Unprecedented Regio- and Stereoselective Synthesis of Pyrene-Grafted Dispiro[indoline-3,2'-pyrrolidine-3',3″-indolines]: Expedient Experimental and Theoretical Insights into Polar [3 + 2] Cycloaddition.

A series of dispiro[indoline-3,2'-pyrrolidine-3',3″-indolines] was synthesized via a multicomponent polar [3 + 2] cycloaddition (32CA) reaction of isatin derivatives, sarcosine and (E)-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-one derivatives. The regio- and stereochemistries of the cycloadducts were established on the basis of one-dimensional (1D) (1H-, 13C-, 13C-CRAPT NMR) and two-dimensional (2D) homonuclear and heteronuclear correlation NMR spectrometry experiments (1H-1H gDQFCOSY, 13C-1H-HSQCAD, 13C-1H-HMBCAD, 1H-1H-ROESYAD). The molecular mechanism and regio- and stereoselectivities of the cycloaddition (CA) reaction have been investigated utilizing a density functional theory (DFT) method and were thoroughly explained based on the transition-state stabilities and global/local electrophilicity/nucleophilicity reactivity indices of the reactants.

Exploiting a multicomponent domino reaction strategy for the tailoring of versatile environmentally sensitive fluorophore-based nicotinonitriles incorporating pyrene and fluorene moieties.

A simplistic and highly effective protocol for the synthesis of a new class of poly-functionalized innovative nicotinonitriles incorporating pyrene and/or fluorene moieties has been developed through the domino four-component condensation reaction of 1-(pyren-1-yl)ethanone/1-(9H-fluoren-2-yl)ethanone, numerous aromatic aldehydes, and 3-oxo-3-(pyren-1-yl)propanenitrile/3-(9H-fluoren-2-yl)-3-oxopropanenitrile and ammonium acetate in acetic acid as a reaction medium. The advantages of this approach are the short reaction time, excellent yield, and the easy experimental workup that affords substrate diversity and operative competence under metal-free reaction conditions for the formation of C-C and C-N bonds. The substituent effects on the photophysical property-based absorption and the emission of the synthesized compounds in dichloromethane have been well-investigated. Strong absorption quenching of around 100 nm was observed when substitution of the benzene ring at the C4-position of the pyridine moiety occurred with an electron-donating (-N(CH3)2) group. All of the newly synthesized nicotinonitrile derivatives showed strong blue-green fluorescence emission with maxima in the range between 420-630 nm. These highly pronounced emission spectra will help this family of compounds to find application in many areas and the field of materials science.

Facile access to regio- and stereoselective synthesis of highly functionalized spiro[indoline-3,2'-pyrrolidines] incorporating a pyrene moiety: experimental, photophysical and theoretical approach.

The regio- and stereochemical polar [3 + 2] cycloaddition of azomethine ylides, which were generated in situ by the reaction of isatin and sarcosine or benzylamine, with (E)-3-aryl-1-(pyren-1-yl)prop-2-en-1-ones as dipolarophiles, was studied using experimental and theoretical methods. The chemical structures and relative configurations of all products have been fully established by 1D and 2D homonuclear and heteronuclear correlation NMR spectrometry. The effects of the electronic and steric factors of the reactions were discussed. The photophysical properties of the synthesized spiro[indoline-3,2'-pyrrolidin]-2-ones and 5'-phenyl-spiro[indoline-3,2'-pyrrolidin]-2-ones were studied. The mechanism of the reactions was investigated using global and local reactivity indices and frontier molecular orbital (FMO) analysis at the B3LYP/6-31G level of theory. The relationship between the electrophilicity index ω of the dipolarophiles and the Hammett constant σ p has been studied. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in the para-position of the dipolarophiles.

Electronic and solvent effects on kinetics of SNAr substitution reactions of substituted anilines with 2,6-bis(trifluoromethanesulfonyl)-4-nitroanisole in MeOH-Me2SO mixtures of varying composition: one reaction with two mechanistic pathways.

ABSTRACT: The kinetics and mechanism of the aromatic nucleophilic substitution reactions of 2,6-bis(trifluoromethanesulfonyl)-4-nitroanisole with para-X-substituted anilines (X = OH, OMe, Me, H, F, I, Cl) were studied in MeOH-Me2SO mixtures and pure Me2SO at 25.0 °C. The second-order rate coefficients depend on the substitutent in aniline and give good Hammett and Brønsted correlations; a polar SNAr reaction is proposed for the reaction in different MeOH-Me2SO mixtures. The measured rate coefficients of the reaction demonstrated dramatic variations for aniline donor with the increasing dimethyl sulfoxide composition in MeOH-Me2SO mixtures. In this case, the Hammett and Brønsted plots are biphasic and concave upwards with a break point at 4-methylaniline. These results indicate a change in mechanism from the polar (SNAr) for less basic nucleophiles (X = 4-Cl, 4-I, 4-F, and H) to the single electron transfer (SET) for more basic nucleophiles (X = 4-OH, 4-OMe and 4-Me). The changes of the structure of the transitions states with substituents and solvent are in accordance with the results of kinetics studies. The solvation model described is well supported by the solvatochromism exhibited by aniline in the solvent mixture under investigation. These results provide an ideal framework for understanding the paramount importance of the specific molecular structure of solvent molecules in determining chemical reactivity versus solvent effects.

The Diels-Alder reaction of 4,6-dinitrobenzofuroxan with 1-trimethylsilyloxybuta-1,3-diene: a case example of a stepwise cycloaddition.

The reaction of 4,6-dinitrobenzofuroxan (DNBF) with 1-trimethylsilyloxybuta-1,3-diene (8) is shown to afford a mixture of [2+4] diastereomeric cycloadducts (10, 11) through stepwise addition-cyclization pathways. Zwitterionic intermediate sigma-adduct 9, which is involved in the processes, has been successfully characterized by (1)H and (13)C NMR spectroscopy and UV/visible spectrophotometry in acetonitrile. A kinetic study has been carried out in this solvent that revealed that the rate of formation of 9 nicely fits the three-parameter equation log k=s(E+N) developed by Mayr to describe the feasibility of nucleophile-electrophile combinations. This significantly adds to the NMR spectroscopic evidence that the overall cycloadditions take place through a stepwise mechanism. The reaction has also been studied in dichloromethane and toluene. In these less polar solvents, the stability of 9 is not sufficient to allow direct characterization by spectroscopic methods, but a kinetic investigation supports the view that stepwise processes are still operating. An informative comparison of our reaction with previous interactions firmly identified as prototype stepwise cycloadditions is made on the basis of the global electrophilicity index, omega, defined by Parr within the density functional theory, and highlighted by Domingo et al. as a powerful tool for understanding Diels-Alder reactions.

The ambident reactivity of 2,4,6-tris(trifluoromethanesulfonyl)anisole in methanol: using the SO2CF3 group as a tool to reach the superelectrophilic dimension in sigma-complexation processes.

The kinetics of sigma complexation of 2,4,6-tris(trifluoromethanesulfonyl)anisole (7 d) have been investigated over a large pH range of 2-13.70 at T = 20 degrees C in methanol. Two competitive processes associated with the initial addition of MeO(-) at the unsubstituted 3-position of 7 d to give a 1,3-dimethoxy adduct (9 d-Me) and a subsequent and slow conversion of this species into a 1,1-dimethoxy isomer (8 d-Me) have been identified. Both adducts 8 d-Me and 9 d-Me are 10(5)-10(6) times more stable than the related adducts 8 a-Me and 9 a-Me of 2,4,6-trinitroanisole (7 a), a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high stability of 8 d-Me and 9 d-Me is shown to derive from greater rates of formation and lower rates of decomposition than previously determined for 8 a-Me and 9 a-Me, thereby emphasising the especially high activation of a benzene ring by SO(2)CF(3) group(s). Analysis of the collected rate and equilibrium data for sigma complexation in the anisole series 2,4,6-tris(SO(2)CF(3))-, 2,6-bis(SO(2)CF(3))-4-nitro-, 4-SO(2)CF(3)-2,6-dinitro- and 2,4,6-trinitro- supports the idea that the especially high capacity of resonance stabilisation of the negative charge of the adducts through an F(pi)-type (as defined in ref. 49) polarisation effect is a major factor that accounts for the strong activation provided by SO(2)CF(3) groups. A most significant result is the finding that the 1,1-dimethoxy adduct 8 d-Me is by far the most stable benzene sigma adduct so far reported. With a pK(a)(MeOH) value of 7.32, this adduct is formed exclusively through methanol addition up to pH approximately 10. This is consistent with the location of 7 d in the superelectrophilic region defined by pK(a)(MeOH) < or = 9.5-10.5. For comparison, the solvent contribution is negligible in the formation of the 1,3-isomer 9 d-Me, the pK(a)(MeOH) (10.59) of which is situated on the upper limit of the boundary. Taking advantage of the simple relationship linking pK(a) values for sigma complexation in methanol and water, a ranking of the triflone 7 d on the general thermodynamic scale constructed for Meisenheimer electrophiles in water is informative. An approximate calibration on the electrophilicity scale kinetically derived by Mayr et al. has also been made.

Electrophilicity of aromatic triflones in sigma-complexation processes.

The kinetics of sigma-complexation of 2,6-bis(trifluoromethanesulfonyl)-4-nitroanisole (4) have been investigated over a large pH range of 2-15.68 in methanol. Two competitive processes have been identified with the initial addition of MeO(-) at the unsubstituted 3-position of 4 to give a 1,3-dimethoxy adduct (4b-Me) and a subsequent and slow conversion of this species into the 1,1-dimethoxy isomer (4a-Me). Both 4a-Me and 4b-Me are more stable than the related adducts of 2,6-dinitro-4-trifluromethanesulfonylanisole, i.e.5a-Me and 5b-Me, and 2,4,6-trinitroanisole, i.e.6a-Me and 6b-Me, the latter compound being a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high thermodynamic stability of 4a-Me (pK(a) = 10.48) and 4b-Me (pK(a) = 12.23) relative to 5a-Me (pK(a) = 10.68) and 6a-Me (pK(a) = 12.56) or 5b-Me (pK(a) = 15.38) and 6b-Me (pK(a) = 16.46), is shown to derive from an especially high capacity of a para or an ortho SO(2)CF(3) group to stabilize a negative charge through Fpi-type polarization effects. From the kinetic data, it appears that the contribution of a methanol pathway to the formation of 4a-Me is much weaker than that found to operate in the formation of the 1,1-complex 5a-Me of 2,6-dinitro-4-trifluromethanesulfonylanisole, the experimental evidence suggesting that the reactivity of 4 and 5 is located just beyond the region defining the boundary between super- and normal-electrophilicity in methanol. Comparison of our results with available literature data show that this boundary corresponds to a pK(MeOH)(a) value of approximately 10, in agreement with our previous finding of a very effective solvent contribution to the sigma-complexation of 1,3,5-tris(trifluoromethanesulfonyl)benzene (13; pK(MeOH)(a) = 9.12) in methanol. Taking advantage of our observation that pK(MeOH)(a) and pK(H(2)O)(a) values for sigma-complexation at unsubstituted ring positions are related by a nice linear correlation, an approximate ranking of the electrophilicity of our aromatic triflones on the E scale developed by Mayr (Acc. Chem. Res. 2003, 36, 66) can be made.