An Update on General Chemiexcitation Mechanisms in Cyclic Organic Peroxide Decomposition and the Chemiluminescent Peroxyoxalate Reaction in Aqueous Media†

Four-membered ring peroxides are intimately linked to chemiluminescence and bioluminescence transformations, as high-energy intermediates responsible for electronically excited-state formation. The synthesis of 1,2-dioxetanes and 1,2-dioxetanones enabled mechanistic studies on their decomposition occurring with the formation of electronically excited carbonyl products in the singlet or triplet state. The third member of this family, 1,2-dioxetanedione, has been postulated as the intermediate in the peroxyoxalate reaction, recently confirmed by kinetic studies on peroxalic acid derivatives. Several general chemiexcitation mechanisms have been proposed as model systems for the chemiexcitation step in efficient bioluminescence and chemiluminescence transformations. In this review article, we discuss the validity and efficiency of the most important chemiexcitation mechanisms, extended to aqueous media, where the efficiency is known to be drastically reduced, specifically in the peroxyoxalate reaction, highly efficient in anhydrous environment, but much less efficient in aqueous media. Mechanistic studies of this reaction will be discussed in diverse aqueous environments, with special attention to the catalysis involved in the thermal reaction leading to the formation of the high-energy intermediate and to the chemiexcitation mechanism, as well as emission quantum yields. Finally, several recent analytical and bioanalytical applications of the peroxyoxalate reaction in aqueous media will be given.     

Chemiexcitation Efficiency of Intermolecular Electron‐transfer Catalyzed Peroxide Decomposition Shows Low Sensitivity to Solvent‐cavity Effects

Intermolecular chemically initiated electron exchange luminescence (CIEEL) systems are known to possess low chemiluminescence efficiency; whereas, the corresponding intramolecular transformations are highly efficient. As the reasons for this discrepancy are not known, we report in this work our studies of the solvent‐cavity effect on the efficiency of two intermolecular CIEEL systems, the catalyzed decomposition of diphenoyl peroxide and of a relatively stable 1,2‐dioxetanone derivative, spiro‐adamantyl‐1,2‐dioxetanone. The results indicate a very low medium viscosity effect on the quantum yields of these systems, a priori not compatible with these bimolecular transformations, showing also that their low efficiency cannot be due to solvent‐cavity escape of intermediate radical ion pairs. In addition, the solvent‐cage effect on the CIEEL efficiency, after the occurrence of the initial electron transfer, proved also to be very low, indicating the intrinsic low viscosity effect on the chemiexcitation step. Therefore, it is concluded that the low efficiency of these systems is intrinsic to the chemiexcitation step and cannot be improved by medium viscosity effects, being possibly due to sterical hindrance on charge‐transfer complex formation in the initial step of the CIEEL.     

Mechanistic Studies on the Salicylate-Catalyzed Peroxyoxalate Chemiluminescence in Aqueous Medium

The peroxyoxalate reaction is one of the most efficient chemiluminescence transformations known and the only system occurring by an intermolecular chemically initiated electron exchange luminescence (CIEEL) mechanism with confirmed high quantum yields. The peroxyoxalate chemiluminescence (PO-CL) is mainly studied in anhydrous organic medium; however, for bioanalytical application, it should be performed in aqueous media. In the present work, we study the peroxyoxalate system in a binary 1,2-dimethoxyethane/water mixture with bis(2,4,6-trichlorophenyl) oxalate (TCPO), bis(4-methylphenyl) oxalate (BMePO) and bis[2-(methoxycarbonyl)phenyl] oxalate (DMO), catalyzed by sodium salicylate, in the presence of rhodamine 6G as activator. Reproducible kinetic results are obtained for all systems; emission decay rate constants depend on the salicylate as well as hydrogen peroxide concentration, and the occurrence of a specific base catalysis is verified. Although singlet quantum yields determined are lower than in anhydrous media in comparable conditions, they are still considerably high and adequate for analytical applications. The highest singlet quantum yields are obtained for the “ecologically friendly” derivative DMO indicating that this derivative might be the most adequate substrate for the use of the peroxyoxalate system in bioanalytical applications.     

Watching photoinduced chemistry and molecular energy flow in solution in real time

Energized molecules are the essential actors in chemical transformations in solution. As the rearrangement of bonds requires a movement of nuclei, vibrational energy is often the driving force for a reaction. Vibrational energy can be redistributed within the "hot" molecule, or relaxation can occur when molecules interact. Both processes govern the rates, pathways, and quantum yields of chemical transformations in solution. Unfortunately, energy transfer and the breaking, formation, and rearrangement of bonds take place on ultrafast timescales. This Review highlights experimental approaches for the direct, ultrafast measurement of photoinduced femtochemistry and energy flow in solution. In the first part of this Review, we summarize recent experiments on intra- and intermolecular energy transfer. The second part discusses photoinduced decomposition of large organic peroxides, which are used as initiators in free radical polymerization. The mechanisms and timescales of their decarboxylation determine the initial steps of polymerization and the microstructure of the polymer product.     

BF3⋅OEt2‐Catalyzed Intermolecular Reactions of Vinylidenecyclopropanes with Bis(p‐alkoxyphenyl)methanols: A Novel Cationic 1,4‐Aryl‐Migration Process

BF₃?OEt₂‐catalyzed reactions of vinylidenecyclopropanes (VDCPs) 1 with bis(aryl)methanols 2 were thoroughly investigated. When VDCPs 1 reacted with electron‐rich bis(aryl)methanols 2 , diastereomeric rotamers of indene derivatives formed in excellent yields by a novel cationic 1,4‐aryl migration between two carbon atoms and the subsequent intramolecular Friedel–Crafts reaction pathways in the presence of BF₃?OEt₂ under mild conditions. As for electron‐deficient or less‐electron‐rich bis(aryl)methanols 2 , either trialkene products formed in good yields by direct deprotonation, or another type of indene derivative was produced by direct intramolecular Friedel–Crafts reaction, depending on the substituents on the cyclopropane of VDCPs. In addition, DFT calculations were carried out to explain the experimental results. Plausible mechanisms for all these transformations are proposed on the basis of the experimental and computational results.     

Trajectory surface hopping molecular dynamics on Chemiluminescence of cyclic peroxides

Chemiluminescence (CL) of peroxides is one of the most highly sensitive and most useful analytical techniques. Although the mechanisms of CL were studied experimentally and theoretically in the past decades, the chemiexcitation that a ground-state specie being excited from its electronic ground state to yield excited-state products by a chemical reaction is still not completely understood. Direct dynamics simulation on CL reaction which takes into account the full complexity of the relevant potential energy surface characterizes nonadiabatic processes involved in chemiexcitation and could provide access not only to the available reaction channels but also to statistical quantities such as reaction times and quantum yields. In the last decade, the trajectory surface hopping (TSH) molecular dynamics (MD) which is one of the mixed quantum-classical approaches is hence adopted to simulate the nonadiabatic process in CL of cyclic peroxides. In this article, the basic principle of TSH-MD and the successful applications on the CL reactions were shortly review.     

An Efficient Synthesis of Benzazocines by Gold(I)‐Catalyzed Tandem 1,2‐Acyloxy Shift/[3+2] Cycloaddition of Terminal 1,9‐Enynyl Esters

An effective synthesis of structurally diverse benzazocines was accomplished in good to excellent chemical yields (55–82 %) through a gold(I)‐catalyzed cascade reaction involving tandem 1,2‐acyloxy shift/[3+2] cycloaddition of terminal 1,9‐enynyl esters. The reaction proceeds under extremely mild conditions and represents one of the relatively few transition‐metal‐catalyzed intramolecular cycloaddition reactions for the synthesis of benzazocines.     

Theoretical study on the thermodynamic properties and self-decomposition of methylbenzenediol isomers

Alkylated hydroxylated aromatics are major constituents of various types of fuels, including biomass and low-rank coal. In this study, thermochemical parameters are obtained for the various isomeric forms of methylbenzenediol isomers in terms of their enthalpies of formation, entropies, and heat capacities. Isodesmic work reactions are used in quantum chemical computations of the reaction enthalpies for O-H and H?C-H bond fissions and the formation of phenoxy- and benzyl-type radicals. A reaction potential energy on the singlet-state surface surface is mapped out for the unimolecular decomposition of the 3-methylbenzene-1,2-diol isomer. According to the calculated high pressure-limit reaction rate constants, concerted hydrogen molecule elimination from the methyl group and the hydroxyl group, in addition to intermolecular H migration from the hydroxyl group, dominates the unimolecular decomposition at low to intermediate temperatures (T ≤ 1200 K). At higher temperatures, O-H bond fission and concerted water elimination are expected to become the sole decomposition pathways.     

Insights into the N‐Heterocyclic Carbene (NHC)‐Catalyzed Intramolecular Cyclization of Aldimines: General Mechanism and Role of Catalyst

One of the most challenging questions in the Lewis base organocatalyst field is how to predict the most electrophilic carbon for the complexation of N‐heterocyclic carbene (NHC) and reactant. This study provides a valuable case for this issue. Multiple mechanisms (A, B, C, D, and E) for the intramolecular cyclization of aldimine catalyzed by NHC were investigated by using density functional theory (DFT). The computed results reveal that the NHC energetically prefers attacking the iminyl carbon (AIC mode, which is associated with mechanisms A and C) rather than attacking the olefin carbon (AOC mode, which is associated with mechanisms B and D) or attacking the carbonyl carbon (ACC mode, which is associated with mechanism E) of aldimine. The calculated results based on the different reaction models indicate that mechanism A (AIC mode), which is associated with the formation of the aza‐Breslow intermediate, is the most favorable pathway. For mechanism A, there are five steps: (1) nucleophilic addition of NHC to the iminyl carbon of aldimine; (2) [1,2]‐proton transfer to form an aza‐Breslow intermediate; (3) intramolecular cyclization; (4) the other [1,2]‐proton transfer; and (5) regeneration of NHC. The analyses of reactivity indexes have been applied to explain the chemoselectivity, and the general principles regarding the possible mechanisms would be useful for the rational design of NHC‐catalyzed chemoselective reactions.     

Construction of the Benzomesembrine Skeleton: Palladium(0)‐Catalyzed Intermolecular Arylative Dearomatization of α‐Naphthols and Subsequent Aza‐Michael Reaction

A novel palladium(0)‐catalyzed intermolecular arylative dearomatization of α‐naphthols and subsequent aza‐Michael reaction is described. Two adjacent stereocenters were constructed efficiently through consecutive arylative dearomatization and Michael addition reactions. By utilizing this method, structurally diverse benzomesembrine derivatives were synthesized with excellent yields and chemoselectivity. The benzomesembrine products were shown to undergo versatile functional‐group transformations.     

Construction of Fused Pyrrolidines and β‐Lactones by Carbene‐Catalyzed C−N,C−C,and C−O Bond Formations

A carbene‐catalyzed intermolecular C−N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused β‐lactones, is disclosed. The nitrogen‐containing bicyclic β‐lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene‐catalyzed asymmetric carbon–heteroatom bond‐forming reactions.     

Construction of Fused Pyrrolidines and β‐Lactones by Carbene‐Catalyzed C−N,C−C,and C−O Bond Formations

A carbene‐catalyzed intermolecular C−N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused β‐lactones, is disclosed. The nitrogen‐containing bicyclic β‐lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene‐catalyzed asymmetric carbon–heteroatom bond‐forming reactions.     

Gold‐Catalyzed Cycloisomerization of Yne‐Vinylidenecyclopropanes: A Three‐Carbon Synthon for [3+2] Cycloadditions

A novel type of yne‐vinylidenecyclopropanes (VDCPs) has been synthesized and applied in gold‐catalyzed cycloisomerization reactions. It was found that these compounds can undergo an intramolecular cycloisomerization and perform as a three‐carbon synthon for [3+2] cycloaddition under gold catalysis to give fused [4.3.0] and [5.3.0] bicyclic derivatives and VDCP rearranged products in moderated to good yields under mild conditions. The substrate scope of these novel transformations has been explored and plausible reaction mechanisms have been presented on the basis of deuterium labeling experiments and DFT calculations.     

Peroxyoxalate chemiluminescence of N,N'-bistosyl-1H,4H-quinoxaline-2,3-dione and related compounds. Dependence on electronic nature of fluorophores

The title compound N,N'-bistosyl-1H,4H-quinoxaline-2,3-dione (TsQD) provides peroxyoxalate chemiluminescence (PO-CL) when reacted with hydrogen peroxide in the presence of fluorophores. The chemiluminescence (CL) efficiency of TsQD was superior to that of other related compounds such as bis(2,4,6-trichlorophenyl) oxalate (TCPO), a typical oxalate for the peroxyoxalate PO-CL, under an aqueous condition. Factors affecting the PO-CL efficiency are discussed from the viewpoint of the structures of the substrates and the electronic nature of the fluorophores. A linear correlation of the logarithmic values evaluated from the CL quantum yields with the oxidation potentials of the aromatic fluorophores supports the involvement of the chemically initiated electron exchange luminescence (CIEEL) mechanism in both TsQD- and TCPO-CL systems. Also, an excellent Hammett relationship was derived from the correlation between the sigma(+) values and the relative singlet excitation yields in TsQD-CL enhanced by a series of fluorescent para,para'-disubstituted distyrylbenzenes.     

Chain‐transfer reaction in the radical polymerization of di‐n‐butyl itaconate at high temperatures

Radical polymerizations of di‐n‐butyl itaconate were investigated. Unexpected resonances (C resonances) were observed in ¹³C NMR spectra of C?O of poly(di‐n‐butyl itaconate)s [poly(DBI)s] obtained at temperatures higher than 60 °C, although two kinds of carbonyl groups showed splittings due to triad tacticities in the spectra of polymers obtained at lower temperatures. The poly(DBI)s formed by the different kinds of initiators or formed in the presence of chain‐transfer agents showed hardly any changes in the intensities of the C resonances; this indicated that the C resonances were not due to the structures formed through initiating and terminating reactions. The poly(DBI)s obtained at different yields showed only a slight increase in the intensities of the C resonances with the yield, which suggested that the C resonances were not attributable to the intermolecular chain‐transfer reaction to the monomer and/or polymer. However, the intensities of the C resonances significantly increased with a decreasing feed monomer concentration; this suggested that intramolecular chain‐transfer reactions took place at high temperatures. Furthermore, a Cu complex‐catalyzed atom transfer radical polymerization mechanism was revealed to be effective for suppressing the intramolecular chain‐transfer reaction at 60 °C. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2415–2426, 2002     

Exploring transition state structures for intramolecular pathways by the artificial force induced reaction method

Finding all required transition state (TS) structures is an important but hard task in theoretical study of complex reaction mechanisms. In the present article, an efficient automated TS search method, artificial force induced reaction (AFIR), was extended to intramolecular reactions. The AFIR method has been developed for intermolecular associative pathways between two or more reactants. Although it has also been applied to intramolecular reactions by dividing molecules manually into fragments, the fragmentation scheme was not automated. In this work, we propose an automated fragmentation scheme. Using this fragmentation scheme and the AFIR method, a fully automated search algorithm for intramolecular pathways is introduced. This version for intramolecular reactions is called single‐component AFIR (SC‐AFIR), to distinguish it from multicomponent AFIR for intermolecular reactions. SC‐AFIR was tested with two reactions, the Claisen rearrangement and the first step of cobalt‐catalyzed hydroformylation, and successfully located all important pathways reported in the literature. © 2013 Wiley Periodicals, Inc.     

Highly selective intra- and intermolecular coupling reactions of diazo compounds to form cis-alkenes using a ruthenium porphyrin catalyst

[Ru(2,6-Cl(2)TPP)(CO)] catalyzed intramolecular coupling reactions of bisdiazoacetates and intermolecular coupling reactions of monodiazoacetates to afford the coupling products in up to 76% and 93% yields, respectively. Only the cis isomers were obtained from the reactions. Employing such a ruthenium-catalyzed coupling reaction of a diazo compound as a key step allowed the synthesis of Patulolide B in 67% yield with a ratio of >40:1 against its trans isomer.     

Peroxyoxalate High‐Energy Intermediate is Efficiently Decomposed by the Catalyst Imidazole

The peroxyoxalate reaction is a highly efficient chemiluminescence system, its chemiexcitation process involving the intermolecular interaction between an activator (ACT) and the high‐energy intermediate (HEI) of the reaction. Typically, the HEI is generated through the reaction of an oxalate ester with H₂O₂, in the presence of a basic/nucleophilic catalyst, such as imidazole (IMI‐H). IMI‐H, besides catalyzing the formation of the HEI, is also known to decompose this peroxidic intermediate. Despite that, up to now, no rate constant value has been determined for such significant interaction. Through kinetic measurements, we have observed that IMI‐H is roughly four times more efficient than 9,10‐diphenylanthracene (DPA), a classic ACT, in catalyzing the decomposition of the HEI by a bimolecular electron transfer reaction through a Chemically Initiated Electron Exchange Luminescence‐like process. For instance, when IMI‐H and DPA are at the same concentration, 78% of the generated HEI is actually consumed by the nonemissive bimolecular interaction with IMI‐H. We have obtained an average singlet excited state formation quantum yield, at infinite ACT concentration, of (5.5 ± 0.5) × 10^?2 E mol^?1, determined at five different IMI‐H concentrations. This ultimately suggests that the yield of formation of HEI actually does not depend on the IMI‐H concentration.     

Palladium‐Catalyzed Intermolecular Oxidative Coupling Reactions of (Z)‐Enamines with Isocyanides through Selective β‐C(sp2)‐H and/or C=C Bond Cleavage

Herein, two efficient palladium‐catalyzed intermolecular oxidative coupling reactions of (Z)‐enamines with isocyanides via selective β‐C(sp²)‐H and/or C=C bond cleavage have been developed, leading to controllable chemodivergent and stereoselective construction of a wide range of (E)‐β‐carbamoylenamine derivatives containing strong intramolecular hydrogen bonds. Furthermore, possible reaction pathways for these transformations are proposed on the basis of preliminary mechanism studies.     

Rhodium‐Catalyzed Diastereoselective Cyclization of Allenyl‐Sulfonylcarbamates: A Stereodivergent Approach to 1,3‐Aminoalcohol Derivatives

A diastereoselective and stereodivergent rhodium‐catalyzed intramolecular coupling of sulfonylcarbamates with terminal allenes is described and it provides selective access to 1,3‐aminoalcohol derivatives, scaffolds found in bioactive compounds. The reaction is compatible with a large range of different functional groups, thus furnishing products with high diastereoselectivities and yields. Moreover, multigram scale reactions, as well as the application of suitable product transformations were demonstrated.