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The first detailed thermodynamic analysis in terms of the driving forces for ach basic step for the nitric oxide (NO)-initiated reaction with 3,6-dibromocarbazolide is presented. It is shown that an electrophilic combination of NO with 3,6-dibromocarbazolide to form the incipient radical anion, followed by electron transfer from the latter to NO, represents the most feasible mechanism. Electron transfer from the electron-rich species to NO may be incorporated when the substrate is a better electron-providing species.

Research was conducted to examine the role of adjacent onium cations and remote substituents on the H-A+ bond equilibrium acidities in dimethyl sulfoxide solution. The study is an extension of previous investigation on ylide thermodynamic stability scale and its implication for the importance of resonance effect on ylide stabilities. Results suggest that part of the stabilization in the phosphonium and sulfonium ylide cases arises from the backbonding stabilization involving the o* and/or 3d orbital participation.

Bond dissociation energies of the acidic C-H bonds in 13 alpha-substituted 9-mehtylanthracenes and 11 10-substituted methylanthracenes. This included equilibium acidity (pKHA), reduction potential Ere(HA), oxidation potential Eox(HA), and oxidation potential of conjugate anions Eox(A-) in dimethyl sulfoxide solution. Equilibrium acidities were linearly correlated with Hammettsigma negative constants. Combinations of equilibrium acidities were used to determine homolytic bond dissociation energies.

Bond dissociation energies and hydronium ion concentrations at equilibrium of benzylic carbon to hydrogen bonds in dimethyl sulfoxide are presented. Nineteen triphenylmethanes, three dihydroanthracenes and nine xanthenes were used in the experiment. The resonance effect due to the solvation of a substituent induced a conformational alteration to allow for conjugative overlap of the anion and the substituents. The effect of substituents far from the carbanion was found to be negligible.

Alpha-sulfonium groups are radical stabilizing rather than radical destabilizing, as gleaned from theoretical calculations in an examination of the radical substituent effects of the alpha-sulfonium groups. Results showed that the radical-stabilizing effects of the alpha-dialkylsulfonium groups are smaller and with larger steric hindrance than those for the alpha-RS groups. They were also found to be associated with the free lone pair electrons of the sulfur atom in the sulfonium groups. The latter were found to be able to form a two-center three-electron bond with the unpaired electron of the radical.

Examines equilibrium acidities and homolytic bond dissociation enthalpies of the acidic C-H bonds in As-substituted triphenylarsonium and related cations. Examination of the effects of a-triphenylarsonium groups on the equilibrium acidities; Results and discussion of the findings.

Presents information pertaining to the formal hydride transfer reactions regarding the reduced nicotinamide adenine dinucleotide (NADH) models, referencing to various cations and quinones. Possibility of a hybrid mechanism; How reduction potentials were obtained;Evaluation of the bond dissociation free energy of the 9-C-H bond in N-methylacridinium ion (AcrH+).

Studies the free energy hydride affinities of quinones in dimethyl sulfoxide solution. Use of thermochemical cycle; Determination of the pKa of hydroquinone monoanions; Observation of the values of deltaGhydride(Q)DMSO.

The metal-free catalytic C-F bond activation of polyfluoroarenes was achieved with diazaphospholene as the catalyst and phenylsilane as the terminal reductant. Density functional theory calculations suggested a concerted nucleophilic aromatic substitution mechanism.

The equilibrium acidities for several series of structural and electronic different organic acids were measured in 3-pyrrolidinium-based aprotic and protic ionic liquid (IL) analogues, that is, [Bmpy][NTf 2 ], [BpyH][NTf 2 ], and [PyH 2 ][NTf 2 ], by the UV-Vis method. The acidities of neutral acids are found to be much stronger in the protic ILs (PILs) than aprotic ILs (AILs), and the acidifying effect in the two PILs roughly increases proportionally to the number of protons in the cation of the PIL. On the other hand, interestingly, the cationic N + -H acids exhibit similar acidities in [Bmpy][NTf 2 ] and [BpyH][NTf 2 ] but much weaker than those in [PyH 2 ][NTf 2 ]. The Hammett ρ values for the acidic dissociation of para-substituted benzoic acids in two PILs are about the same as that in water (1.00) but significantly smaller than that in the AIL [Bmpy][NTf 2 ] (2.66). The correlations between the acidities in the PILs and water show double-linear relationships with different slopes and intercepts for the neutral and cationic acids. These, together with previous observations in the PILs [DBUH][OTf] (DBU = 1,5-diazabicyclo(5.4.0)-5-undecene) and EAN (ethylammonium nitrate), clearly indicate that the structure of the cation plays a subtle but a crucial role on sensing the electronic nature of solutes and strongly affects the solvation behaviors of PILs.

Green and efficient C-C bond cleavage/cyanoalkylation of quinoxalin-2(1 H)-ones and other heteroarenes under visible light or sunlight irradiation is described. The reaction proceeds under mild conditions at room temperature without transition-metal catalysts and extra bases. Notably, the products enable facile transformations to various significant organic compounds.

The merger of the common photoredox catalyst Ru(bpy) 3 Cl 2 with an imidazolidinone organocatalyst by MacMillan et al. has enabled a series of highly enantioselective α-functionalizations of aldehydes, a landmark discovery in photoredox organocatalysis. Herein, we present the theoretical investigation into the origin of enantioselectivity in asymmetric radical additions to the MacMillan imidazolidinone enamines, the key stereocontrolling step in photoredox organocatalysis of asymmetric α-functionalizations of aldehydes. The calculations reveal a hidden but crucial role of E-cis enamine in enantiocontrol. The enantioselectivity in the radical additions is mainly determined by steric effects. A model based on the pseudo C 2 -symmetric arrangement of the methyl and tert-butyl moieties on the catalyst is proposed. This rationalizes the stereoselective outcome of these reactions and provides a good model to understand MacMillan's imidazolidinone/photoredox dual catalysis. The insights obtained from this study should be valuable in future efforts toward the design and development of new enantioselective catalytic radical reactions.

A chiral squaramide catalyzed approach constructing spiro-3,4-dihydrocoumarin motif by the enantioselective 1,6-addition/acetalization reactions of 1-oxotetralin-2-carbaldehydes and ortho-hydroxyphenyl-substituted para-quinone methides followed by an oxidation was developed. The reactions proceeded smoothly with a wide range of p-QMs and 1-oxotetralin-2-carbaldehydes to generate corresponding products in high yields with excellent diastereoselectivities (>19:1 dr) and enantioselectivities (up to 99% ee).

An acidity scale of triazolium-based N-heterocyclic carbene precursors was established by measuring 25 compounds' (10a-15b) equilibrium acidities in dimethyl sulfoxide (DMSO) solution using overlapping indicator method. The pK a values ranged from 12.08 to 15.5, responding not only to the N-aryl motif, but also to the core structure. Excellent correlation was observed between the pK a values and the Hammett substituent constants (σ p ).

The sources of asymmetric induction in the photoinduced phase-transfer-catalytic perfluoroalkylation of β-ketoesters were interpreted by density functional theory calculations. The calculations indicated that multiple hydrogen-bonding interactions mode rather than π-π stacking interactions model better described the transition structure of the reaction. The quantitative estimation of these noncovalent interactions within the key transition states identified that the O-H···O and specific C-H···O hydrogen bonds play key roles for the stereocontrol.

The recent recognition of the novel application of a few traditional electrophilic trifluoromethylthiolating reagents as SCF 3 radical sources offers a remarkable new opportunity for the development of radical trifluoromethylthiolation reactions. Herein, the first trifluoromethylthio radical donating ability (Tt • DA) scale of electrophilic SCF 3 -transfer reagents has been developed. This scale is based on Y-SCF 3 bond dissociation energies, which were obtained by density functional calculations (M06-2X). Single electron transfer is revealed to exhibit a substantial Y-SCF 3 bond-weakening effect, thus significantly facilitating the SCF 3 radical ( • SCF 3 ) release. The results may aid in future novel radical SCF 3 -transfer reagent design and new reaction development.

A series of novel N-tert-butyl sulfinyl squaramide receptors have been designed and synthesized. Their interactions with a range of inorganic anions were studied in solution by 1 H NMR spectroscopy. This new type of squaramide displayed better anion-binding abilities over conventional diphenyl squaramides. The single crystal analysis and DFT calulations implied the role of the tert-butyl C-H protons in binding Cl - . The energies of C-H···Cl - interactions were estimated to be 1.4-1.6 kcal/mol in solution.

An efficient asymmetric vinylogous Michael addition of 3-alkylidene oxindoles and enals has been achieved using a chiral TBS-protected diphenylprolinol catalyst. The γ-substituted alkylidene oxindoles obtained bear a chiral tertiary center and are afforded in moderate to good yields and good to excellent enantioselectivities.

A metal-free, visible-light-induced photocatalytic procedure for decarboxylative alkynylation of carboxylic acids was reported. With 9,10-dicyanoanthracene as the photoredox catalyst, the reaction covered a broad scope of α-amino acids, α-oxo acids, and α-keto acids with blue LED irradiation at room temperature under an atmosphere of argon, delivering alkynyl products in moderate to excellent yields. Natural sun light also promoted this alkynylation strategy. This work represents the first example of an organophotocatalytic method for decarboxylative alkynylation of carboxylic acids.

Absolute pK a s of 25 sulfonamides in four ionic liquids (ILs) were measured spectroscopically with high precision and subsequently compared with those in conventional molecular solvents. It is found that the acidity order of these sulfonamides is as follows: in water > in DMSO > in ILs > in acetonitrile (ACN). The well-known solvent polarity index ε fails to explain the observed stronger bond-weakening effect of ILs in comparison to that of ACN, whose ε value is much greater. In addition, the regression analyses show that the pK a s of sulfonamides determined in ILs linearly correlate with these in molecular solvents of distinct properties, but with various slopes. A rationale and related discussion on the effect of solvation in ILs are presented.

The mechanism and origin of the unexpected chemoselectivity in fluorocyclization of o-styryl benzamide with a cyclic hypervalent fluoroiodane reagent were explored with DFT calculations. The calculations suggested an alternative mechanism that is broadly similar to, but also critically different from, the previously proposed mechanism for the formation of an unexpected structurally novel seven-membered 4-fluoro-1,3-benzoxazepine. The amide group of o-styryl benzamide was revealed to be crucial for activating the fluoroiodane reagent and facilitating C-F bond formation. In contrast to the popular electrophilic N-F reagent Selectfluor, the F atom in the fluoroiodane reagent is nucleophilic, and the I(III) atom is the most electrophilic site, thus inducing a completely different reactivity pattern. The insights reported here will be valuable for the further development of new reactions based on the hypervalent fluoroiodane reagent.

Quantitative knowledge of the fluorinating strength of electrophilic N-F reagents is of crucial importance for rational design and optimization of novel reagents and new reactions. Herein, we report the first systematic computation of fluorinating potentials of 130 electrophilic N-F reagents in two commonly used solvents dichloromethane and acetonitrile in terms of the N-F bond heterolysis energies as expressed by the fluorine plus detachment (FPD) values. The calculated FPD scales of 130 N-F reagents cover a range from 112.3 to 290.4 kcal mol(-1) and 110.9 to 278.4 kcal mol(-1) in dichloromethane and acetonitrile, respectively. This comprehensive FPD database provides a valuable quantitative guide for studying the influence of structural variation on the fluorinating strength of the N-F reagents, opening a door to the rational design of novel reagents with appropriate fluorinating strength for specific purposes. It is demonstrated that the FPD values can reproduce the reactivity order for electrophilic N-F reagents better than other parameters.

This work established an energetic guide for estimating the trifluoromethyl cation-donating abilities (TC(+)DA) of electrophilic trifluoromethylating reagents through computing X-CF3 bond (X = O, S, Se, Te, and I) heterolytic dissociation enthalpies. TC(+)DA values for a wide range of popular reagents were derived on the basis of density functional calculations (M06-2X). A good correspondence has been identified between the computed TC(+)DA values and the experimentally observed relative trifluoromethylating capabilities of the reagents. Substituent effects hold good linear free energy relationships on the TC(+)DAs of the most widely used reagents including Umemoto reagent, Yagupolskii-Umemoto reagent, and Togni reagents, which allow their trifluoromethylating capabilities to be rationally tuned by substituents and thus extend their synthetic utility. All the information disclosed in this work would contribute to future rational exploration of the electrophilic trifluoromethylation chemistry.

In contrast to the great success of computational methodologies in molecular solvents, effective and accurate calculation of the fundamental bond energetic properties in ionic liquids (ILs) is essentially absent. This is largely due to the unusual complexity of handling solvation quantities of ILs and the lack of precisely determined bond parameters to serve as the authentic benchmark to calibrate the modeling methodology. Herein, we report the first accurate calculations of absolute pK(a) values in a commonly used IL, [Bmim][NTf2], with the carefully developed "ion-biased" cluster-continuum model. Experimental pK(a) values of benzoic acids and benzenethiols in [Bmim][NTf2] were reproduced with mean unsigned errors of only 0.3 and 0.5 pK(a) units, respectively, which enables theoretical approaches with a suitable strategy as a powerful tool to handle complicated problems in ILs and to eventually realize the rational design of the IL chemistry.

The equilibrium basicities of 21 frequently used amines in two room-temperature ionic liquids (RTILs) were measured precisely. The standard deviation was much superior to that sparsely reported elsewhere. The data comparisons revealed that amines are stronger bases in ionic ligquids than in DMSO and water but weaker base than in acetonitrile (AN). Interestingly, regression analyses demonstrate that the basicity scales obtained in two RTILs correlate well with that in AN but not with those in water and DMSO.

A highly enantioselective [4+2] annulation with respect to allenoates and 3-olefinic oxindoles catalyzed by Lewis base was reported, which proved to be an efficient way to synthesize chiral dihydropyran-fused indoles. The cycloaddition products were generally obtained in high yields (up to 98%) with very good enantioselectivities (up to 94% enantiomeric excess).

The pK(a) values of a series of chiral Brønsted acids, including N-triflylphosphoramides, bis(sulfonyl)imides, bis(sulfuryl)imides, dicarboxylic acids, sulfonic acids, and N-phosphinyl phosphoramides, were predicted by using the SMD/M06-2x/6-311++G(2df,2p)//B3LYP/6-31+G(d) method in DMSO. The results revealed that the calculated pKa values ranged from -9.06 to 12.18 for different types of acids. The influence of acidic strength on reactivity and stereoselectivity was discussed using the calculated acidity data. Given that the choice of catalyst with appropriate acidity is the primary condition, several new catalyst candidates were designed by calculating corresponding pK(a) values of parent acids.

The pKa shifts of proline induced by a family of hydrogen-bond-donating cocatalysts were computationally evaluated with the M06-2x/6-311++G(2df, 2p)//B3LYP/6-31+G(d)(SMD) method. The calculation predicted that the acidity of proline could be increased by more than 9 pKa units in nonpolar solvents (n-hexane and toluene) when it assembles with hydrogen-bond-donating cocatalysts, which would contribute to the dramatically enhanced catalytic properties. For hydrogen-bond-donating cocatalysts, their relative abilities to induce the pKa shifts of proline in the gas phase and common organic solvents were established and were found to be well-correlated with their acidities. The results may aid in future development of modularly designed supramolecular catalysis--the assembly of catalyst species by harnessing multiple weak intermolecular interactions.

Equilibrium acidity (pKa) scales of 15 substituted benzoic acids in four room temperature ionic liquids (RTILs), BmimOTf, BmimNTf2, BmpyNTf2, and Bm2imNTf2, were established under standard conditions using a modified indicator overlapping method. The effect of homo hydrogen bonding on equilibrium acidity was calibrated, and the derived pKa values were evidenced to be free from ion-paring complication. Regression analyses demonstrated that all of the pKa scales obtained in four RTILs are linearly correlated to each other with an R value better than 0.996. These scales are also correlated well with the pKa values in DMSO and with the corresponding gas-phase acidities with regression coefficients of 0.993 and 0.992, respectively. In addition, both the cation and anion of the ionic liquids were found to play a role in affecting the acidity of carboxylic acid.

The pKa values of 41 chiral phosphoric acid-family catalysts in DMSO were predicted using the SMD/M06-2x/6-311++G(2df,2p)//B3LYP/6-31+G(d) method for the first time. The study showed that the calculated pKa's range from -4.23 to 6.16 for absolute pKa values and from -4.21 to 6.38 for relative pKa values. Excellent agreement between the calculated and experimental pKa's was achieved for the few available cases (to a precision of around 0.4 pKa unit), indicating that this strategy may be suitable for calculating highly accurate pKa's. A good linear correlation between the pKa's for 3 and 3' disubstituted phenyl BINOL phosphoric acids and the Hammett constants was obtained. The relationship between the acidities of phosphoric acid catalysts and their reaction activity and selectivity was also discussed. Knowledge of the pKa values of phosphoric acids should be of great value for the understanding of chiral Brønsted acid-catalyzed reactions and may aid in future catalyst design.

We describe herein a viable binary acid strategy for the catalytic Nazarov reaction of aryl vinyl ketones. Simply combining a Lewis acid and a Brønsted acid led to a dramatic enhancement of the catalytic activity in the Nazarov reaction of aryl vinyl β-ketoesters. The obtained optimal binary acid catalyst In(OTf)(3)/diphenyl phosphoric acid (DPP) can be applied to a range of aryl vinyl ketones with good activity. A trend of reactivity has also been summarized on the basis of mapping of the substituents.

Energetics of bond dissociation, especially the R-H bond heterolysis free energy (pK(a)), has played a central role in promoting chemistry to become a rational science. Despite the oceans of acidity studies in the literature, the current knowledge is limited to that in the classical molecular solvents and is unable to be extended to anticipate the acidity changes in ionic media. As the latter is now very popular for replacing volatile organic solvents, it becomes highly desirable to know how the driving force of bond cleavage is varied as the medium composition is switched from neutral molecules to the charged ions. Here we describe a general approach to measure absolute pK(a)'s in pure ionic liquid (IL). The standard conditions warranting accurate measurement were outlined. The pK(a)'s of the selected 18 C-H type indicator acids in four ILs were determined and a convenient indicator platform was constructed for easy expansion of acidity scales. These absolute pK(a)'s make possible, for the first time, direct comparisons of bond energies in IL with those in molecular solvent and in the gas phase and should be able to serve as the standard parameters for calibrating computational methods suitable for the studies in ionic media. The effect of cation and anion in IL in relation to structure was analyzed.

This paper describes a simple chiral primary amine-catalyzed highly efficient and practical protocol for the synthesis of both Wieland-Miescher ketone and Hajos-Parrish ketone as well as their analogues. The reaction can be conducted in gram scale with 1% mol catalyst loading producing high enantioselectivity (up to 96% ee) and excellent yields (up to 98%). This procedure represents one of the most efficient methods for the synthesis of these versatile chiral building blocks.

A highly diastereo- and enantioselective asymmetric allylic alkylation reaction with respect to prochiral 3-substituted benzofuran-2(3H)-ones and MBH carbonate by a chiral biscinchona alkaloid catalyst was investigated. The corresponding adducts, containing a quaternary center at the C3-position of the benzofuran-2(3H)-one as well as a vicinal tertiary center, were generally obtained in high yields (up to 97%) with very good diastereo- (up to 98:2 dr) and enantioselectivities (up to 95% ee).

Although the competitive mechanism for Meisenheimer complex formation during the reaction of 2,4,6-trinitroanisole with methoxide ion in methanol is generally accepted, no kinetic evidence has been presented to rule out a reversible consecutive mechanism. Simulation of the competitive mechanism revealed that a fractional order in [MeO(-)] is predicted by the latter. Conventional pseudo-first-order analysis of the kinetics resulted in cleanly first-order in [MeO(-)], which rules out the competitive mechanism. The kinetic data are consistent with the reversible consecutive mechanism, which is proposed for this important reaction. An intermediate is required for this mechanism, and we propose that a dianion complex (III) is formed reversibly from the initial 1,3-σ complex (I). The trimethoxy complex (III), the (1)H NMR spectrum of which was observed earlier by Servis (Servis, K. L. J. Am. Chem. Soc. 1965, 87, 5495; 1967, 89, 1508), then eliminates methoxide ion reversibly to form the 1,1-σ complex product (II).

A highly diastereo- and enantioselective Michael addition reaction with respect to prochiral 3-substituted benzofuran-2(3H)-ones and maleimides by a chiral bifunctional thiourea-tertiary amine catalyst was investigated. The corresponding adducts, containing a quaternary center at the C3-position of the benzofuran-2(3H)-one as well as a vicinal tertiary center, were generally obtained in high yields (up to 99%) with very good diastereo- (up to >20:1 dr) and enantioselectivities (up to 97% ee).

Highly syn-selective cross-aldol reaction of aldehydes has remained a challenging subject in the field of aminocatalysis. To achieve this end, chiral primary amines have been explored and the primary-tertiary diamine-Brønsted acid salts are found to promote the cross-aldol reactions of aldehydes with high activity and syn selectivity. Among various vicinal diamines screened, l-phenylalanine derived 2a/TfOH conjugate is identified as the optimal catalyst, showing good catalytic activity (up to 97% yield) and high syn selectivities (syn/anti up to 24:1, 87% ee). The current catalysis works selectively with small aliphatic aldehydes donors such as propionaldehyde and isobutyraldehyde, but not with aliphatic aldehydes bearing larger beta-substitute (>Me). In addition, the use of 2a/TfOH conjugate has also enabled the first syn-selective cross-aldol reactions of glycoaldehyde donors.

An asymmetric direct aldol reaction of acetoacetals is described. Under the catalysis of a simple chiral primary amine, the direct aldol reactions of acetoacetals occur exclusively on the gamma-position to give vinylogous-type aldol products with high diastereo- and enantioselectivity.

The first set of experimentally determined C-NO bond homolytic and heterolytic dissociation enthalpies in solution is derived by using direct titration calorimetry combined with appropriate electrode potentials through thermodynamic cycles. The homolytic bond dissociation energy scale (BDEs) of the corresponding C-NO bonds in the gas phase was also calculated at the MP2/6-311+G**//B3LYP/6-31G* level and BP86/6-31G*//B3LYP/6-31G* level of theory for the purpose of comparison. The C-NO and S-NO bond thermodynamic parameters were used to predict the trend of NO transfer from C-nitroso substrates to thiols in acetonitrile solution.

The hydride affinities (defined as the enthalpy changes in this work) of 15 polarized dienes [five phenyl sulfone substituted allenes (1a), the corresponding five isolated dienes (1b), and the corresponding five conjugated dienes (1c)] in acetonitrile solution were determined by titration calorimetry for the first time. The results display that the hydride affinity scales of the 15 dienes in acetonitrile range from -71.6 to -73.9 kcal/mol for 1a, from -46.2 to -49.7 kcal/mol for 1b, and from -45.0 to -46.5 kcal/mol for 1c, which indicates that the hydride-obtaining abilities of the cumulated dienes (1a) are not only much larger than those of the corresponding conjugated dienes (1c) but also much larger than those of the corresponding isolated dienes (1b). The hydrogen affinities of the 15 dienes as well as the hydrogen affinities and the proton affinities of the radical anions of the dienes (1(-*)) in acetonitrile were also evaluated by using relative thermodynamic cycles according to Hess's law. The results show that (i) the hydrogen affinities of the neutral dienes 1 cover a range from -44.5 to -45.6 kcal/mol for 1a, from -20.4 to -21.4 kcal/mol for 1b, and from -17.3 to -18.5 kcal/mol for 1c; (ii) the hydrogen affinities of the radical anions of the dienes (1(-*)) in acetonitrile cover a range from -40.6 to -47.2 kcal/mol for 1a(-*), from -21.6 to -29.6 kcal/mol for 1b(-*), and from -10.0 to -15.4 kcal/mol for 1c(-*); (iii) the proton affinities of the 15 1a(-*) in acetonitrile cover a range from -97.0 to -100.6 kcal/mol for 1a(-*), from -77.8 to -83.4 kcal/mol for 1b(-*), and from -66.2 to -68.9 kcal/mol for 1c(-*). The main reasons for the great difference between the cumulated dienes and the corresponding isolated and conjugated dienes in the hydride affinity, hydrogen affinity, and proton affinity have been examined. It is evident that these experimental results should be quite valuable to facilitate the elucidation of the origins of the especially high chemical potencies of the allenes, the choice of suitable hydride reducing agents to reduce the dienes, and the analyses on the reduction mechanisms.

The first heterolytic and homolytic N(O)-NO(2) bond dissociation energy scales of three types Y-nitro (Y = N, O) compounds and corresponding radical anions in acetonitrile were established by using titration calorimetry combined with relevant electrochemical data through proper thermodynamic cycles.

Functionalized chiral ionic liquids were found to be highly effective and reusable organocatalysts for asymmetric Michael additions of 4-substituted cyclohexanones. The desymmetrization reaction afforded the desired Michael adducts bearing three carbon stereocenters with up to 99% ee.