Journal articles on the topic 'Reverse Diels-Alder'

Fullerenes and endohedral metallofullerenes (EMFs) are molecular building blocks for a variety of organic materials widely applicable in photovoltaics, catalysis, quantum information science, semi-conductors, biomedicines, and so on. Regioselective functionalization reactions are essential for the construction of fullerene and EMF materials. Multicomponent reactions that generate reactive species to be captured by the double bonds on fullerenes or EMFs represent a useful approach to develop new reactions. In this presentation we hope to share our recent work in the development of new reactions for fullerene and EMF functionalizations, including isocyanide-induced reactions, reverse electron demand Diels-Alder reactions, and aminations.

A number of arynes, generated by treatment of haloarenes with sodium or potassium amide in tetrahydrofuran, were trapped with furan. The resulting dihydro epoxy arenes were converted into the following annulated isobenzofuran derivatives by using reverse Diels-Alder methodology: naphtho[l,2-clfuran, phenanthro[9,10-elfuran, pyreno[l,2-elfuran, pyreno[3,4- elfuran, anthra[l,2- elfuran, phenanthro[l,2- clfuran and phenanthro[3,4- elfuran. Bimolecular rate constants for the addition of maleic anhydride to these furans were measured, and were correlated with the Herndon structure count. Addition of arynes to selected members of this furan series yielded adducts which were deoxygenated to afford polycyclic aromatic hydrocarbons.

The use of polyaromatic hydrocarbons to capture and release singlet oxygen is of considerable importance in materials chemistry, synthesis, and photodynamic therapy. Here we studied the ability of a series of tethered twistacenes, possessing different degrees of backbone twist, to capture and release singlet oxygen via the reversible Diels–Alder reaction. When the twistacene acts as both a sensitizer and a diene, the photo-oxidation rate depends on the extinction coefficient of the irradiation wavelength. However, when the twistacenes function solely as a diene, the rate of photo-oxidation increases with increasing twist. The rate of the reverse reaction, the singlet oxygen release, also increases with increasing twist. The calculated transition state energy decreases with increasing twist, which can explain the observed trend. The presence of the tether significantly increases the reversibility of the reaction, which can proceed in repeated forward and reverse cycles in very high yield under mild conditions, as required for molecular switches.

A one-step swelling and polymerization technique was used in the synthesis of porous glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EGDMA) monodisperse polymeric microspheres. The polystyrene (PS) seed obtained in the dispersion polymerization was used as a shape template. The presence of epoxide rings in the chemical structure of microspheres enables their post-polymerization chemical modifications involving: the Diels-Alder reaction with sodium cyclopentadienide and maleic anhydride, the reaction with 4,4′-(bismaleimido)diphenylmethane, and the thiol-Michael reaction with methacryloyl chloride and 2-mercaptopropionic acid. Changing the reaction mixture composition—the amounts of crosslinking monomer and PS seed as well as the type and concentration of porogen porous microspheres of different porous structures were obtained. Their porous structures were characterized in the dry and swollen states. The copolymers obtained from the equimolar monomers mixture modified in the above way were applied as the column packing materials and tested in the reverse-phase HPLC (High-Performance Liquid Chromatography). A few factors influencing morphology and porous structure of microspheres were studied.

The review is devoted to research in the field of "marine" diterpene metabolites of the 4,7-oxaeunicellan type, which have a taxol-like mechanism of cytotoxic action. The known most effective chemical syntheses are presented, as well as the results of our own research, on the basis of which, based on (+)-δ-cadinol, the formal synthesis of eleuthesides was realized, and the synthesis of analogs of sorcrdictyin A and eleutherobin was carried out from the Diels-Alder adduct of levogluclsenone and piperylene. In the course of the research, the features of the chemical behavior of the little-studied sesquiterpene (+)-δ-cadinol, isolated from the resin of the Siberian cedar Pinus sibirica R.Mayer, were revealed, which caused certain difficulties at the initial stage of research when developing a scheme for the synthesis of eleuthesides. Thus, the ozonolytic cleavage of the double bond, regardless of the reaction conditions, was accompanied by α-ketol rearrangement and aldol cyclization. Both problems were solved by protecting the aldehyde group into dimethyl acetal, and the hydroxyl groups by intramolecular oxacyclization into 1,4-epoxide. After the construction of the "upper" and "lower" side chains, the reverse transition from the 1,4-epoxide to the linear structure was carried out by the action of BF3·Et2O-Ac2O to obtain a diacetate derivative corresponding to the key synthon of the synthesis scheme of Nicolau et al., which completed the formal synthesis of eleuthesides. Based on the analysis of literature data on the properties of N-methylurocanoic acid and its role in sarcodictyins, an assumption was made about the manifestation of cytotoxic properties by more accessible esters of the little-studied N-methylurocanoic acid. In this regard, methods have been developed for obtaining esters of urocanic acid from histidine and glucose and its N-methylation. Then, esters of N-methylurocanoic acid were synthesized with a number of alcohols, including those of natural origin. Using a similar strategy, a scheme was developed for the synthesis of the structural core of an eleutheside analog with a 14-methylcyclohexene ring A starting from the Diels-Alder adduct of levoglucosenone and piperylene. The key step of the scheme is the intramolecular acetylenealdehyde cyclization into a 10-membered carbocycle, which completes the construction of the eleutheside core. Trichloroacetimidate, a glycosylation agent in the synthesis of eleutherobin, was obtained. Synthetic studies have been completed by obtaining analogs of sarcodictin A with a 14-methylcyclohexene ring A and an analog of eleutherobin with a similar ring A and an orthoester arabinose substituent.

A combination of MM3-level molecular mechanics calculations and PM3-level semiempirical molecular orbital calculations has been employed, in conjunction with an algorithm for the comprehensive conformational analysis of cyclic compounds, to obtain 1202 unique 1,3,9-cyclotetradecatriene conformations, distributed over the six possible geometrical isomers, and 70 unique transannular Diels–Alder transition structures leading to the six possible stereoisomeric tricyclic olefins. A kinetic analysis that takes into account all minima of a given geometrical isomer and all transition structures leading to the same tricyclic product leads to a free energy of activation that is almost the same as the free energy difference between the lowest minimum and the lowest transition structure (the Curtin–Hammett principle). A substantial template effect, mainly entropic in origin, is found when the transannular reactions are compared to the Diels–Alder reactions of the cognate 2,4-hexatrienes with the 2-butenes. Although the cyclization of the trans-cis-trans triene favours the cis-anti-cis over the trans-anti-trans product by more than 20 kcal mol–1, the situation is reversed in the acyclic reaction. A cyclic triene that can cyclize directly to a trans-anti-trans tricycle can therefore be proposed.Key words: molecular models, Deslongchamps, Takahashi, trans-anti-trans tricycle, MM3, PM3, transition states.

V. Rama Subbaraoa*
 aNatural Products Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology, Habsiguda, Hyderabad 500007, India.
 Study and optimization of Diels-Alder reaction of piperine in aqueous ionic solutions using Gn.HCl as a catalyst. The semi-synthesis of these products using intermolecular [4+2] cycloaddition reaction has been described. Obtained products were characterized using IR, HNMR, CNMR and Mass Spectroscopy.
 Introduction
 An outsized number of phenomena concern to and are conducted in liquid phase involving ionic species (Millions of years ago, Mother Nature discovered the secrets of water molecule) in different biological and other natural processes. Salt present in the oceans, a striking example from Nature, is a multi component salt solution reflecting the distant marine origin of life on earth together with the composition of physiological fluids. In general the ionic solutions play roles in several industrial and geological processes in addition to their deep impact on the biological molecules. This enormous power of ionic solutions is based on the interactions of ion with solvent. In this work, we present some interesting results with comprehensive implications on the application of ion-solvent (i-s) interactions on organic reactions.
 Ion-Solvent interactions
 Cohesion among molecules in the liquid phase results from intermolecular forces. These forces include hydrogen-bonding, dipole-dipole, multi polar, dispersion interactions and also interactions emerging from the repulsion between two molecules. The cohesion due to intermolecular forces gives rise to a 'pressure' which is experienced by the solvent molecules. A liquid undergoing a small, isothermal volume expansion does work against the cohesive forces which causes a change in the internal energy, U. The function (∂U/∂V)T, is called as internal pressure (Pi) of a liquid and is supported by the equation of state. Internal pressure increases upon the addition of some solutes like NaCl, KCI, etc. and decreases by salts like of guanidinium salts.
 Diels-Alder Reaction in aqueous medium
 For long time water was not a popular solvent for the Diels-Alder reaction. Before 1980 its use had been reported only incidentally. Diels and Alder themselves performed the reaction between furan and maleic acid in an aqueous medium in 1931,27 an experiment which was repeated by Woodward and Baer in 1948. 28 They noticed a change in endo-exo selectivity when comparing the reaction in water with ether. The extreme influence of water can exert on the Diels-Alder reaction was rediscovered by Breslow in 1980, much by coincidence 29,30 while studying the effect of β-cyclodextrin on the rate of a Diels-Alder reaction in water, accidentally.
 
 Schem 1.
 Alternatively, Grieco et al., have repeatedly invoked the internal pressure of water as an explanation of the rate enhancement of Diels-Alder reactions in these solvents. 31 They probably inspired by the well known large effects of the external pressure on rates of cycloadditions. However the internal pressure of water is very low and offers no valid explanation for its effects on the Diels-Alder reaction. The internal pressure is defined as the energy required bringing about an infinitesimal change in the volume of the solvent at constant temperature. Due to the open and relatively flexible hydrogen-bond network of water, a small change in volume of these solvents does not require much energy. A related, but much more applicable solvent parameter is the cohesive energy density. This quantity is a measure of energy required for evaporation of the solvent per unit volume. The reactions in water were less accelerated by pressure than those in organic solvents, which is in line with notion that pressure diminishes hydrophobic interactions.
 The effect of water on the selectivity of Diels-Alder reactions
 Three years after the Breslow report on the large effects of water on the rate of the Diels-Alder reaction, he also demonstrated that the endo-exo selectivity of this reaction benefits markedly from employing aqueous media. Based on the influence of salting-in and salting-out agents, Breslow pinpoints hydrophobic effects as the most important contributor to the enhanced endo-exo selectivity. Hydrophobic effects are assured to stabilize the more compact endo transition state more than the extended exo transition state. In Breslow option the polarity of water significantly enhances the endo-exo selectivity.
 In conclusion, the special influence of water on the endo-exo selectivity seems to be a result of the fact that this solvent combines in it three characteristics that all favors formation of the endo/exo adduct. 1. water is strong hydrogen bond donor 2. water is polar and water induces hydrophobic interactions.
 Study of salting-out and salting-in reagents towards the Diels-Alder reaction of piperine (1):
 The special effects of water as solvent for valuable Diels-Alder reaction (Scheme 1) of piperine (1), greatly altered by the addition of ionic solutes (Table 1) such as LiCl, LiBr, LiClO4,- NaCl, NaBr, KF, KCl, KBr, MgCl2, CaCl2, guanidinium chloride, guanidinium carbonate, guanidinium nitrate.
 Aqueous salts solutions accelerated cycloaddition reactions (Scheme 1) of piperine (1) to give resultant cycloadducts 2, 3 and 4 among them 2 is major ortho-exo cyclohexene type dimeric amide alkaloid and also known as chabamide, which is previously isolated from this plant, isomer 3 is also known adduct and previously isolated from Piper nigrum. 21 Cycloadduct 4 was synthesized from piperine by Diels-Alder reaction by Wei. et al. its physical and spectroscopic data were identical with reported data22 (1H-NMR & Mass spectra).
 
 
 Table 1: Study of different salts towards the Diels-Alder reaction of piperine (1).
 
 aOverall yield of adducts after HPLC, un-reacted piperine was recovered in all reactions.
 Reaction showed good overall yield and more exo selectivity. This reaction showed completely regioselectivity (yield of 2+3>4) due to maximum involvement of α-double bond rather than γ-double bond of 1 during Diels-Alder reaction.
 Table 2: Comparision of salting-out and salting-in reagents towards the Diels-Alder reaction of piperine (1).
 
 Study of Salting-out reagents
 Increased rate in Diels-Alder reaction (over all yield up to 79 %) of piperine (1) has been attributed to the hydrophobic effect. Owing to the difference in polarity between water and the reactants, water molecules tend to associate amongst themselves, excluding the organic reagents and forcing them to associate together forming small drops surrounded by water.
 A further method of increasing the rate of Diels-Alder reaction in water is so called ‘salting-out’ effect. Among the salting-out reagents used (Table 1) in this methodology CaCl2 is the best reagent and gave 79 % over all yield. If anion size increases, reaction yield decreases, where as cation size increases, reaction yield increases. Here a salt such as calcium chloride is added to the aqueous solution. In this case water molecules attracted to the polar ions, increasing the internal pressure and reducing the volume. This has the effect of further excluding the organic reagents. For reactions such as Diels-Alder, which have negative activation volumes, the rates are enhanced by this increase in internal pressure in much the same way as expected for an increase in external pressure. This salting-out reagent showed good exo selectivity, due to formation of cycloadduct 2 (ortho-exo) is major up to 69 % (cycloadduct ratio) compare to cycloadducts 3 (21 %, meta-exo) and 4 (10%, meta-exo) are poor in yield.
 
 Schem 2.
 Plausible mechanism of Diels-Alder reaction catalyzed by Gn.HCl.
 Study of Salting-in reagents
 Among the tested salting-in reagents used in this methodology (Table 1) guanidinium chloride (Gn.HCL) is the best reagent and gave 81 % overall yield, where as LiClO4 end up with only 15 % overall yield. Gn.HCL reagent exhibited well selectivity towards the Diels-Alder reaction of piperine in given conditions (scheme 1). Formation of cycloadduct 2 in 80 %, 3 in 15 % and 4 in 5 % ratio is clearly indicates this methodology received good attention towards the exo selectivity in Diels-Alder reaction of piperine. Overall yield is also high with salting-in reagents when compare to salting-out reagents.
 Procedure for aqueous ionic salts catalyzed Diels–Alder reactions of piperine (1):
 To a stirred mixture of piperine (1) (50.0 mg, 0.175 mmol), 6M aqueous guanidinium. Hydrochloride (2 mL) in a round bottom flask fitted with condenser and refluxed for 70 h in an oil bath. After completion of the reaction, monitored by TLC (dipped in 5% solution of phosphomolybdic acid in methanol and heating), the reaction mixture was cooled to room temperature and diluted with water (3 mL). Then extracted with EtOAc (2x5 mL), the combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue obtained was then purified by reversed-phase (RP) HPLC (column: Phenomenex Luna C18, 250 x 10 mm, 10µ), solvent system: 80% acetonitrile in water, flow rate: 1.5 mL/min, to give pure compounds of adducts (2) 0.065 g, (3) 0.012 g and (4) 0.004 g.
 Cycloaddition reaction between piperine (1a) and pellitorine (1b):
 Our aim of this cycloaddition reaction is to explain to study different cycloadducts and selectivity of diene among piperine and pellitorine (Scheme 4). This biomimetic synthesis will explain the probability of diene, which participated in Diels-Alder reaction between piperine (1a) and pellitorine (1b) both were isolated from same plant (P. chaba). Nigramide N, which is formed biosynthetically via cycloaddition reaction between piperine and pellitorine, this adduct previously isolated from roots of P. nigrum 21 by Wei. et. al.
 Lewis acid catalyzed cycloaddition reactions of piperine (1a) and pellitorine (1b) under organic and aqueous solvent conditions to give resultant cycloadducts 2c, 3c, 4c, 2a and 3b. Cycloadduct 2c and 3c is new cycloadducts and their structures were illustrated by 1D and 2D spectral data.
 Structure elucidation of compound 2c:
 Compound 2c was obtained as pale yellow liquid. The molecular formula of 2c was established as C31H44N2O4 by HRESIMS (Fig-18), which provided a molecular ion peak at m/z 509.3381 [M++H], in conjunction with its 13C NMR spectrum (Fig-12). The IR spectrum displayed absorption bands diagnostic of carbonyl (1640 cm-1) (Fig-10). The 300 MHz 1H NMR spectrum (in CDCl3) indicated the presence of two signals at δ 5.86 (dd, J = 15.6, 10.1 Hz) and 6.27 (d, J = 15.6 Hz), which were assigned to trans-olefinic protons by the coupling constant of 15.6 Hz. It also displayed aromatic protons due to two 1, 3, 4-trisubstituted aromatic rings at δ 6.82 (1H, br s), 6.76 (1H, dd, J = 7.8, 1.4 Hz), 6.75 (1H, d, J = 7.8 Hz) (Fig-11), (Table 4).
 In addition to the above-mentioned moieties, combined inspection of 1H NMR and 1H–1H COSY revealed the presence of cyclohexene ring, one isobutylamide and one pyrrolidine ring.
 
 The 13C NMR spectrum (Fig-12) displayed the presence of 31 carbon atoms and were further confirmed by DEPT experiments (Fig-13) into categories of 11 methylenes, 12 methines and 5 quaternary carbons including two carbonyls (δ 173.01 and 172.50). On the basis of these characteristic features, database and literature search led the skeleton of compound 2c as a dimeric alkaloidal framework.
 A comprehensive analysis of the 2D NMR data of compound 2c facilitated the proton and carbon assignments. 1H–1H COSY spectrum (Fig-16) suggested the sequential correlations of δ 3.51 (dq, J = 5.0, 2.6 Hz)/5.62 (dt, J = 9.8, 2.6 Hz)/6.10 (ddd, J = 9.8, 1.5 Hz)/2.20 (m)/2.72 (ddd, J = 11.1, 10.1, 5.2 Hz)/3.35 (dd, J = 11.1, 9.8 Hz) assignable to H-2-H-3-H-4-H-5-H-3"-H-2" of the cyclohexene ring.
 
 Concerning the connections of the n-amyl and 3, 4-methylenedioxy styryl groups, HMBC spectrum (Fig-15) showed correlations of H-4, H-6, H-7/C-5; H-5", H-4"/C-3", which implies that these units were bonded to the cyclohexene ring at C-5 and C-3". Further, HMBC correlations of two methylene protons at δ 5.95 with 147.91 (C-8"), 146.87 (C-9"), confirmed the location of methylenedioxy group at C-8", and C-9". Remaining units, isobutylamine and pyrrolidine (rings) were connected through carbonyl groups at C-2 and C-2", which was confirmed by HMBC correlations of H-2 and H-1' to C-1 (δ 173.01) and H-2" and H-1''' to C-1" (δ 172.50).
 
 The assignment of the relative configuration of compound 2c, and confirmation of overall structure were achieved by the interpretation of the NOESY spectral data and by analysis of 1H NMR coupling constants. The large vicinal coupling constants of H-2"/H-2 (11.1 Hz) and H-2"/H-3" (11.1 Hz) indicated anti-relations of H-2"/H-2 and H-2"/H-3" and the axial orientations for these protons. In the NOESY spectrum (Fig-17), the occurrence of the correlations between H-2/H-3" and the absence of NOE effects between H-2/H-2" and H-2"/H-3" supported the above result. This data indicated β-orientation for H-2" and α-orientation for H-2 and H-3". The α-orientation of H-5 was suggested by the coupling constant of H-5/H-3" (5.2 Hz) and the absence of the NOESY correlations between H-3" and H-2". On the basis of these spectral data, the structure of compound 2c was unambiguously established and trivially named as chabamide M.
 Compound 3a:
 IR (KBr) nmax: 2923, 2855,1628, 1489, 1242, 1128, 1035 cm-1
 d ppm 0.69 & 1.25 (2H, m, H-2'"), 1.15 & 1.23 (2H, m, H-4'"), 1.31 & 1.40 (2H, m, H-3'"), 1.52 (2H, m, H-2'), 1.56 (2H, m, 4'), 1.61 (2H, m, H-3'), 2.94 (1H, td, J = 10.1, 10.1, 5.5 Hz, H-3"), 3.02 & 3.60 (2H, m, H-5'"), 3.09 & 3.32 (2H, m, H-1'"), 3.51 (2H, m, H-1'), 3.61 (1H, m, H-2), 3.61 (2H, m, H-5'), 3.78 (1H, dq, J = 10.0, 2.3 Hz, H-5), 4.07 (1H, t, J = 10.1, H-2"), 5.72 (1H, ddd, J = 9.8, 5.0, 2.7 Hz, H-3), 5.88 (2H, s, H-12), 5.89 (1H, dt, 10.3, 1.8 Hz, H-4), 5.90 (1H, J =15.8, 9.8 Hz, H-4"), 5.92 (1H, s, H-12"), 6.37 (1H, d, J = 15.8 Hz, H-5"), 6.68 (1H, brs, H-7), 6.69 (1H, d, J = 8.0 Hz, H-10"), 6.70 (1H, dd, J = 8.0, 1.4 Hz, H-11), 6.69 (1H, d, J = 8.0 Hz, H-10), 6.74 (1H, dd, J = 8.0, 1.6 Hz, H-11"), 6.79 (1H, brs, H-7").
 ESIMS (m/z): 571 [M+ +H]
 
 Table 4: 1H & 13C NMR data of cycloadduct 2c in CDCl3 (300 MHz, δ in ppm, mult, J in Hz)
 
 Compound 4a:
 IR (KBr) nmax: 2926, 2857,1627, 1484, 1440, 1240, 1034 cm-1
 1H NMR (300 MHz, CDCl3): d ppm 0.81 & 1.35 (2H, m, H-2'), 1.29 & 1.47 (2H, m, H-4'), 1.35 (2H, m, H-2"'), 1.36 & 1.51 (1H, m, H-3'), 1.47 (2H, m, H-4"'), 1.51 (2H, m, H-3"'), 2.92 (2H, m, H-1"'), 2.99 (1H, ddd, J = 12.5, 9.7, 5.5 Hz, H-4"), 3.22 (2H, m, H-1'), 3.29 & 3.71 (2H, m, H-5'), 3.38 (1H, m, H-4"'), 3.44 (1H, dd, J = 12.1, 10.1 Hz, H-5"), 3.59 (1H, t, J = 5.3 Hz, H-5), 3.70 (1H, dq, J = 12.1, 2.1, H-2), 5.65 (1H, dd, J = 15.6, 9.5 Hz, H-3"), 5.70 (1H, dt, J = 9.9, 1.6, H-3), 5.81 (1H, d, J = 15.6 Hz, H-2"), 5.84 (1H, s, H-12"), 5.90-5.92 (2H, brs, H-12), 5.96 (1H, ddd, J = 9.2, 5.8, 2.6 Hz, H-4), 6.55 (1H, dd, J =7.9, 1.5 Hz, H-11"), 6.61 (1H, d, J = 8.2 Hz, H-10"), 6.62 (1H, d, J = 1.4 Hz, H-7"), 6.79 (1H, d, J = 7.9 Hz, H-10), 6.92 (1H, dd, J = 8.0, 1.5 Hz, H-11), 7.01 (1H, d, J = 1.5 Hz, H-7).
 ESIMS (m/z): 571 [M+ +H]
 Acknowledgements 
 The authors are thankful to Director IICT for his constant encouragement and CSIR New Delhi for providing the fellowship
 References
 
 Braun, M. Synth. Highlights 1991, 232
 Robinson, R. Chem. Soc. 1917, 762.
 Stork, G.; Burgstahler, A. W. Am. Chem. Soc. 1955, 38, 1890.
 Johnson, W. S.; Gravestock, M. B.; McCarry, B. E. Am. Chem. Soc. 1971, 93, 4332.
 Chapman, O. L.; Engel, M. R.; Springer, J. P.; Clardy, J. C. Am. Chem. Soc. 1971, 93, 6696.
 Bandaranayake, W. M.; Banfield, J. E.; Black, D. St. C. Chem. Soc., Chem Commun. 1980, 902.
 Nicolaou, K. C.; Zipkin, R. E.; Petasis, N. A. Am. Chem. Soc. 1982, 104, 5558.
 O.; Alder, K. Ann. 1928, 460, 98.
 Woodward, R. B.; Hoffmann, R. Chem. 1969, 81, 797.
 Fakui, K. Chem. Res. 1971, 4, 57.
 Houk, K. N. Chem.. Res. 1975, 8, 361.
 Houk, K. N.; Li, Y.; Evanseck, D. Angew Chem., Ed. Engl. 1992, 31, 682.
 Alder, K.; Stein, G. Chem. 1937, 50, 510.
 Fotiadu, F.; Michel, F.; Buono, G. Tetraheron Lett. 1990, 34, 4863.
 Gleiter, R.; Bohm, M. C. Pure Appl. Chem. 1983, 55, 237.
 Woodward, R. B.; Katz, T. J. Terahedron 1958, 5, 70.
 Kakushima, M. J. Chem. 1979, 57, 2564.
 Houk, K. N. Tetrahedron Lett. 1970, 30, 2621.
 Houk, K. N.; Luskus, L. J. Am. Chem. Soc. 1971, 93, 4606.
 Otto, S.; Bertoncin, F.; Engberts, J.B. F. N. Am. Chem. Soc., 1996, 118, 7702–7707.
 Wei, K.; Li, W.; Koike, K.; Chen, Y-J.; Nikaido, T. Org. Chem. 2005, 70, 1164.
 Wei, K.; Li, W.; Koike, K.; Chen, Y-J.; Nikaido, T. Lett. 2005, 7, 2833–2835.
 Rukachaisirikul, T.; Prabpai, S.; Champung, P.; Suksamrarn, A. Planta Med. 2002, 68, 850-853.
 Nagao, Y.; Seno, K.; Kawabata, K.; Miyasaka, T.; Takao, S.; Fujita, Tetrahedron Lett. 1980, 21, 841.
 Otto, S.; Boccaletti, G.; Engberts, J. B. F. N. Am. Chem. Soc. 1998, 120, 4238–4239.
 Otto, S.; Bertoncin, F.; Engberts, J. B. F. N. Am. Chem. Soc. 1996, 118, 7702–7707.
 O.; Alder, K. Ann. 1931, 490, 243.
 Woodward, R. B.; Baer, H. Am. Chem. Soc. 1948, 70, 1161.
 Breslow, R.; Rideout, D. C. Am. Chem. Soc. 1980, 102, 7816.
 Breslow, R.; Guo, T. Am. Chem. Soc. 1988, 110, 5613.
 Grieco, P.A.; Nunes, J. J.; Gaul, M. D. Am. Chem. Soc. 1990, 112, 4595.

It is important that chemical reactions initiated by electron transfer associated with electrodes can be achieved by precise control of intramolecular and intermolecular electron transfer of organic compounds, which is difficult to achieve by general chemical methods. Expectations for a new production process that positively controls the electron transfer is also expanding dramatically. Here, the solvent that dissolves the substrate for reaction, the network structure of the ionic species in the solution, and the role of coexisting substances are exactly grasped, and the total energy consumption is controlled under milder conditions. If it is possible to develop a chemical process that reduces the consumption of substances such as reaction reagents to the utmost while significantly suppressing the above, it is expected that structural conversion of chemical substances based on the electron transfer process can be realized. This means that advanced control of the formation, stabilization, and subsequent reactions of active open-shell molecules opens the door to new chemical reactions that reduce excess reagent and energy consumption. There is a possibility that the atom economy will be dramatically enhanced by the electron transfer reaction process for the reagents that need to be charged. This achieves a chemical reaction that is regarded as "Electrons as Reagents", and it will be a core technology that will bring about innovation in the chemical substance manufacturing method that is currently produced with the production of a large amounts of unnecessary substances and energy consumption. Research achievements: In such a background, K. Chiba pioneered original organic electrolytic reactions based on the research activities on chemical synthesis of biologically active natural compounds, and achieved various carbon skeleton formation, chemical synthesis of useful substances and biologically active natural substances. One of the notable results is the electrolytic synthesis reaction method using a unique electrolyte solution composed of lithium perchlorate / nitromethane. It was shown that the cation species generated by electrode electron transfer using this electrolyte solution are stabilized and can be applied to the formation of a wide variety of intermolecular carbon-carbon bonds. That is, numerous electrode process-triggered reactions such as varied (hetero)Diels-Alder reactions, [3+2], and [2+2] cycloaddition reactions have been achieved. In addition, the olefin metathesis without transition metal catalysis was successful for the first time. The importance of the role of the electrolyte solution in the organic electrolysis reaction was widely shown. The elucidation of these reaction mechanisms and new findings on the action of the reaction field have contributed to the rapid development of the field in recent years by utilizing and enhancing the functions of various electrolyte solutions. In addition, the application of the new organic electrolysis method has widely developed chemical synthesis methods for natural and non-natural peptides, artificial nucleic acids, etc. It is noteworthy that it was successful in electrolytic synthesis of various aza-nucleosides by utilizing the cation species under the stabilizing action of the lithium perchlorate / nitromethane electrolyte solution. This basic skeleton paves the way for mass synthesis of nucleic acid derivatives, which are promising as therapeutic drug for covid-19. Furthermore, K. Chiba achieved organic electrolytic reactions that mimic the electron transfer process in the living body. Inspired by the bio-mimic chemical reaction system, he proposed a chemical process based on biphasic solutions. The key technology is the introduction of a solution system that combines a highly polar electrolyte solution and a hydrophobic organic solvent. By controlling the temperature, phase-fusion and phase-separation can be repeated, so that the product, for example, can be taken out from the reaction system while reusing the electrolyte solution. By forming reverse micelles in a hydrophobic solvent, a continuous reaction system can be constructed, which has led to the proposal of an important method for industrial application of electrolytic reactions and of multi-step medium-size molecule syntheses reducing environmental load. Outlook for the future: We must achieve a more efficient cycle of material, food and energy to support the world's population of 9 billion in the near future. For that purpose, it is extremely important to pay attention to and apply the functions of electrons involved in the production and decomposition of all chemical substances, including the elucidation and utilization of biological functions. The key technology of controlling electron transfer is indispensable for achieving a smart green society boosting a better Anthropocene.

Abstract Silver nanoparticles (Ag NPs) system capable of exhibiting different particle size at different temperature was developed, which depended on the extent of Diels–Alder (DA) reaction of bismaleimide with furan. Thus, Ag NPs were functionalized on the surface by a furyl-substituted carbene through an insertion reaction. Subsequent reversible DA crosslinking achieved a controlled aggregation with different particle size, which gives a series of different antibacterial activity. These Ag NPs were characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectroscopy (XPS), and Nanoparticle Size Analyzer. The aggregation of the Ag NPs could be reliably adjusted by varying the temperature of DA/reverse-DA reaction. The antibacterial activity was assessed using the inhibition zone method against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which decreased first and then increased in agreement with the size evolution of Ag NPs. This approach opens a new horizon for the carbene chemistry to modify silver nanoparticles with variable size and give controlled antibacterial activity.

AbstractA fruitful debate took place recently in literature, discussing the enhanced Diels–Alder reactivity of tropone derivatives for which the carbonyl polarity was reversed by means of umpolung. Karas et al. sustained that the umpolung increases the antiaromatic character of the ring, affecting the highest occupied molecular orbital (HOMO)/least unoccupied molecular orbital (LUMO) energies, speeding up the reaction. Tiekink et al. challenged this interpretation by sustaining that the asynchronicity of the reaction mechanisms, rather than orbital energy perturbation, was the main responsible for the smaller reaction barriers. We shed light on this dispute by computing full interaction quantum atom (IQA) and quantum theory of atoms in molecules (QTAIM) analyses over complete intrinsic reaction coordinate (IRC) paths for the Diels–Alder reaction of tropone and its umpolung derivatives, using the same systems studied by Karas et al. and Tiekink et al. Our results confirm that the asynchronicity is indeed very high for those reactions with smaller reaction barriers and offer an atom‐by‐atom and bond‐by‐bond analysis of the entire IRC pathways. Even though asynchronicity and lower reactions barriers seem to be related, antiaromaticity and lower barriers are related as well, but discussing both these interpretations does not necessarily require arguments on HOMO/LUMO energies to be invoked.

AbstractFuran heterocyclic compounds derived from renewable sources are popular versatile candidates for the production of multifunctional macromolecular materials. These compounds are also used as hydrophobilization monomers for reversible polyadducts or as versatile building blocks in Diels‐Alder reactions. In the present study, an efficient approach to chemoselective acylation of furfurylamine with a series of non‐preactivated monocarboxylic or dicarboxylic long‐chain fatty acids and some of their functionalized derivatives has been achieved via catalytic direct amidation in reversed micellar medium. A convenient and environmentally friendly method has been developed for furfurylamides via a dehydrative coupling reaction. For this purpose, a new cationic Brønsted‐type sulfonic acid catalyst containing a hexadecyl alkyl chain was synthesized and fully characterized. The present catalytic reaction produced the respective N‐furfurylamides materials in good to excellent yields. This study also confirms that the direct amidation of carboxylic acids with selected amine compounds can be successfully catalyzed by Brønsted acids. Its simplicity and high atom economy are the main advantages of this method.

Chiral catalysts for asymmetric catalysis represent a crucial research focus in chemistry and materials science. However, a few cases about chiral‐dependent photocatalysts primarily focus on plasmonic noble metals. Particularly, developing chiral nano‐catalysts that can be driven by mechanical energy remains in the blank stage. Herein, organic polymer‐based enantiomers, chiral polar polyimide (PI) microspheric nano‐assembly are synthesized as novel bifunctional catalysts for asymmetric photocatalysis and piezocatalysis. The PI catalyst enantiomers present enantioselectivity towards left‐ and right‐circularly polarized light, demonstrating chiral‐dependent H2O2 photoproduction. Interestingly, enantioselectivity of the catalyst reverses under irradiation of different bands, presenting tunability in the interaction between chiral catalysts and circularly polarized light. For the first time, enantioselective piezocatalytic behavior is demonstrated by the chiral polar PI catalysts. They show remarkable chiral preference for asymmetric Diels‐Alder reaction and enantioselective conversion of tyrosine substrates under ultrasonic vibration. The findings provide a new perspective into exploring metal‐free chiral catalysts and their asymmetric catalysis applications across multiple energy forms.

Chiral catalysts for asymmetric catalysis represent a crucial research focus in chemistry and materials science. However, a few cases about chiral‐dependent photocatalysts primarily focus on plasmonic noble metals. Particularly, developing chiral nano‐catalysts that can be driven by mechanical energy remains in the blank stage. Herein, organic polymer‐based enantiomers, chiral polar polyimide (PI) microspheric nano‐assembly are synthesized as novel bifunctional catalysts for asymmetric photocatalysis and piezocatalysis. The PI catalyst enantiomers present enantioselectivity towards left‐ and right‐circularly polarized light, demonstrating chiral‐dependent H2O2 photoproduction. Interestingly, enantioselectivity of the catalyst reverses under irradiation of different bands, presenting tunability in the interaction between chiral catalysts and circularly polarized light. For the first time, enantioselective piezocatalytic behavior is demonstrated by the chiral polar PI catalysts. They show remarkable chiral preference for asymmetric Diels‐Alder reaction and enantioselective conversion of tyrosine substrates under ultrasonic vibration. The findings provide a new perspective into exploring metal‐free chiral catalysts and their asymmetric catalysis applications across multiple energy forms.

RationaleThe mechanism underlying dopant‐assisted atmospheric pressure photoionization's (APPI) formation of ions is unclear and still under debate for many chemical classes. In this study, we reexamined the gas‐phase reaction mechanisms responsible for the generation of [M–H]+ precursor ions, resulting from the loss of a single hydrogen atom, in a series of N‐alkyl‐substituted thieno[3,4‐c]‐pyrrole‐4,6‐dione (TPD) derivatives.MethodsAtmospheric pressure photoionization combined with higher order MS/MSn using high‐resolution mass spectrometry (APPI‐HR‐CID‐MSn) and electronic structure calculations using density functional theory were used to determine the chemical structure of observed [M–H]+ ions.ResultsAs a result, the higher order MSn (n = 3) experiments revealed a reversed Diels–Alder fragmentation mechanism, leading to a common fragment ion at m/z 322 from the studied [M1–5–H]+ ion species. In addition, the calculation for two chemical structure models (N‐alkyl‐TPD1 and N‐alkyl‐TPD5) showed that the fragment structure, resulting from the removal of the hydrogen atom connected to the third carbon atom of the N‐alkyl side chain, has a more stable cyclic form compared with the linear one.ConclusionsThe proposed chemical structure of the N‐alkyl TPD ion species, following the loss of a single hydrogen atom, was revealed during APPI‐HR‐CID‐MSn (n = 3) experiments on the [M–H]+ species. Hydrogen radical (H•) abstraction from the alkyl side chain (e.g., hexyl, heptyl, octyl, 2‐ethylhexyl, and nonyl) triggered a rearrangement in the radical cation structure of the N‐alkyl‐TPD derivatives, initiating cyclization and forming a six‐membered ring that connects the oxygen atom to the third carbon atom in the alkyl chain. In addition, theoretical calculations supported the APPI‐HR‐CID‐MSn (n = 3) experiments by demonstrating that the proposed chemical structure, resulting from the intramolecular cyclization of the N‐alkyl‐TPD ion species, was stable in the presence of chlorobenzene. These findings will aid the structural determination and elucidation of molecules with similar core structures.