proposed to occur via carbene intermediate generated by irradiation and subsequent electrocyclization.

SCHEME 6.

Photoisomerization of 3‐heterocyclic‐substituted cyclopropenes.

Padwa and co‐workers also studied the reactivity of cyclopropenes decorated with oxazolinones at the position 3 (Scheme 6B) [57]. A typical rearrangement of cyclopropene 30 to the indene 31, without the participation of the heterocycle, was observed in this case. Interestingly, the thermal reaction of the same cyclopropene lead to pyridine 32 after CO₂ extrusion.

In similar fashion, the photochemistry of 3‐vinyl‐substituted cyclopropenes was intensively investigated concurrently by Zimmermann's [58, 59] and Padwa's [60, 61, 62] groups during the late 1970s. Both described the photoisomerization by direct irradiation (Pyrex filter) of 3‐vinyl‐1,2‐diphenylcyclopropenes 33 and 35 to the corresponding cyclopentadienes 34 and 36, respectively, with a broad range of yields (Scheme 7). A long‐standing mechanistic discussion followed these discoveries [63, 64, 65, 66, 67]. Without entering in details, the most likely intermediate was proposed to be a diradical species, rather than a carbene‐like intermediate. Unfortunately, the introduction of two different substituents at the positions 1 and 2 of the cyclopropene led to mixtures of regioisomers, therefore, limiting its synthetic utility.

SCHEME 7.

Representative examples of photoisomerization reactions of 3‐vinyl‐substituted cyclopropenes.

A particular class of 3‐vinyl‐substituted cyclopropenes, namely 1,3’‐bicyclopropene derivatives, was studied by Padwa and co‐workers (Scheme 8) [68]. In contrast to 3,3’‐bicyclopropenes reported earlier by Breslow [47], irradiation of 1,3’‐bicyclopropene 37 in benzene with UV light led to the formation of naphthalene derivative 38 in good yield. The transformation was proposed to occur via carbene intermediate followed by a series of rearrangements, although an experimental evidence was not provided.

SCHEME 8.

Photoisomerization reactions of 1,3’‐bicyclopropenyls.

In simultaneous studies, the groups of Padwa [69, 70, 71, 72] and Zimmerman [73] also described the reactivity of 3‐allyl‐substituted cyclopropenes. The influence of the substituents on the reactivity is again evident considering the different outcomes in the reaction of constitutional isomeric cyclopropenes 39 and 41 (Scheme 9). Thus, direct irradiation of 39 in benzene (Pyrex filter) led to bicyclic compound 40 (65%) through a cyclopropanation via carbene intermediate. In contrast, cyclopropene 41 gave rise to a mixture of indenes 42 and 43 as a consequence of the two possible C–C‐bond cleavages, without the involvement of the alkene. In this case, the authors suggested that E/Z‐isomerization of carbene intermediates and indene formation should be notably faster than the cyclopropanation. Moreover, the use of DCA as sensitized gave solely rise to indene 42 through a mechanism involving SET process similar as the one indicated in Scheme 5 [54].

SCHEME 9.

Representative examples of photoisomerization reactions of 3‐allyl‐substituted cyclopropenes.

In contrast to the previous studies, a more recent report by Shi and co‐workers in 2009 dealt with the use of 2‐vinyl‐substituted cyclopropenes 44 (Scheme 10) [74]. Here, the direct UV irradiation (Pyrex) of cyclopropenes 44 led to the formation of azulene derivatives 45 in good yields, instead of the typical indene formation. A remarkable scope of this photochemical transformation was presented, yet unsymmetrically substituted cyclopropenes led, as expected, to almost equimolecular amount of regioisomers. In this process, the direct irradiation enabled the excitation of cyclopropenes with a subsequent regioselective ring‐cleavage of the less‐strained σ‐C–C bond to form a carbene intermediate. However, this species underwent a Büchner‐type insertion into the aromatic ring via cyclopropanation/ring‐expansion to form the corresponding azulenes. The singlet or triplet nature of the carbene is still unknown since direct and photosensitized irradiation led to the same results.

SCHEME 10.

Photoisomerization reactions of 2‐vinyl‐substituted cyclopropenes.

2.4. Light‐mediated Reactions of 3‐Acyl‐Substituted Cyclopropenes and Related Compounds

The photochemistry of 3‐acylcyclopropenes was reported in 1982 by Padwa and co‐workers [75]. In particular, the direct irradiation of cyclopropene 46 (450 W Hanovia lamp, Pyrex filter) led to a mixture of products 47–49, whose formation involved the expected vinyl carbene intermediate with different stereochemistry (Scheme 11A). Later, Zimmerman and co‐workers performed the irradiation of cyclopropene 46 in the presence of thioxanthone as sensitizer (Scheme 11B) [76, 77]. In this case, the reaction was completely selective toward furan 49. The same reactivity was shown by 3‐iminocyclopropene 50, which afforded tetrasubstituted pyrrole 51. The potential synthetic value of this method to prepare polysubstituted furans is hampered by the fact that the use of unsymmetrical cyclopropenes resulted in the unselective formation of regioisomers. This fact is confirmed by comparing the reaction of cyclopropenes 52 and 53. Under sensitized conditions, a ³(nπ*) triplet state of the cyclopropene likely evolves to oxahousane biradical intermediate, followed by the cleavage of the internal σ‐C–C‐bond. It should be noticed that this reactivity of the triplet state in 3‐acylcyclopropenes is restricted to cyclopropenes bearing an aryl group at the position 3 [77, 78].

SCHEME 11.

Photochemistry of 3‐acyl‐ and 3‐iminyl‐cyclopropenes.

The photochemistry of (cyclopropenylcarbonyloxy)phthalimides was disclosed by Joglar and co‐workers in 1998. By using n‐Bu₃SnH under irradiation with UV light (150 high‐pressure Hg lamp, Pyrex filter), cyclopropene 57 experienced a decarboxylation and radical coupling with phthalimide radical to afford cyclopropene 58 (Scheme 12A) [79]. The participation of a transient cyclopropenyl radical was demonstrated by trapping with an aminoxyl radical 59 as scavenger, although the role of the n‐Bu₃SnH was not explained [80].

SCHEME 12.

Photochemistry of (cyclopropenylcarbonyloxy)phthalimides.

]The exploitation of this type of reactivity with synthetic purposes was described more recently by Waser and co‐workers (Scheme 12B) [81]. The convenient use of visible blue LED light employing 1,3‐dicyano‐2,4,5,6‐tetrakis(diphenylamino)‐benzene (4DPAIPN) as photocatalyst served to convert tetrasubstituted cyclopropenyl phthalimides 60 into the corresponding 3‐phthalimide‐substituted cyclopropenes 61, via formal decarboxylation. Moreover, the use of analogous trisubstituted cyclopropenes 62 led to the formation of new cyclopropenes 63, by replacing the 3‐phthalimido group with a suitable nucleophile. Under this conditions, the excited photocatalyst is oxidized by the cyclopropene via SET process to generate the corresponding cyclopropenyl radical anion species. A subsequent decarboxylation and loss of phthalimide led to a cyclopropenyl radical intermediate. This radical acts as the reductant for photocatalyst turnover and lead to an aromatic cyclopropenium cation intermediate. Considering this mechanistic scenario, the authors were able to trap the cationic intermediate with a variety of nucleophiles, including the use of several organotrifluoroborates among others.

2.5. Light‐mediated H‐Abstraction From Excited Cyclopropenes

Hydrogen abstraction processes are common in radical reactions. In the case of cyclopropenes, this reactivity pattern was reported by Padwa and co‐workers in 1978 (Scheme 13) [82, 83]. The sensitized irradiation (thioxanthone) of cyclopropene 64 with 450‐W mercury lamp equipped with a Pyrex filter, led to the formation of cis‐cyclopropane 65 and bicyclo[3.1.0]hexane derivative 66 (Scheme 13A). The proposed mechanism involved the generation of the excited triplet of the cyclopropene, which was capable of performing a hydrogen abstraction from γ‐carbon atom via 6‐membered transition state to generate a new 1,5‐biradical. Finally, a biradical coupling or a radical disproportionation explain the formation of both products. The lack of reactivity shown in cyclopropenes without hydrogen atom at γ‐position supports the mechanism. The reaction outcome is sensitive to the substituents of the cyclopropene and the surrounding of the γ‐carbon, but only in some cases is selective. Thus, using cyclopropenes bearing an arene between the γ‐carbon and the cyclopropene led to the formation of cyclic products, as illustrated with compound 68 (Scheme 13B) [84, 85, 86, 87]. This transformation is also applicable to suitable 2‐alkyl‐substituted cyclopropenes as demonstrated with the reaction of cyclopropene 69 to form spiro compound 70 (Scheme 13B). Moreover, when tethering between cyclopropene and γ‐carbon contains a heteroatom, as for cyclopropenes 71 and 73, the biradical coupling products were also selectively obtained, as depicted with the preparation of bicycles 72 and 74 (Scheme 13C) [88]. On the contrary, cyclopropenes showing longer alkyl chains, such as 75, led to the formation of the corresponding alkene 76 via radical disproportionation and the use of D‐labelled cyclopropene 77 affording cyclopropane 78 served as a strong indication of an initial 1,5‐H migration (Scheme 13D) [87, 88].

SCHEME 13.

Light‐mediated reactions involving a H‐abstraction from excited cyclopropenes.

A mechanistically differentiated reaction was reported by Khomoto and co‐workers (Scheme 13C) [89]. This transformation was accomplished with cyclopropenes 79 bearing a remote alkene, which under irradiation with a 400 W high pressure mercury lamp (Pyrex) or in the presence of triplet sensitizers at 366 nm, afforded spirocyclic compounds 80 in good yields. In this case, the order of the events is inverted. Thus, the photo‐excitation of the cyclopropenes 79 lacking γ‐H‐atoms is followed by a cyclization with the alkene, as it is the case of light‐mediated [2+2]‐cycloadditions (see below). However, the produced 1,4‐biradical intermediate contains now a γ‐H‐atom and evolves through a radical disproportionation via 1,5‐H‐abstraction instead of the biradical coupling.

2.6. [2+2]‐Photocycloadditions of Cyclopropenes

As indicated above, dimerization via [2+2]‐photocycloaddition reported by Stechl in 1963 [44], was the first photochemical reaction described for cyclopropenes. However, this reaction is unselective in most cases. Dürr [90, 91], De Boer and Breslow [43, 92] described the [2+2]‐photodimerization of 1,2‐diphenylcyclopropenes (Scheme 14A). Thus, sensitized irradiation of cyclopropene 81 led to the formation of the [2+2] photodimerization product 82 in good quantum yield. The reaction might take place via sensitization to reach a triplet state of the cyclopropene, which after a reaction with another cyclopropene at ground state generates a 1,4‐diradical intermediate with a favoured chair‐like conformation. A subsequent cyclization should account for the formation of tricycle 82. In contrast, cyclopropene 83 led to a mixture of two dimers, the expected [2+2]‐cycloadduct 84 and dimeric product 85. The formation of the latter product could be explained considering a boat‐like conformation, in which a bond‐rotation lead to a suitable geometry for a H‐transfer rather than a cyclization [43].

SCHEME 14.

Dimerization of cyclopropenes via sensitized [2+2] cycloaddition and side reactions.

Padwa and co‐workers also reported the photodimerization of 2‐(methoxycarbonyl)‐substituted cyclopropenes (Scheme 14B) [93, 94]. Interestingly, thioxanthone sensitized irradiation with UV light of cyclopropene 86 afforded the cyclohexadiene 87 arising from the ring‐opening of [2+2] dimer only as minor product, while the major product was dimer 88 showing a bicyclo[1.1.0]butane structure (Scheme 14B). The formation of this unanticipated dimer was explained considering the cyclopropyl radical ring‐opening of the postulated biradical intermediate and subsequent cyclization.

In 2025, Shen and co‐workers reported the photopromoted [2+2]‐cross‐dimerization of two cyclopropenes enabling the synthesis of nonsymmetric tricyclo[3.1.0.0^2,4]hexane derivatives (Scheme 14C) [95]. In particular, a chemoselective cross‐dimerization takes place among 3,3‐diaryl‐ and 3‐aryl‐3‐carboxyl‐substituted cyclopropenes 89 and 90, respectively, using visible light (450‐460 nm) in the presence of trifluoroacetylsilane 91 as sensitizer. Although the cross‐dimer tricycles 92 are the main products with good stereoselectivities, appreciable amounts of homo‐dimers were also observed. The authors proposed the participation of cyclopropene aggregates, either excimer or exciplet, since the triplet energy of the sensitizer is considerably lower than those calculated for any of the isolated cyclopropenes involved.

Importantly, the photopromoted [2+2] dimerization of cyclopropenes has found utility in the preparation of cross‐link polymers, as described by Reiser in 1982 (Scheme 14D) [96]. In particular, partial esterification of poly(vinyl alcohol) with 1,2‐diphenylcyclopropene‐3‐carboxylic acid to form 93, set the stage for light‐mediated linking via [2+2] dimerization to afford 94. The photo‐linking reaction occurred efficiently in the solid state in spite of the low concentration of reactive sites along the polymer structure.

The intermolecular [2+2] photocycloaddition of cyclopropenes and alkenes constitutes the most straightforward approach to the synthesis of housanes. In 1977, Arnold and co‐workers reported the first intermolecular selective cross [2+2] photocycloaddition (>350 nm, thioxanthone) of cyclopropene 5 with dimethyl fumarate (95) to afford housane 96 (Scheme 15A) [42, 97]. Subsequently, the analogous reactions with other electron‐deficient alkenes were performed [98]. It should be noticed that in these transformations, the triplet state of the cyclopropene was proposed to occur through a charge‐transfer complex. Subsequently, the groups of Famir [99] and Padwa [69, 100] independently reported the same reactivity with cyclopropenes bearing different substituents at the position 3, as well as 2‐carbomethoxy‐substituted cyclopropenes 86 (Scheme 15A) [100, 101, 102]. Much more recently, Davies, Knowles and co‐workers reported the synthesis of housanes 102 using tetrasubstituted cyclopropenes 100 and acrylates 101 (Scheme 15B) [103]. The photocycloaddition was accomplished under more convenient blue LED irradiation using an iridium complex ([Ir(dF(CF₃)ppy)₂(dtbbpy)][PF₆], Ir‐1) as sensitizer. Moreover, temperatures as low as –40°C are required to obtain good diastereoselectivities. In line with contemporary tendency, this work demonstrated that these type of reactions can also enjoy a remarkable scope. Since the starting cyclopropenes can be prepared in enantiopure form, enantioenriched housanes could also be prepared. Concurrently, Hari and co‐workers reported the intermolecular [2+2] photocycloaddition of 3,3‐disubstituted cyclopropenes 103 and maleimides 104 using visible light (440 nm) [104]. Remarkably, these transformation were performed using an organic sensitizer, such as 4CzlPN, which showed better efficiency that typical iridium complexes. This procedure stands also out for is remarkable scope and high diastereoselectivities.

SCHEME 15.

Sensitized [2+2]‐photocycloadditions of cyclopropenes and alkenes.

The intramolecular [2+2] photocycloaddition of cyclopropenes, such as 106 and 108, bearing a remote alkene group tethered at position 2 was reported by Padwa (Scheme 14C) [100, 101, 105]. In this case, tricyclic compounds 107 and 109 could be obtained by sensitized irradiation, yet the results were strongly dependent on the alkene substitution as well as the spatial requirements.

Apart from this canonical [2+2] photocycloadditions, intramolecular versions of this reaction with specifically substituted cyclopropenes have allowed the preparation of unconventional molecular architectures, which might be otherwise difficult to access. In 1977, Padwa and co‐workers described the photochemical reactivity of 3‐allyl cyclopropenes 39 and 41 (Scheme 16A) [69, 70]. Opposite to direct irradiation discussed above (see Scheme 9), sensitized irradiation of both cyclopropenes led to the formation of tricyclo[2.2.0.0^2,6]hexane derivative 110 as single product in an impressive 70% yield. Importantly, it was demonstrated that both cyclopropenes do not isomerize under photochemical conditions. The use of 3‐allyl‐substituted cyclopropenes 111 and 113, with a defined stereochemistry on the alkene, led to tricycles 112 and 114, respectively, suggesting a stereospecific process. The authors proposed a triplet sensitization to generate the expected 1,2‐diradical species, which undergoes a stepwise [2+2]‐cycloaddition via boat‐like intermediate [69, 70]. However, an “allowed” excited‐state [π2_s+π2_s] reaction was also considered by the authors.

SCHEME 16.

Synthesis of polycyclic scaffolds with unusual structures by intramolecular [2+2]‐photocycloadditions of cyclopropenes.

Padwa and co‐workers described the sensitized irradiation of 3‐(o‐vinylphenyl)‐substituted cyclopropene 115 (Scheme 16B) [106]. These substrates undergo an oddly easy [2+2]‐photocycloaddition to generate benzotricycle[3.2.0.0^2,7]heptane derivative 116 as single reaction product.

Padwa's group also reported the intramolecular [2+2] photocycloaddition of bis(cycloprop‐2‐enyl)methane derivative 117 (Scheme 16C) [107]. The sensitized irradiation (thioxanthone) of cyclopropene 117 led to the formation of bicyclo[2.2.1]heptane derivative 118. The reaction was proposed to occur via intramolecular [2+2] cycloaddition of the cyclopropenes to generate short‐lived quadricyclane intermediate, which undergo a rearrangement to the final product. Importantly, the direct irradiation leads to the same products, which should be then formed via singlet excited state.

2.7. Photoisomerization of 1‐Silylcyclopropenes

As stated above (see Scheme 2), the isomerization of cyclopropenes leading to the formation of allenes under irradiation is well‐known process [108], although the process is useless from a synthetic standpoint since mixtures containing 1,3‐dienes and alkynes are obtained and the product distribution strongly depends on the substitution pattern. In 1986, de Meijere and co‐workers described the isomerization of 1,2‐disubstituted cyclopropenes 119, bearing at least one silyl group, to allenes 120 as single reaction products under UV irradiation (Pyrex) in pentane (Scheme 17) [109]. Further reports by Kirms [110], and de Meijere [111], confirmed this selectivity trend. Interestingly, tetrakis(trimethylsilyl)cyclopropene (121) could be converted into the corresponding allene 122. The mechanism of this reaction is still unclear and after the light‐promoted excitation of cyclopropene, vinyl carbene or vinylidene intermediates might rearrange to the allene. It should be noticed that attempts to trap the vinyl carbene were unsuccessful, but theoretical calculations indicated that vinylidenes are higher in energy than the corresponding vinyl carbenes.

SCHEME 17.

Light‐mediated cyclopropene‐to‐allene rearrangement of 1‐silylcyclopropenes.

3. Photochemistry of Cyclopropenes With Other Light‐Excited Molecules

3.1. Light‐mediated Radical Additions to Cyclopropenes

The addition of radicals to alkenes constitutes one of the main reactivities of radical chemistry, with the classical tin‐mediated Giese reaction as the most emblematic transformation of this type. The impressive recent progress of photochemistry has permitted the expansion of this strategy in organic synthesis. On the one hand, photochemistry with visible light allow the generation of radicals under very mild reaction conditions. On the other hand, synthetically accessible and versatile radical precursors are now available.

In the context of cyclopropenes, radical additions have also been reported [112]. Regardless of the method employed for radical generation, the particular structure of cyclopropenes makes this reaction more complicated than for regular alkenes (Scheme 18). First, the radical addition to cyclopropenes is facilitated by the net loss of strain energy irrespective of the radical philicity. In 1‐substituted cyclopropenes, the regioselectivity of the radical addition is controlled by steric factors, generating the most substituted cyclopropyl radical intermediate. However, regioselectivity might be an issue when 1,2‐disubstituted cyclopropenes are involved. The substitution at position 3 dictates the stereochemistry of the addition, which takes place with trans selectivity with respect to the bulkier substituent. However, the cyclopropyl radical exhibits a pyramidal geometry, whose inversion of the configuration might proceed fast enough via planar p‐centered radical transition state. The complexity of the radical addition to cyclopropenes is aggravated by the possibility of cyclopropyl radicals to evolve through pathways involving ring opening reactions to allyl radicals.

SCHEME 18.

Mechanistic scenario for the radical addition to cyclopropenes.

The addition of radicals generated by irradiation to cyclopropenes was first reported by Saičić and co‐workers in 2000 using cyclopropenone ketal 123 and xanthates 124 as C‐centered radical precursors (Scheme 19A) [113]. Under irradiation, the addition of the α‐acyl radical generated from the xanthate led to the formation of a cyclopropyl radical, which readily recombined with the S‐centered radical to form xanthate derivatives 125. Compounds 125 were obtained in moderate yields and selectivities within a restricted scope, as depicted. Interestingly, the transformation proceeded solely under irradiation, with visible light irradiation (250 W xenophot sun‐lamp) providing better results than UV, while attempts using radical initiators such as peroxides or Et₃B failed.

SCHEME 19.

Light‐mediated addition of C‐centered radicals to cyclopropenes.

In 2017, Landais and co‐workers described the addition of radicals generated from α‐bromoacetophenones 127 to cyclopropenes 126 by irradiation with blue LED light in the presence of Ir‐2 (fac‐Ir(ppy)₃) as photocatalyst and K₂CO₃ as a base and subsequent mild heating in the dark at 60°C (Scheme 19B) [114]. In this manner, 1(4H)‐naphthalenones 128 bearing an all‐carbon benzylic quaternary stereocenter were obtained in moderate yields. Several examples, including remote functionalizations and heteroarenes, were shown demonstrating a reasonable scope. Moreover, complete transfer of chirality from an enantioenriched cyclopropene to the resulting naphthalenone derivative was also disclosed. The proposed mechanism started with a SET from the excited photocatalyst to generate an α‐phenacyl radical. Then, radical addition onto cyclopropene 126 would generate a highly reactive cyclopropyl radical, which underwent an intramolecular homolytic aromatic substitution to form a cyclohexadienyl radical intermediate. Next, oxidation to cyclohexadienyl cation served to return the photocatalyst to its initial oxidation state at the ground state and set the stage for the aromatization to unstable cyclopropane. Indeed, the final cyclopropane ring‐opening leading to compounds 128 is a base‐promoted reaction.

More recently, Sureshkumar and co‐workers described hydroacylation reactions of cyclopropenes by means of visible‐light irradiation (Scheme 19C) [115]. Irradiation at 456 nm in the presence of Ir‐3 ([Ir(ppy)₂dtbbpy][PF₆]) photocatalyst, α‐ketoacids 130 served as precursors of acyl radical intermediates, which were trapped by cyclopropenes 129 to afford 2‐acylcyclopropane derivatives 131. This transformation occurred with good yields and complete trans diastereoselectivities. The ample scope with respect to both cyclopropene and α‐ketoacid reagents is also remarkable. In this transformation, excitation of the photocatalyst and subsequent SET to α‐ketoacid serves to generate the acyl radical via decarboxylation. A regioselective radical addition to cyclopropene followed by a SET reduction to generate a cyclopropyl anion restoring the photocatalyst and final protonation leads to the resulting cyclopropane. Steric effects justify the observed trans diastereoselectivy.

In 2025, Cao, Han and co‐workers described the synthesis of deuterated cyclopropanes through a light‐mediated radical alkylation of cyclopropenes (Scheme 19D) [116]. In particular, 1‐aryl‐3,3‐dicarboxymethylcyclopropenes 132 were alkylated with methylamines 133 or glycinates 134 under irradiation with blue LED using 4CzlPN as photocatalyst in the presence of D₂O. A wide variety substituted cyclopropanes 135 were prepared in useful yields and reasonable diastereoselectivity. Moreover, the use of D₂O also enabled the efficient incorporation of deuterium in the final products. The alkyl radical is produced via SET of the excited photocatalyst and methylamine or radical decarboxylation of the glycinate. The radical addition takes place over an in‐situ deuterated cyclopropane leading to a cyclopropyl radical which is further reduced via SET to regenerate the photocatalyst and a final protonation with D₂O leads to cyclopropane 135.

The light‐mediated addition of radicals generated from sulfonates or sulfonyl chlorides to cyclopropenes has been recently studied by Sureshkumar and co‐workers (Scheme 20). First, they described the hydrosulfonylation of cyclopropenes 136 with sodium aryl sulfinates 137 using visible light (456 nm) and erythrosine‐B as the photocatalyst to prepare cyclopropyl sulfones 138 (Scheme 20A) [117]. The formation of sulfones 138 involves the photochemical generation of the sulfonyl radical and its subsequent addition to cyclopropene toward the cyclopropyl radical, which evolves through a reduction (SET) and protonation. By slight modification on the reaction conditions, the evolution of the generated cyclopropyl radical can be controlled. For instance, when the reaction was accomplished in the presence of NIS and a base, cyclopropenyl sulfones 139 were obtained (Scheme 20A) [118]. In this case, the cyclopropyl radical is trapped with iodo radical from NIS to form a iodosulfonylated cyclopropane intermediate. A concurrent SET reduced succinamide radical to the succinimide anion capable of promoting the elimination reaction to form 138. This sequence can be interrupted to obtain iodosulfonylated cyclopropanes 141 as reaction product (Scheme 20A) [119]. In this case, sulfonyl chlorides 140 in the presence of NaI were used and the reaction can be accomplished in water using a phase transfer catalysis. The formation of an EDA complex might be responsible for the generation of the sulfonyl radical under these conditions.

SCHEME 20.

Light‐mediated addition of S‐centered radicals to cyclopropenes.

Interestingly, the reaction outcome of the reaction of cyclopropenes 142 with secondary alkyl‐substituted sulfinates 143 could be controlled by employing different reaction conditions (Scheme 20B) [120]. The expected sulfonylcyclopropanes 144 were obtained by irradiation at 456 nm in the presence of Eosin‐Y as photocatalyst employing acetic acid as an additive in DMF at –10°C. On the contrary, the use of methanol at 40°C led to the formation of alkenes 145 through the addition of an alkyl radical generated by extrusion of SO₂ and a subsequent ring opening of the postulated cyclopropyl anion intermediate.

In the context of bioconjugation chemistry, Suero and co‐workers described the addition of S‐centered radicals to peptide‐cyclopropene conjugates 146 using (hetero)aromatic thiols 147 [121]. This process involves the use of an acridinium photocatalyst which is capable of generating the corresponding radical via light‐mediated SET processes, which undergo a regioselective addition to the cyclopropene‐decorated peptide to afford cyclopropanes 148 in remarkable yields (Scheme 21).

SCHEME 21.

Light‐mediated thiol‐ene coupling on peptide‐cyclopropene conjugates.

Other light‐mediated additions of radicals to cyclopropenes followed by ring‐opening of the cyclopropyl radical were recently described. In 2021, Waser and co‐workers reported the synthesis of quinolines 150 using 3‐aryl‐substituted cyclopropenes 149 and azidobenziodazolone (ABZ) as N‐centered azide radical precursor (Scheme 22A) [122, 123]. The reaction proceeded under irradiation with blue LED, but the use of acetoxybenziodoxole (BIOAc) and pyridine as additives was required to achieve acceptable yields. With respect to the scope, fully decorated quinolines substituted at the heterocyclic ring could be regioselectively obtained and the possibility to introduce the trifluoromethyl group was also demonstrated. The proposed mechanism starts with the excitation of ABZ to generate the azido radical. Control experiments suggest that BIOAc accelerates the process avoiding the degradation of ABZ, which slowly decomposes under irradiation. The azido radical undergoes addition to cyclopropene to form the corresponding cyclopropyl radical, which evolved via ring opening toward an α‐azidoallyl radical. After N₂ extrusion, a new iminil radical is generated and a cyclization involving the aryl substituent leading to a C‐centered tertiary radical. Finally, aromatization by oxidation with ABZ or other radial species and deprotonation facilitated by the presence of a base affords the quinoline 150.

SCHEME 22.

Light‐mediated addition of radicals to cyclopropenes involving ring‐opening reactions.

Later, Hu and co‐workers reported C‐centered radical additions to cyclopropenes with concomitant ring‐opening [124]. In this case, cyclopropenes 151 with diazo compounds 152 were irradiated with blue LED in the presence of I₂ and Ir‐3 as photocatalyst to afford 1,3‐diene derivatives 153 (Scheme 22B). The reaction took place with moderate to good yields but was restricted to cyclopropenes bearing one or two ester groups at the position 3 and arenes at the position 1. A plausible mechanism involves the in‐situ formation of a diiodo intermediate from the diazocompound, which serves as oxidant for the photo‐excited Ir(III)* to Ir(IV) and generates an α‐iodo alkyl radical and iodide. The alkyl radical adds to the cyclopropene to furnish a cyclopropyl radical, which undergoes an isomerization to the allyl radical. Finally, loss of iodine radical generates the diene. Further, a recombination of iodide and iodine radical serves to regenerate I₂ and the photocatalyst.

More recently, Li, Gao and co‐workers reported a visible‐light‐induced palladium‐catalyzed formal [3+3] cyclization of cyclopropenes with 2‐iodophenols (Scheme 22C) [125]. Thus, by means of blue LED irradiation in the presence of Pd(PPh₃)₄ as catalyst, ortho‐iodophenols 155 reacted with 3‐acyloxymethyl‐3‐arylcyclopropenes 154 to afford 2,2‐disubstituted 2H‐chromenes 156 in moderate to good yields, although the scope of the reaction is relatively limited. A plausible mechanism involve the direct excitation of Pd(0), which is capable of reducing the iodophenol to generate iodine and a Pd(I) aryl radical species via SET process. This species is proposed to exist in equilibrium with an aryl‐Pd(II) species. The aryl radical would add to the cyclopropenes forming a cyclopropyl radical, which would undergo a ring‐opening reaction to afford an allyl radical species. A radical recombination with Pd(I) might lead to an allyl‐Pd(II) intermediate. Then, the final C–O‐bond forming reaction should occur to provide the chromene derivative allowing catalytic turnover.

3.2. Light‐mediated Cycloaddition Reactions With Cyclopropenes at Ground State

Cyclopropenes are excellent substrates for cycloaddition reactions. The release of the strain energy is a powerful thermodynamic driving force and the reactions normally occur under very mild conditions. There are a few examples of cycloaddition reactions involving cyclopropenes at ground state with a photo‐excited reagent. In 2012, Christl and co‐workers described a double [3+2] photocycloaddition of cyclopropene (157) with chloranil (158) (Scheme 23A) [126]. By irradiation at low temperature using a medium‐pressure Hg‐lamp with adequate light filters (>400 nm) in benzene, which was replaced methanol upon consumption of 158, tetracyclic compound 159 was obtained as single reaction product in 36% yield. This result implied that two molecules of cyclopropene were incorporated to the product under photoexcitation, with one preserving the three‐membered ring. The proposed mechanism involves the photo‐excitation of chloranil (158) to its triplet to generate a diradical species to accomplish the first [3+2]‐cycloaddition. Another formal [3+2]‐cycloaddition with the second cyclopropene unit might lead to a tetracyclic intermediate. Subsequent ring expansion might give rise to a α‐chloroether intermediate, which in the presence of methanol finally led to acetal derivative 159.

SCHEME 23.

Light‐mediated [3+2]‐cycloaddition reactions involving.

Waser and co‐workers reported the synthesis of bicyclo[3.1.0]hexane derivatives 162 via a formal [3+2]‐cycloaddition cyclopropenes 160 with cyclopropylaniline derivatives 161 (Scheme 23B) [127]. Depending on the substrates, 4DPAIPN (2,4,5,6‐tetrakis(diphenylamino)isophthalonitrile) or Ir‐3 could be employed as photocatalysts operating under blue LED irradiation. A remarkable variety of bicyclic compounds 162 were obtained in good yields, but moderate diastereoselectivities. Moreover, the use of difluorocyclopropenes 163 was also reported enabling the preparation of the corresponding fluorinated bicyclic compounds 164 in acceptable yields and high diastereoselectivities. An oxidation of the cyclopropylamine 161 via light‐mediated SET to generate the corresponding cation radical and subsequent ring‐opening to iminium cation radical was proposed. Afterwards, the [3+2]‐cycloaddition with the cyclopropene 160 (or 163) affords the bicyclic derivatives 162 (or 164).

The [2+2]‐photocycloaddition of cyclopropenes with alkenes in which the cyclopropene partner remains in the ground state has been scarcely explore in comparison with the opposite excitation mode. In 1989, de Meijere and co‐workers described the [2+2]‐photocycloaddition of cyclic enones with 3,3‐dimethylcyclopropene, however the reaction is impractical due to the formation of several side products [128]. More recently, Vicente and co‐workers reported the intramolecular [2+2]‐photocycloaddition of 1,5‐cyclopropenenes 165 to prepare fused housanes 166 (Scheme 24A) [129]. The reaction could be accomplished using Ir‐1 or thioxanthone as sensitizers under blue or deep purple LED light irradiation, respectively. The reaction showed a respectable scope and mechanistic experiments supported the direct excitation of the alkene rather than the cyclopropene moiety.

SCHEME 24.

Light‐mediated [2+2]‐cycloaddition reactions involving cyclopropenes.

In addition to cycloaddition with alkenes, the analogous Paterno‐Büchi reaction of cyclopropenes with carbonyl compounds was recently reported by Hari and co‐workers during their studies of [2+2] photocycloadditions (Scheme 24B) [104]. Thus, they described the reaction of substituted cyclopropenes 167 with benzoquinone derivatives 168 using visible light (440 nm) in the absence of sensitizer to prepare 2‐oxabicyclo[2.1.0]pentane derivatives 169 in good yields and selectivity. This rare molecular architecture is accessible by excitation of the benzoquinone and a subsequent stepwise cyclization reaction with the cyclopropene.

3.3. Other Reactions

Initial studies on the oxidation of cyclopropenes promoted by light with photogenerated singlet oxygen were reported in the 1970's by Griffin and co‐workers (Scheme 25A) [130, 131]. For instance, 1,2,3‐triphenylcyclopropene (83) was converted into 1,3‐dicarbonyl compound 170 in 40% yield in the presence of oxygen and methylene blue as sensitizer via a dioxetane intermediate. However, these reactions are strongly influenced by the substitution and the mechanistic scenario is much more complex, as demonstrated later by Frimer and co‐workers using alkyl substituted cyclopropenes, which led normally to synthetically useless reaction mixtures [132, 133].

SCHEME 25.

Light‐mediated oxidations of cyclopropenes.

]In 2018, Xu and co‐workers reported the regioselective oxidative cleavage of cyclopropenyl carboxylates 171 under visible light irradiation (Scheme 25B) [134]. Using Ir‐1 photocatalyst with suitable redox properties in the presence of O₂ as oxidant, methylidene‐malonate derivatives 172 were obtained in moderate yields. Both aryl and esters groups were necessary to accomplish the reaction, since other substituents led to different oxidation processes. The authors proposed a mechanism initiated by light‐mediated SET process involving Ir‐1 and O₂. A subsequent reduction of the Ir(III) species generated a cyclopropyl radical cation. Nucleophilic attack of H₂O allowed a ring‐opening reaction step in which a loss of an electron and a proton also occurred. Final deprotonation afforded compounds 172. The use of H₂O¹⁸ confirmed that water was the source of the O‐atom in the final product.

Xiao and co‐workers reported in 2024 the desymmetrization‐addition of cyclopropenes to imines by synergistic photoredox and asymmetric cobalt catalysis (Scheme 26) [135]. Specifically, the reaction of 3,3‐disubstituted cyclopropenes 173 with imines 174 were converted into chiral functionalized cyclopropanes 175 in high yield, diastereo‐ and enantioselectivity with a remarkably wide scope. The reaction conditions involved the use of 4CzIPN as organic photocatalyst, CoI₂ and (S,S)Me‐DuPhos, a Hantzsch ester and i‐PrNEt₂ under blue LED irradiation. With this cocktail, light‐mediated SET events enable the generation of a L*Co(III)–H intermediate, which undergoes an enantioselective hydrometallation with the cyclopropene. A reduction to Co(II) followed by a subsequent addition to the imine led to final cyclopropanes 175.

SCHEME 26.

Light‐mediated cobalt‐catalyzed addition of cyclopropenes to imines.

Guo, Gao and co‐workers described the synthesis of cyclopropylphosphine oxides 178 by light‐mediated hydrophosphination of cyclopropenes 176 with diarylphosphine oxides 177 (Scheme 27) [136]. Thus, direct irradiation of these reagents with 390 nm light led to the diastereoselective formation of phosphine oxides in good yields, yet substitution in cyclopropene was restricted to arenes at the position 1 and esters at position 3. The proposed mechanism involved the formation of an EDA complex through H‐bonding, which set the stage for a light‐mediated SET process generating a charge transfer complex composed by a phosphine cation radical and cyclopropyl anion radical. Then, a proton transfer facilitated by the presence of water led to the corresponding neutral radicals that undergo a stereoselective coupling to form 178.

SCHEME 27.

Light‐mediated hydrophosphination of cyclopropenes with phosphine oxides.

4. Light‐mediated Bioorthogonal Chemistry Involving Cyclopropenes

Bioorthogonal chemistry has become an indispensable tool in biology and biomedicine for the understanding of chemical processes in living organisms. By definition, bioorthogonal transformations represent a class of high‐yielding chemical reactions between nonnative functional groups that proceed with fast kinetics and complete selective in biological environments without affecting biomolecules or interfering the biochemical processes. Among several organic compounds, cyclopropenes have emerged as promising exogenous tags fitting the requirements for bioorthogonal reactions [137]. On the one hand, cyclopropenes are smaller than other common functional groups, minimizing the impact on the 3D structure of the labelled protein and are excellent dienophiles capable of performing fast cycloadditions. In this context, cyclopropenes have also been used in light‐mediated bioorthogonal reactions, which are briefly discussed below.

In 2012, Lin and co‐workers reported the incorporation of 3,3‐disubstituted cyclopropenes as tags for protein labelling [138]. Based on the superior rates in a photo‐click reaction of lisyne‐derived cyclopropene 182 with tetrazole 180, the authors modified myoglobin (Myo) by attachment to ε‐amino group of a lysine residue and then fed to E. coli to become appended in the protein fourth position. The mutated protein Myo‐183 served for fluorescent labelling by photo‐click reaction with tetrazole 180 when irradiated at 302 nm for 1–12 min in a buffered solution (Scheme 28A). This procedure was applied to green fluorescent proteins (GFP) in mammalian cells (HEK293). While labelling was incomplete, showing some variability in the penetration of this photo‐click probe for this case, it provides opportunities for further improvement. Subsequently, the same group reported the synthesis and use of a stable and biocompatible spirocyclic cyclopropene which exhibited high reactivity toward tetrazoles in photoclick reactions [139]. In this case, a lysine residue was modified with a spiro[2.3]hex‐1‐ene cyclopropene 185 probe into a superfolder GFP protein (sfGFP) in BL21 cell lines (Scheme 28B). Kinetic studies performed in the cyclopropene‐labelled protein indicated that under irradiation at 302 nm, the light‐mediated reaction with tetrazole 187 in a buffered solution exhibited a fast kinetic, enabling a rapid (<10 s) bioorthogonal protein labelling.

SCHEME 28.

Photoclick reaction of cyclopropene‐tagged proteins with tetrazoles.

Taking advantage of the different reactivities between 1,3‐ and 3,3‐disubstituted cyclopropenes, Houk, Prescher and coworkers described the orthogonal reactions with bovine serum albumin (BSA) and lysozyme proteins tagged with cyclopropenes 189 and 190 (Scheme 29A) [140]. Thus, rhodamine‐tetrazine 193 react with 1,3‐disubstituted cyclopropene BSA‐191 via iEDDA (inverse electron demand Diels‐Alder), while no reaction was observed with cyclopropene BSA‐192. Subsequently, a photo‐click reaction of 3,3‐disubstituted cyclopropene BSA‐192 with tetrazole 194 took place under UV irradiation. However, it should be noticed that both cyclopropene‐tagged proteins could react with tetrazole 194 under irradiation and, therefore, the order of reaction is relevant for selectivity.

SCHEME 29.

Orthogonal iEDDA and photoclick reactions of 1,3‐ and 1,1‐disubstituted cyclopropene‐tagged biomolecules with tetrazines and tetrazoles.

The ability to control selectivity in bioorthogonal reactions by selection of the structure of the cyclopropene was further exploited by Wagenknecht and coworkers in the context of metabolic labelling of DNA (Scheme 29B) [141]. In particular, HeLa cells were incubated with cyclopropene‐modified deoxynucleoside 198 to label the DNA. Subsequent irradiation in the presence of a solution of tetrazole‐dye 200 at 405 nm induced the photoclick labelling, as demonstrated with the fluorescence observed. Again, by using 1,3‐ or 3,3‐disubstituted cyclopropenes, complementary bioorthogonal reaction could be selectively accomplished.

The possibility to control in time and space the iEDDA reaction using photoactivatable caged cyclopropenes was described by Jiang and co‐workers [142]. In particular, the authors employed substituted cyclopropenes decorated with a photolabile group, which are not able perform ligation with tetrazines. However, by exposure to light, cyclopropenes can be “turned‐on” and undergo the iEDDA reaction. The concept has been applied in a biological context using a tetrazine‐modified bovine serum albumin (BSA) and biotin‐conjugated Nvoc‐protected cyclopropene 203 (Scheme 30A) [143]. As expected, 203 was unreactive in the dark and did not afford any observable ligation with BSA‐tetrazine. On the contrary, exposure of 203 to light at 365 nm, led to a clear ligation to BSA‐tetrazine, demonstrating the in‐situ photochemical activation. Subsequently, the same group described a similar strategy on imaging tool to label membranes of fixed cultured cells (Scheme 30B) [144]. In this case, they used a cyclopropene 205 tagged with sulforhodamine B as fluorophore and Nvoc‐protected for a photochemical control of the activation. Moreover, the authors coupled the process with an oxidation activation of cathecol‐labelled phospholipid incorporated into cell membranes. Upon oxidation and irradiation with 365 nm light, a Diels‐Alder reaction with in‐situ generated ortho‐quinone was promoted and used for the first time as imaging tool.

SCHEME 30.

Photoactivatable cyclopropenes for Diels‐Alder reactions as imaging tools.

5. Summary and Outlook

Since the improvement of practical synthesis of cyclopropenes in the 1950s, a plethora of studies have demonstrated the amazingly rich and, often, distinctive reactivity of such small molecules. Most of the described reactivity of cyclopropenes deal with metal‐free addition or cycloaddition reactions as well as metal‐mediated or metal‐catalyzed transformations. With respect to photochemistry, fundamental studies were mostly performed during the 1970s and set the basis of the light‐mediated transformations of cyclopropenes. While these works mainly focused on mechanistic studies, they already pointed out that interesting synthetic applications might be feasible. However, those applications were not fully explored or established.

With the unstoppable growth of photochemistry in the past decade, it is surprising that cyclopropenes have not been merged with this trending topic in spite of the proved synthetic potential of cyclopropenes. Thus, only a few examples of photochemical reactions involving cyclopropenes, in comparison with other unsaturated compounds, have been reported in the last 15 years. Those studies have taken advantage of new photosensitizers capable of operating with less energetic visible light and, importantly, the synthetic utility of those transformations was demonstrated according to the contemporary standards regarding scope and applications. Moreover, the use of cyclopropenes in light‐mediated bioorthogonal chemistry highlights the usefulness of these compounds apart from organic chemistry.

In spite of these remarkable advances, considering novel available methodologies to prepare cyclopropenes decorated with substitution patterns previously inaccessible, it is foreseeable that novel transformations might be found, elevating the synthetic versatility of cyclopropenes. Additionally, the possibility to generate reactive intermediates by irradiation under mild conditions, which are not compromising the stability of cyclopropenes, might serve to explore reactions in which cyclopropenes are participating at their ground state.

We hope that this review might serve as a stimulus for further studies toward the discovery of new light‐mediated reactions of cyclopropenes, which might find applications in different research areas.

Conflicts of Interest

The authors declare no conflict of interest.

Biographies

David Suárez‐García (Oviedo, Spain) obtained his BSc (2022) and MSc (2023) in Chemistry at Universidad de Oviedo. He is currently pursuing his PhD studies under the supervision of Dr. R. Vicente working on the development of synthetic methodologies using cyclopropenes by means of photochemistry and transition‐metal catalysis.

Darío Coto (Langreo, Spain) obtained his BSc (2020) and MSc (2021) in Chemistry at Universidad de Oviedo. In 2025, he obtained is PhD under the supervision of Dr. R. Vicente working in the synthetic uses of cyclopropenes as carbene precursors.

Rubén Vicente (Guadalajara, Spain) obtained his BSc in Chemistry at Universidad Complutense (Madrid, Spain) in 2000 and his PhD at Universidad de Oviedo (Spain) in 2006 under the supervision of Prof. J. Barluenga. After a postdoctoral stay with Prof. L. Ackermann at the Georg‐August‐Universität Göttingen (Germany), he returned to Oviedo in 2010 as Research Associate (“Ramon y Cajal” fellow). He was promoted to Assistant Professor (tenured, 2017) and, subsequently, to Associate Professor (2019) at the Universidad de Oviedo. He received the Spanish Royal Chemical Society Sigma‐Aldrich (2014) and Lilly (2017) awards for young researchers. His research focuses on synthetic methodologies using metal catalysis with emphasis on strained molecules.

To the memory of our colleague Prof. Iván Lavandera

Suárez‐García D., Coto D., and Vicente R., “Cyclopropenes in Photochemical Reactions.” Chemistry – A European Journal 32, no. 3 (2026): e03281. 10.1002/chem.202503281