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Visible‐light‐mediated [2+2] photocycloaddition reaction can be considered an ideal solution due to its green and sustainable properties, and is one of the most efficient methods to synthesize four‐membered ring motifs. Although research on the [2+2] photocycloaddition of alkynes is challenging because of the diminished reactivity of alkynes, and the more significant ring strain of the products, remarkable achievements have been made in this field. In this article, we highlight the recent advances in visible‐light‐mediated [2+2] photocycloaddition reactions of alkynes, with focus on the reaction mechanism and the late‐stage synthetic applications. Advances in obtaining cyclobutenes, azetines, and oxetene active intermediates continue to be breakthroughs in this fascinating field of research. [ABSTRACT FROM AUTHOR]

Five novel styrylnaphthyridine derivatives were synthesized and shown to operate as photoswitchable, selective ligands for abasic site‐containing DNA (AP‐DNA), which is an important therapeutic and diagnostic target. These compounds associate with AP‐DNA with binding constants of 0.5–8.4×104 M−1 as shown by photometric and fluorimetric titrations. Specifically, these ligands bind preferentially to AP‐DNA relative to regularly paired duplex DNA. As a special feature, the association of these ligands with DNA can be controlled by means of a reversible [2+2] photocycloaddition. Upon irradiation at 420 nm the photodimer is formed, which does not bind to AP‐DNA. In turn, the naphthyridine is regained with excitation at 315 nm. Most notably, this photoinduced deactivation and release of the DNA ligand can be performed in situ in the presence of AP‐DNA, thus providing a tool for on‐demand delivery of a DNA binder. Overall, these results provide a promising starting point for the development of functional AP‐DNA ligands whose bioactivity can be modulated by light with local and temporal control. [ABSTRACT FROM AUTHOR]

We propose a mechanism for substituent‐responsive reactivities of p‐quinodimethane derivatives with four ester groups through their hierarchical and asymmetric assembly modes. Four asymmetric 7,8,8‐tris(methoxycarbonyl)‐p‐quinodimethanes with a 7‐positioned ethoxycarbonyl (2 a(H)), 2'‐fluoroethoxycarbonyl (2 b(F)), 2'‐chloroethoxycarbonyl (2 c(Cl)), or 2'‐bromoethoxycarbonyl (2 d(Br)) were synthesized and crystallized. 2 a(H), 2 b(F) and 2 d(Br) afforded only one shape crystal, while 2 c(Cl) did two polymorphic 2 c(Cl)‐α and 2 c(Cl)‐β. UV‐irradiation induced topochemical polymerization for 2 a(H), no reactions for 2 b(F) and 2 c(Cl)‐α, and [6+6] photocycloaddition dimerization for 2 c(Cl)‐β and 2 d(Br). Such substituent‐responsive reactivities and crystal structures were compared with those of the known symmetric 7,7,8,8‐tetrakis(alkoxycarbonyl)‐p‐quinodimethanes such as 7,7,8,8‐tetrakis(methoxycarbonyl)‐ (1 a(Me)‐α and 1 a(Me)‐β), 7,7,8,8‐tetrakis(ethoxycarbonyl)‐ (1 b(Et)), and 7,7,8,8‐tetrakis(bromoethoxycarbonyl)‐ (1 c(BrEt)). The comparative study clarified that the reactivities and crystal structures are classified into four types that link to each other. This linkage is understandable when we analyze the crystal structures through the following hierarchical and asymmetric assemblies; conformers, dimers, one dimensional (1D)‐columns, two dimensional (2D)‐sheets, and three dimensional (3D)‐stacked sheets (3D‐crystals). This supramolecular viewpoint is supported by intermolecular interaction energies among neighbored molecules with the density functional theory (DFT) calculation. Such research enables us to elucidate the substituent‐responsive reactivities of the crystals, and reminds us of the selection of the right path in a so‐called "maze game". [ABSTRACT FROM AUTHOR]

Two representative organic photoreactions, namely a bimolecular photocycloaddition and a monomolecular photorearrangement, are presented that are accelerated when the reaction is performed "on‐water", that is, at the water‐substrate interface with no solvation of the reaction components. According to the established models of ground‐state reactions "on‐water", the enhanced efficiency of the photoreactions is explained by hydrophobic effects (Paternó‐Büchi reaction) or specific hydrogen bonding (di‐π‐methane rearrangement) at the water‐substrate interface that decrease the energy of the respective transition state. These results point to the potential of this approach to conduct photoreactions more efficiently in an ecologically favorable medium. [ABSTRACT FROM AUTHOR]

N‐Alkyl‐N‐(2‐(1‐arylvinyl)aryl)cinnamamides are converted into natural product inspired scaffolds via iridium photocatalyzed intramolecular [2+2] photocycloaddition. The protocol has a broad substrate scope, whilst operating under mild reaction conditions. Tethering four components forming a trisubstituted cyclobutane core builds rapidly high molecular complexity. Our approach allows the design and synthesis of a variety of tetrahydrocyclobuta[c]quinolin‐3(1H)‐ones, in yields ranging between 20–99 %, and with excellent regio‐ and diastereoselectivity. Moreover, it was demonstrated that the intramolecular [2+2]‐cycloaddition of 1,7‐enynes—after fragmentation of the cyclobutane ring—leads to enyne‐metathesis‐like products. [ABSTRACT FROM AUTHOR]

Polyimidazolium‐based cages are considered promising materials based on their fascinating properties and potential applications. These three‐dimensional functional structures are highly desirable for the recognition of particular guest molecules, however, their synthesis remains challenging. In this work, we have designed and synthesizes a pure [n]‐imidazolium (n=16) cage, the hexadecakisimidazolium salt H16‐2(PF6)16, from tetragonal octakisimidazolium salt H8‐1(PF6)8. The synthetic method involves formation of metal‐carbene templates, a quadruple photochemical [2+2] cycloaddition reaction and subsequent removal of metal ions. Specifically, the synthesized cage, featuring sixteen imidazolium moieties, demonstrated high efficiency for the selective fluorescent recognition of 8‐hydroxy‐1,3,6‐pyrene trisulfonate (HPTS). The present work not only further develops the metal‐carbene template strategy by exploiting a new type of polyimidazolium cage, but also provides encouraging prospects for the design of versatile imidazolium‐based functional acceptors. [ABSTRACT FROM AUTHOR]

A chiral phosphoric acid with a 2,2'‐binaphthol core was prepared that displays two thioxanthone moieties at the 3,3'‐position as light‐harvesting antennas. Despite its relatively low triplet energy, the phosphoric acid was found to be an efficient catalyst for the enantioselective intermolecular [2+2] photocycloaddition of β‐carboxyl‐substituted cyclic enones (e.r. up to 93:7). Binding of the carboxylic acid to the sensitizer is suggested by NMR studies and by DFT calculations to occur by means of two hydrogen bonds. The binding event not only enables an enantioface differentiation but also modulates the triplet energy of the substrates. [ABSTRACT FROM AUTHOR]

Sydnone‐based cycloaddition reactions are a versatile platform for pyrazole synthesis, however they operate under harsh conditions (high temperature and long reaction times). Herein we report a strategy that addresses this limitation utilizing the synergistic combination of organocatalysis and visible‐light photocatalysis. This new approach proceeds under ambient conditions and with excellent levels of regiocontrol. Mechanistic studies suggest that photoactivation of sydnones, rather than enamines, is key to the successful implementation of this process. [ABSTRACT FROM AUTHOR]

The intramolecular [2+2] photocycloaddition of 3‐alkenyl‐2‐cycloalkenones was performed in an enantioselective fashion (nine representative examples, 54–86 % yield, 76–96 % ee) upon irradiation at λ=366 nm in the presence of an AlBr3‐activated oxazaborolidine as the Lewis acid. An extensive screening of proline‐derived oxazaborolidines showed that the enantioface differentiation depends strongly on the nature of the aryl group at the 3‐position of the heterocycle. DFT calculations of the Lewis acid–substrate complex indicate that attractive dispersion forces may be responsible for a change of the binding mode. The catalytic [2+2] photocycloaddition was shown to proceed on the triplet hypersurface with a quantum yield of 0.05. The positive effect of Lewis acids on the outcome of a given intramolecular [2+2] photocycloaddition was illustrated by optimizing the key step in a concise total synthesis of the sesquiterpene (±)‐italicene. [ABSTRACT FROM AUTHOR]

[2+2] Photocycloaddition of two olefins is a general method to assemble the core scaffold, cyclobutane, found in numerous bioactive molecules. A new approach to synthesize cyclobutanes through multicomponent cascade reactions by merging aldol reaction and Witting reaction with visible‐light‐induced [2+2] cycloaddition is reported. An array of cyclobutanes with high selectivity has been achieved from commercially available aldehydes, ketones (or phosphorus ylide), and olefins with visible‐light irradiation of a catalytic amount of (fac‐tris(2‐phenylpyridinato‐C2,N)iridium) ([Ir(ppy)3]) at room temperature. Control experiments and spectroscopic studies revealed that the triplet–triplet energy transfer from the excited [Ir(ppy)3]* to enones, generated in situ from aldehyde and ketone or aldehyde and phosphorus ylide, is responsible for these simple and efficient muticomponent transformations. Synthesis of cyclobutanes through multicomponent cascade reactions is described. An array of cyclobutanes with high selectivity has been achieved from commercially available aldehydes, ketones, or phosphorus ylide, olefins with visible‐light irradiation of a catalytic amount of [Ir(ppy)3] at room temperature. [ABSTRACT FROM AUTHOR]

A 2‐alkenoylpyridine‐bound N,N′‐dioxide–TbIII complex has been found to absorb visible light to reach the excited state, leading to the direct visible‐light‐excited catalytic enantioselective [2+2] cycloaddition of 2‐alkenoylpyridines to various alkenes in the absence of an additional photosensitizer. Diverse enantioenriched cyclobutanes were successfully obtained (yields up to 70 %, >19:1 d.r. 92 % ee). The new chiral terbium(III) complex features a bathochromic shift, lower excitation energy, and facile intersystem crossing due to paramagnetic and heavy‐atom effects, which enable the antenna 2‐alkenoylpyridines to be excited. For comparison, a chiral N,N′‐dioxide–ScIII complex in combination with [Ru(bpy)3]Cl2 was efficient in the enantioselective photocycloaddition reactions of 2′‐hydroxychalcones with alkenes, thereby revealing that both substrates and metal salts have significant effects on the reaction. Exciting terbium complex: The terbium complex of a novel four‐carbon‐linked L4‐RaPr2 ligand efficiently promotes the visible‐light‐excited [2+2] cycloaddition reactions of 2‐alkenoylpyridines with diverse alkenes to produce diverse enantioenriched cyclobutanes (see scheme). A plausible mechanism for the photocycloaddition reaction is discussed. [ABSTRACT FROM AUTHOR]

Abstract: In searching for practical crystalline porous solids, two unique hybrid materials with featured functions, In‐bpy and In‐dpe, were prepared without deliberately designed organic linker units or complex post‐modification procedures. Composed of oxalate‐embedded metal phosphite (MPO) sheets and bipyridyl‐type ligands of varied molecular lengths, they show a common pillar‐layered topology but are the first well‐characterized organo‐MPOs to possess genuine porosity, substantiated by CO2 adsorption, and structural stability under harsh conditions. In‐bpy exhibits a turn‐on fluorescence signal when in contact with p‐xylene, making it the first MPO‐based sensing material with selectivity and recyclability. Furthermore, In‐dpe demonstrates a facile and unprecedented route to the superhydrophobicity of porous solids via a [2+2] photocycloaddition reaction between linker and foreign units. Our findings suggest that MPO may serve as a promising platform for hybrid frameworks to create many more functional porous materials. [ABSTRACT FROM AUTHOR]

Synthesis of aza-rocaglates, nitrogen-containing analogues of the rocaglate natural products, is reported. The route features ESIPT-mediated (3+2) photocycloaddition of 1-alkyl-2-aryl-3-hydroxyquinolinones with the dipolarophile methyl cinnamate. A continuous photoflow reactor was utilized for photocycloadditions. An array of compounds bearing the hexahydrocyclopenta[ b]indole core structure was synthesized and evaluated in translation inhibition assays. [ABSTRACT FROM AUTHOR]

Reversible photo-cross-linking of a DNA duplex through the [2+2] photocycloaddition of styrylpyrene is reported. Styrylpyrene moieties on d-threoninol linkers were introduced into complementary positions on DNA strands. Irradiation of the styrylpyrene pair in the duplex with visible light at λ=455 nm induced a [2+2] photocycloaddition between styrylpyrenes that cross-linked the two strands of the duplex. Two diastereomers were formed after [2+2] photocycloaddition as a result of rotation of the styrylpyrene residues. Also, the cycloreversion reaction was induced by UV light at λ=340 nm, which reversibly yielded the uncross-linked strands. [ABSTRACT FROM AUTHOR]

An enantioselective synthesis of an intermediate in the Tanino total synthesis of solanoeclepin A has been developed. The key step was an intramolecular [2+2] photocycloaddition, which led to the tricyclo[5.2.1.01, 6]decane core in six steps. The first photosubstrate, prepared through an indium-mediated Barbier-type reaction, gave an excellent [2+2] cycloaddition, but it could not be obtained in sufficient enantiopurity. The second photosubstrate, prepared through an asymmetric allene diborylation in high enantiomeric excess, gave the [2+2] cycloaddition product in high yield on irradiation at 365 nm on 20 g scale in a flow system. Other important steps were the replacement of a boronate group at the quaternary carbon by a vinyl group and diastereoselective cyclopropanation of an allylic alcohol. [ABSTRACT FROM AUTHOR]

The stereoselective synthesis of e-isomers of dimethyl esters of 1,3-diaminotruxillic acid in three steps is reported. The first step is the ortho-palladation of (Z)-2-aryl-4- aryliden-5(4H)-oxazolones 1 to give dinuclear complexes 2 with bridging carboxylates. The reaction occurs through regioselective activation of the ortho-C—H bond of the 4-arylidene ring in carboxylic acids. The second step is the [2+2]- photocycloaddition of the C=C exocyclic bonds of the oxazolone skeleton in 2 to afford the corresponding dinuclear ortho-palladated cyclobutanes 3. This key step was performed very efficiently by using LED light sources with different wavelengths (465, 525 or 625 nm) in flow microreactors. The final step involved the depalladation of 3 by hydrogenation in methanol to afford the e-1,3-diaminotruxillic acid derivatives as single isomers. [ABSTRACT FROM AUTHOR]

A strategy for the enantioselective [2+2] photocycloaddition of isoquinolones with alkenes is presented, in which the formation of a supramolecular complex between a chiral template and the substrate ensures high enantioface differentiation by shielding one face of the substrate. Fifteen different electron-deficient alkenes and ten different substituted isoquinolones undergo efficient photocycloaddition, yielding the cyclobutane products in excellent yields and with outstanding regio-, diastereo- and enantioselectivities (up to 99 % ee). The mechanism of the reaction is investigated by means of triplet sensitization/quenching and radical clock experiments, the results of which are consistent with the involvement of a triplet excited state and a 1,4-biradical intermediate. The variety of functionalized cyclobutanes obtained using this approach can be further increased by straightforward synthetic transformations of the photoadducts, allowing rapid access to libraries of compounds for various applications. [ABSTRACT FROM AUTHOR]

Tricks of the trade: Because intramolecular Cu‐catalyzed access to bicyclo[4.2.0]octanes is not feasible, an oxygen bridge was introduced to facilitate the [2+2] photocycloaddition. Starting from compounds similar to 1, products such as 2 could be obtained enantioselectiviely in three steps after ring‐opening metathesis (see scheme). [ABSTRACT FROM AUTHOR]