Cycloaddition Retroelectrocyclization Research Articles

Yb(OTf)<sub>3</sub>‐Catalyzed C=C Bond Cleavage‐Reassembly Enabling Bicyclization: Regioselective Synthesis of Heteroarylated Pentacyclic Indoles

A Yb(OTf)<sub>3</sub>‐catalyzed [2 + 2] cycloaddition /retro‐electrocyclization (CA‐RE)/ bicyclization of 1‐(2‐aminoarylaklynyl)‐naphthalen‐2‐ols and 3‐ylideneoxindoles is reported, enabling a direct C=C bond cleavage‐reassembly process to regioselectively synthesize a variety of quinoline‐tethered benzo[5,6]chromeno[2,3‐b]indoles in 31‐84% yields. Exchanging the amino group for the hydroxyl group in the arylalkynyl unit of the naphthalen‐2‐ol substrate resulted in chromenyl chromeno[2,3‐b]indoles via a similar cascade process.

Easy but Efficient: Facile Approach to Molecule with Theoretically Justified Donor-Acceptor Structure for Effective Photothermal Conversion and Intravenous Photothermal Therapy.

To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2W cm-2). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.

Perspectives on push-pull chromophores derived from click-type [2 + 2] cycloaddition-retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes.

Various push-pull chromophores can be synthesized in a single and atom-economical step through [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) reactions involving diverse electron-rich alkynes and electron-deficient alkenes. In this review, a comprehensive investigation of the recent and noteworthy advancements in the research on push-pull chromophores prepared via the [2 + 2] CA-RE reaction is conducted. In particular, an overview of the physicochemical properties of the family of these compounds that have been investigated is provided to clarify their potential for future applications.

Cycloaddition - Retro-Electrocyclization Click Reaction of Amine End-Capped Oligoynes with Tetracyanoethylene.

Here we show the first example of cycloaddition - retro-electrocyclization (CA-RE) click reaction involving nitrogen end-capped push-pull oligoynes. The reported CA-RE reaction with TCNE (tetracyanoethylene) is fully regioselective and leads exclusively to the unprecedented TCBD (tetracyanobuta-1,3-diene-2,3-diyl) end-capped carbon rods. The molecular structure of products was unambiguously confirmed using X-ray single crystal diffraction and their optical and electronic properties of were investigated experimentally and rationalized using DFT (density functional theory) calculations.

A Mechanistic Study about the Formation of Tetracyanobutadienes Revealed an Autocatalytic Behavior

AbstractIn a recent paper in Chemistry – A European Journal, Nielsen and coworkers reported a deep study on the mechanism of the [2+2] cycloaddition‐retroelectrocyclization (CA‐RE) between an electron‐rich alkyne and tetracyanoethylene (TCNE), inducing the formation of a 1,1,4,4‐tetracyanobutadiene (TCBD). Following a robust kinetic study, the authors confirmed important intermediates and determined this reaction to be autocatalytic for the first time. Given the increasing use of TCBDs in the community and the strength of the CA‐RE reaction this paper offers important insights for future developments of this promising reaction.

Tetracyanobuta-1,3-diene (TCBD)-appended pyrrolopyrrole aza-BODIPYs as a panchromatic chromophore based on the push-pull strategy

Pyrrolopyrrole aza-BODIPY (PPAB), a dimeric BODIPY analogue containing a pyrrolopyrrole structure at the center, exhibits intense far-red and near-infrared (NIR) absorption and emission. Herein, tetracyanobuta-1,3-diene-appended PPABs (TCBD-PPABs) were synthesized by post-modification based on a [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction with tetracyanoethylene. Owing to the redshift of the PPAB absorption in the NIR region and the emergence of the intramolecular charge-transfer band in the visible region, TCBD-PPABs exhibit panchromatic absorption in the visible/NIR regions.

Clicking together Alkynes and Tetracyanoethylene.

The [2+2] cycloaddition - retro-electrocyclization (CA-RE) reaction allows ready synthesis of redox-active donor-acceptor chromophores from an electron-rich alkyne and electron-poor olefins like tetracyanoethylene (TCNE). The detailed mechanism of the reaction has been subject of both computational and experimental studies. While several studies point towards a stepwise mechanism via a zwitterionic intermediate for the first step, the cycloaddition, the reaction follows neither simple second-order nor first-order kinetics. Recent studies have shown that the kinetics can be understood if an autocatalytic step is introduced in the mechanism, in which complex formation with the donor-substituted tetracyanobutadiene (TCBD) product possibly facilitates nucleophilic attack of the alkyne onto TCNE, generating the zwitterionic intermediate of the CA step. This Concept highlights the convenient use of the "click-like" CA-RE reaction to obtain elaborate donor-acceptor chromophores and the recent mechanistic results.

Minimalist Design for Solar Energy Conversion: Revamping the π-Grid of an Organic Framework into Open-Shell Superabsorbers.

We apply a versatile reaction to a versatile solid: the former involves the electron-deficient alkene tetracyanoethylene (TCNE) as the guest reactant; the latter consists of stacked 2D honeycomb covalent networks based on the electron-rich β-ketoenamine hinges that also activate the conjugated, connecting alkyne units. The TCNE/alkyne reaction is a [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) that forms strong push-pull units directly into the backbone of the framework-i.e., using only the minimalist "bare-bones" scaffold, without the need for additional side groups of alkynes or other functions. The ability of the stacked alkyne units (i.e., as part of the honeycomb mass) to undergo such extensive rearrangement highlights the structural flexibility of these covalent organic framework (COF) hosts. The COF solids remain porous, crystalline, and air-/water-stable after the CA-RE modification, while the resulting push-pull units feature distinct open-shell/free-radical character, are strongly light-absorbing, and shift the absorption ends from 590 nm to around 1900 nm (band gaps from 2.17-2.23 to 0.87-0.95 eV), so as to better capture sunlight (especially the infrared region which takes up 52% of the solar energy). As a result, the modified COF materials achieve the highest photothermal conversion performances, holding promise in thermoelectric power generation and solar steam generation (e.g., with solar-vapor conversion efficiencies >96%).

Accelerated Intramolecular Charge Transfer in Tetracyanobutadiene- and Expanded Tetracyanobutadiene-Incorporated Asymmetric Triphenylamine–Quinoxaline Push–Pull Conjugates

The excited-state properties of an asymmetric triphenylamine–quinoxaline push–pull system wherein triphenylamine and quinoxaline take up the roles of an electron donor and acceptor, respectively, are initially investigated. Further, in order to improve the push–pull effect, powerful electron acceptors, viz., 1,1,4,4-tetracyanobutadiene (TCBD) and cyclohexa-2,5-diene-1,4-diylidene-expanded tetracyanobutadiene (also known as expanded-TCBD or exTCBD), have been introduced into the triphenylamine–quinoxaline molecular framework using a catalyst-free [2 + 2] cycloaddition–retroelectrocyclization reaction. The presence of these electron acceptors caused strong ground-state polarization extending the absorption well into the near-IR region accompanied by strong fluorescence quenching due to intramolecular charge transfer (CT). Systematic studies were performed using a suite of spectral, electrochemical, computational, and pump–probe spectroscopic techniques to unravel the intramolecular CT mechanism and to probe the role of TCBD and exTCBD in promoting excited-state CT and separation events. Faster CT in exTCBD-derived compared to that in TCBD-derived push–pull systems has been witnessed in polar benzonitrile.

Synthesis and Characterization of Tetraphenylethene AIEgen-Based Push-Pull Chromophores for Photothermal Applications: Could the Cycloaddition-Retroelectrocyclization Click Reaction Make Any Molecule Photothermally Active?

Three new tetraphenylethene (TPE) push-pull chromophores exhibiting strong intramolecular charge transfer (ICT) are described. They were obtained via [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) click reactions on an electron-rich alkyne-tetrafunctionalized TPE (TPE-alkyne) using both 1,1,2,2-tetracyanoethene (TCNE), 7,7,8,8-tetracyanoquinodimethane (TCNQ) and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) as electron-deficient alkenes. Only the starting TPE-alkyne displayed significant AIE behavior, whereas for TPE-TCNE, a faint effect was observed, and for TPE-TCNQ and TPE-F4-TCNQ, no fluorescence was observed in any conditions. The main ICT bands that dominate the UV-Visible absorption spectra underwent a pronounced red-shift beyond the near-infrared (NIR) region for TPE-F4-TCNQ. Based on TD-DFT calculations, it was shown that the ICT character shown by the compounds exclusively originated from the clicked moieties independently of the nature of the central molecular platform. Photothermal (PT) studies conducted on both TPE-TCNQ and TPE-F4-TCNQ in the solid state revealed excellent properties, especially for TPE-F4-TCNQ. These results indicated that CA-RE reaction of TCNQ or F4-TCNQ with donor-substituted are promising candidates for PT applications.

A study of [2 + 2] cycloaddition-retroelectrocyclization in water: observation of substrate-driven transient-nanoreactor-induced new reactivity.

Organic solvents limit [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) in biological fields. We examined the formation of 1,1,4,4-tetracyanobuta-1,3-dienes (TCBDs) through CA-RE reactions and their unusual reactivity to produce N-heterocyclic compounds when the nature of the surfactant and the concentrations were varied in the aqueous phase. An environment in which transient self-assemblies (vesicles) were induced by the substrate and surfactant molecules initiated new reactivity through H2O addition on the TCBD, generating the enol form of the intermediate, which results in the formation of the 6,6-dicyano-heteropentafulvene (amidofulvene) compound, while lamellar sheets at higher concentrations favored TCBD generation. Interestingly, the amidofulvene underwent a clean transformation to 6-membered heterocycles that resemble cardiotonic drugs (milrinone, amrinone) via keto-enol tautomerism mediated by a polar aprotic solvent, opening up a new avenue for drug discovery. Unlike organic-solvent-mediated CA-RE reactions, the present nanoreactor-mediated approach enabled the selective production of TCBDs as well as new heterocycles using H2O as a green solvent. In addition to the widely explored organic electronics/materials, we believe that this study will help to overcome the long-standing limitation of CA-RE reaction applicability in biological fields.

On the Mechanism of the Formal [2+2] Cycloaddition - Retro-electrocyclization (CA-RE) Reaction.

The [2+2] cycloaddition - retro-electrocyclization (CA-RE) reaction is a "click-like" protocol for facile synthesis of donor-acceptor chromophores from an alkyne and tetracyanoethylene. Herein we shed light on the mechanism of this reaction by detailed kinetics studies using 1 H NMR spectroscopy. By considering several experiments simultaneously, a variety of mechanistic models was evaluated. Surprisingly, a model in which the final 1,1,4,4-tetracyanobuta-1,3-diene product promoted the first step was the only one that described well the experimental data. This autocatalysis model also involved a non-concerted, stepwise formation of the cyclobutene cycloaddition adduct. By proper choice of conditions, we were able to generate the transient cyclobutene in sufficient amount to verify it as an intermediate using 13 C NMR spectroscopy. For its final retro-electrocyclization step, simple first-order kinetics was observed and only minor solvent dependence, which indicates a concerted reaction.

Tetracyanobutadiene Bridged Push-Pull Chromophores: Development of New Generation Optoelectronic Materials.

This review describes the design strategies used for the synthesis of various tetracyanobutadiene bridged donor-acceptor molecular architectures by a click type [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction sequence. The photophysical and electrochemical properties of the tetracyanobutadiene bridged molecular architectures based on various moieties including diketopyrrolopyrrole, isoindigo, benzothiadiazole, pyrene, pyrazabole, truxene, boron dipyrromethene (BODIPY), phenothiazine, triphenylamine, thiazole and bisthiazole are summarized. Further, we discuss some important applications of the tetracyanobutadiene bridged derivatives in dye sensitized solar cells, bulk heterojunction solar cells and photothermal cancer therapy.

3-Alkynylindoles as Building Blocks for the Synthesis of Electronically Tunable Indole-Based Push-Pull Chromophores.

In this study, two different classes of push–pull chromophores were synthesized in modest to excellent yields by formal [2+2] cycloaddition-retroelectrocyclization (CA-RE) reactions. N-Methyl indole was introduced as a new donor group to activate alkynes in the CA-RE transformations. Depending on the side groups’ size and donor/acceptor characteristics, N-methyl indole-containing compounds exhibited λmax values ranging between 378 and 658 nm. The optoelectronic properties of the reported D–A-type structures were studied by UV/vis spectroscopy and computational studies. The complete regioselectivity observed in the products was elaborated by one-dimensional (1D) and two-dimensional (2D) NMR studies, and the electron donor strength order of N-alkyl indole and triazene donor groups was also established. The intramolecular charge-transfer characteristics of the target push–pull chromophores were investigated by frontier orbital depictions, electrostatic potential maps, and time-dependent density functional theory calculations. Overall, the computational and experimental results match each other. Integrating a new donor group, N-alkyl indole, into the substrates used in formal [2+2] cycloaddition-retroelectrocyclizations has significant potential to overcome the limited donor-substituted substrate scope problem of CA-RE reactions.

Synthesis, Structure, and Significant Energy Gap Modulation of Symmetrical Silafluorene-Cored Tetracyanobutadiene and Tetracyanoquinodimethane Derivatives.

A series of symmetrical tetracyanobutadiene and tetracyanoquinodimethane derivatives with a D-A-D'-A-D structural configuration and silafluorene core (D') were designed and readily synthesized via a [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction. We found that the photophysical properties and HOMO and LUMO energy levels and gaps of the silafluorene derivatives could be profoundly remolded through CA-RE reactions and modulated by varying the peripheral donor units from phenyl, m-dimethoxyphenyl, and N,N-dimethylaniline to triphenylamine groups. After CA-RE reactions, the HOMO-LUMO gaps of 1a-1j are in the range of 1.75-2.78 eV, with significant decreases of 0.52-1.46 eV compared to those of the parent silafluorene compounds 2a-2j. The intriguing crystal structures of 1f and 1j were analyzed and elucidated to show their unique potential porosity. The stability, electrochemical, and computational studies were systematically performed to unveil the reshaped electron-donating and -withdrawing nature in one molecular system. 1h-1j with peripherally strong amino donors exhibit an intense and broad intramolecular charge transfer absorption band in the near-infrared region from 550 to 900 nm. The molecular design and synthesis reported here broaden the types and fields of D-A molecular systems for potential applications in organic optoelectronic devices.

The Effect of TCNE and TCNQ Acceptor Units on Triphenylamine‐Naphthalenediimide Push‐Pull Chromophore Properties

AbstractAsymmetrical and symmetrical push‐pull chromophore‐based on triphenylamine (TPA) donors and naphthalenediimide (NDI) acceptors are designed and successfully synthesized via [2+2] cycloaddition‐retroelectrocyclization (CA‐RE) reaction with well‐known electron‐accepting tetracyanoethylene (TCNE) and 7,7,8,8, ‐tetracyanoquinodimethane (TCNQ) groups. The novel series of compounds NDI‐TPA‐1 to NDI‐TPA‐6 were characterized to identify the influence of the TCNE and TCNQ π‐conjugated linkers on the optical, electrochemical, and electronic properties of these molecules. We found that in dichloromethane the NDI‐TPAs 1, 4, 5, and 6 display absorbance peaks at increasing wavelengths 605, 641, 646, and 645 nm, respectively. We demonstrated that through simple chemical modification we could drop the lowest occupied molecular orbital of NDI‐TPA‐1 to 6. Furthermore, NDI‐TPA‐1 to 6 were integrated into organic thin‐film transistors (OTFTs) via spin‐coating technique, and charge transfer properties were investigated. We found that the choice of the functional group led to either p‐type, n‐type, or ambipolar characteristics.

Diastereoselective Synthesis of 1,2-Dihydrobenzofuro[3,2-b]pyridines via a Carbon-Carbon Double-Bond Cleavage/Rearrangement Cascade.

A new Lewis acid-catalyzed [2 + 2] cycloaddition/retroelectrocyclization (CA-RE)/1,6-addition relay of aurone-derived 1-azadienes and 1-alkynylnaphthalen-2-ols has been reported, leading to the regio- and diastereoselective synthesis of 1,2-dihydrobenzofuro[3,2-b]pyridine with a chiral carbon center and an axial chirality in good yields. This protocol enables the C-C double-bond scission/recombination to rapidly construct aza-heterocyclic architectures and features 100% atom utilization, a wide substrate scope, good compatibility with substituents, and excellent diastereoselectivity.

1,1,4,4-Tetracyanobutadiene-Functionalized Anthracenes: Regioselectivity of Cycloadditions in the Synthesis of Small Near-IR Dyes.

Two small 1,1,4,4-tetracyanobutadiene-functionalized chromophores were obtained by careful leverage of the regioselectivity of the cycloaddition reaction of tetracyanoethylene with anthracene–ynamide derivatives, inducing either a [2 + 2] or a [4 + 2] Diels–Alder process. DFT calculations unraveled the mechanism of the [2 + 2] cycloaddition–retroelectrocyclization reaction sequence with ynamides and elucidated the differing mechanisms in the two substrates. The synthesized dyes presented panchromatic absorption extending into the near-IR and far-red/near-IR photoluminescence in the solid state up to 1550 nm.

Synthesis of 1,1,4,4‐Tetracyanobuta‐1,3‐Dienes using Tetracyanoethylene Oxide via [3+2]‐Cycloaddition‐Ring Opening Reaction

AbstractUnlike the [3+2] cycloadduct of electron‐donating group (EDG)‐free alkynes with tetracyanoethylene oxide (TCNEO), the EDG induced [3+2] cycloadduct underwent one‐pot ring‐opening and deoxygenation reactions to provide the established EDG‐substituted non‐planar 1,1,4,4‐tetracyanobuta‐1,3‐dienes (TCBDs) push‐pull chromophores. This is an alternate synthetic method that provides access to TCBDs other than the [2+2] cycloaddition–retroelectrocyclization reactions with tetracyanoethene.

Building Conjugated Donor-Acceptor Cross-Links into Metal-Organic Frameworks for Photo- and Electroactivity.

We convert a coordination network into a covalent solid, while maintaining the crystallinity and greatly enhancing the framework rigidity and redox-active and photochemical properties. Specifically, intensely light-absorbing push-pull functions are postsynthetically installed by reacting the electrophilic TCNE (tetracyanoethylene) guests and the electron-rich alkyne side arms on a microporous Zr-organic framework, generating black microporous crystallites with a band gap smaller than 1.0 eV. The reaction proceeds in the known [2 + 2] cycloaddition-retroelectrocyclization mechanism and extensively establishes conjugated (polyene) bridges across the linker molecules. The donor (4-methoxyphenyl) and acceptor (dicyanovinyl) couples of the polyene bridges also act as an efficient fluorescent quencher and can be selectively installed in a thin outer layer of the host crystallite to form a core-shell assembly for turn-on fluorescent sensing of small amine molecules in water solutions.