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Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine‐mediated radical process for C(sp2)−H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late‐stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway. [ABSTRACT FROM AUTHOR]

Transition metal intermediates bearing M−X σ‐bonds are ubiquitous in metal‐mediated C−X bond transformations. Thermodynamic knowledge of M−X bond cleavage is crucial to explore relevant reactions; but little was accumulated till present due to lack of suitable determination methods. We here report the first systematic study of the Pd−X bond homolysis dissociation free energies [BDFE(Pd−X)] of representative [(tmeda)Pd(4‐F−C6H4)X] (tmeda=N,N,N′,N′‐tetramethylethylenediamine, X=OR or NHAr) in DMSO on the basis of reliable measurement of their bond heterolysis energies (ΔGhet(Pd−X)). Despite ΔGhet(Pd−O)s of palladium‐phenoxides are generally found about 8 kcal/mol smaller than ΔGhet(Pd−N)s of palladium‐amidos, their BDFE(Pd−X)s are observed comparable. The structure‐property relationship was investigated to disclose an enhancement effect of electron‐withdrawing groups on BDFE(Pd−X)s. Linear free energy relationship analysis revealed that Pd−X bonds are more sensitive than X−H bonds to structural variation. The energetic propensity of reductive elimination from arylpalladium complexes was evaluated by combinatorial use of BDFE(Pd−X)s and BDFE(C−X)s, indicating an overall thermodynamic bias to C−N bond formation. [ABSTRACT FROM AUTHOR]

The unique heterocyclic skeletons of N-heterocyclic phosphines (NHPs) endow them with excellent hydridic reactivity, which has enabled NHPs to be applied in a great array of catalytic hydrogenations of unsaturated substrates in the past few decades. Recently, applications of NHPs in radical reductions, especially in a catalytic fashion, have emerged as a promising forefront area. This new reaction pattern, distinctive from but complementary to the well-established hydride pathway, can greatly expand the reaction scope to σ-bond scission. Herein, we briefly summarized some representative examples of synthetic applications of NHPs in both hydridic and radical reductions with an emphasis on their radical reactivity, including the structural and property studies of NHP radicals and their precursors as well as their applications in radical processes. [ABSTRACT FROM AUTHOR]

A Huisgen 1,3-dipolar cycloaddition 'click chemistry' was employed to immobilize azido sugars (mannose, lactose, [alpha]-Gal) to fabricate carbohydrate self-assembled monolayers (SAMs) on gold. This fabrication was based on preformed SAM templates incorporated with alkyne terminal groups, which could further anchor the azido sugars to form well-packed, stable, and rigid sugar SAMs. The clicked mannose, lactose, and [alpha]-Gal trisaccharide SAMs were used in the analysis of specific carbohydrate-protein interactions (i.e., mannose--Con A; ECL--lactose, ([alpha]-Gal--anti-Gal). The apparent affinity constant of Con A binding to mannose was (8.7 [+ or -] 2.8) x [10.sup.5] and (3.9 [+ or -] 0.2) x [10.sup.6] [M.sup.-1] measured by QCM and SPR, respectively. The apparent affinity constants of lactose binding with ECL and (x-Gal binding with polyclonal anti-Gal antibody were determined to be (4.6 [+ or -] 2.4) x [10.sup.6] and (6.7 [+ or -] 3.3) x [10.sup.6] [M.sup.-1], respectively by QCM. SPR, QCM, AFM, and electrochemistry studies confirmed that the carbohydrate SAM sensors maintained the specificity to their corresponding lectins and nonspecific adsorption on the clicked carbohydrate surface was negligible. This study showed that the clicked carbohydrate SAMs in concert with nonlabel QCM or SPR offered a potent platform for high-throughput characterization of carbohydrate-protein interactions. Such a combination should complement other methods such as ITC and ELISA in a favorable manner and provide insightful knowledge for the corresponding complex glycobiological processes.

O-type variations on C-H bond dissociation energies were studied.

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.

Equilibrium acidities in DMSO for phenylhydrazine, five p-substituted derivatives, 1,2-diphenylhydrazine and 1,1,2-triphenylhydrazine were measured. The bond dissociation enthalpies (BDEs) of their acidic N-H bonds were estimated. The alpha-N-H bonds in CHsub3CONHNHsub2, PhCONHNHsub2, NHsub2NHCOsub2Et and PhSOsub2NHNHsub2 hydrazides were more acidic than the alpha-N-H bonds in corresponding amides, and the BDEs were weaker.

The enantioselective aza‐Diels–Alder reaction is efficient for constructing chiral tetrahydropyridines, but the catalytic asymmetric aza‐Diels–Alder reaction of ketimines with unactivated dienes is still a challenging topic. Herein, guided by computational screening, a highly enantioselective aza‐Diels–Alder reaction of 2‐aryl‐3H‐indol‐3‐ones with unactivated dienes was realized by using a B(C6F5)3/chiral phosphoric acid catalyst system under mild conditions. The reaction has a broad scope with respect to both aza‐Diels–Alder reaction partners and hence offers rapid access to an array of tetrahydropyridine derivatives with pretty outcomes (up to 99 % yield, >20:1 dr and 98:2 er). The reaction is very efficient: lowering catalyst loadings for the model reaction to 0.1 mol %, enantioselectivity is still maintained. The synthetic utility was confirmed by transformations of the products. DFT calculations provide convincing evidence for the interpretation of stereoselection. [ABSTRACT FROM AUTHOR]

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.

The delta G(sub hydride) (R+) data for some stable carbocations and less stable aromatic carbocations derived from substituted toluenes, fluorenes and 9-methylanthracenes are reported. The computation of hydride affinities of organic cations was based on two equations derived from thermochemical cycles. Linear correlations were observed between hydride affinities and solution electron affinities of hydride acceptors. Correlations between delta G(sub hydride)(R+) and pK(sub R+) of corresponding carbinols provide convenient estimates of each other as long as the other is known.

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.

A thermodynamic study of the cleavage of carbon-sulfur bonds involves the analysis of the enthalpies of reactions between six thiophenoxides and fiveresonance-stabilized carbenium ions. C-S bond cleavage is of interest in the environmentally-critical desulfurization of coal. A battery of calorimetric andvoltammetric tests yield correlated data on the heats of heterolysis and homolysis, redox potentials and heats of entropies of the various processes involved in the reactions. These are presented and discussed in detail.

Fluorine incorporation into organic molecules is expected to lower the pKa of neighboring functionality via its strong electron‐withdrawing effect, and this strategy has been widely exploited in diverse disciplines. Herein, we report a striking anomalous α‐fluorine substitution effect on the α‐Csp3‐H acidity. We have experimentally measured the pKa values of a series of popular nucleophilic monofluoromethylating reagents α‐fluoro(phenylsulfonyl)methane derivatives as well as their C‐H analogues by Bordwell's overlapping indicator method in dimethyl sulfoxide solution. Contrary to expectations, we found that α‐fluorine substituent does not generally enhance but rather weaken the α‐Csp3‐H acidity of most (phenylsulfonyl)methane derivatives. DFT computations reproduce and provide insight into the anomalous α‐fluorine effect. A correlation was identified between the C‐H pKa of (phenylsulfonyl)methane derivatives and Mayr's nucleophilicity parameter (N) of the corresponding carbanions. [ABSTRACT FROM AUTHOR]

N-heterocyclic phosphines (NHPs) have recently emerged as a new group of promising catalysts for metal-free reductions, owing to their unique hydridic reactivity. The excellent hydricity of NHPs, which rivals or even exceeds those of many metal-based hydrides, is the result of hyperconjugative interactions between the lone-pair electrons on N atoms and the adjacent σ*(P–H) orbital. Compared with the conventional protic reactivity of phosphines, this umpolung P–H reactivity leads to hydridic selectivity in NHP-mediated reductions. This reactivity has therefore found many applications in the catalytic reduction of polar unsaturated bonds and in the hydroboration of pyridines. This review summarizes recent progress in studies of the reactivity and synthetic applications of these phosphorus-based hydrides, with the aim of providing practical information to enable exploitation of their synthetically useful chemistry. [ABSTRACT FROM AUTHOR]

Thermodynamic knowledge of the metal–ligand (M−L) σ‐bond strength is crucial to understanding metal‐mediated transformations. Here, we developed a method for determining the Pd−X (X=OR and NHAr) bond heterolysis energies (ΔGhet(Pd−X)) in DMSO taking [(tmeda)PdArX] (tmeda=N,N,N′,N′‐tetramethylethylenediamine) as the model complexes. The ΔGhet(Pd−X) scales span a range of 2.6–9.0 kcal mol−1 for ΔGhet(Pd−O) values and of 14.5–19.5 kcal mol−1 for ΔGhet(Pd−N) values, respectively, implying a facile heterolytic detachment of the Pd ligands. Structure‐reactivity analyses of a modeling Pd‐mediated X−H bond activation reveal that the M−X bond metathesis is dominated by differences of the X−H and Pd−X bond strengths, the former being more influential. The ΔGhet(Pd−X) and pKa(X−H) parameters enable regulation of reaction thermodynamics and chemoselectivity and diagnosing the probability of aniline activation with Pd−X complexes. [ABSTRACT FROM AUTHOR]

An efficient asymmetric allylation reaction of allylboronates with seven-membered cyclic imines, dibenzo[b,f][1,4]oxazepines, is described. The reaction, which is catalyzed by a Bi(OAc)3/CPA system, gives a range of chiral nitrogen-containing heterocycle structures in high yields and with good enantioselectivities. The conversion of these products to nitrogen-containing heterocycles is also demonstrated. [ABSTRACT FROM AUTHOR]

While many approaches to predict aqueous pKa values exist, the fast and accurate prediction of non‐aqueous pKa values is still challenging. Based on the iBonD experimental pKa database (39 solvents), a holistic pKa prediction model was established using machine learning. Structural and physical‐organic‐parameter‐based descriptors (SPOC) were introduced to represent the electronic and structural features of the molecules. The models trained with a neural network or the XGBoost algorithm showed the best prediction performance with a low MAE value of 0.87 pKa units. The approach allows a comprehensive mapping of all possible pKa correlations between different solvents and it was validated by predicting the aqueous pKa and micro‐pKa of pharmaceutical molecules and pKa values of organocatalysts in DMSO and MeCN with high accuracy. An online prediction platform was constructed based on the current model, which can provide pKa prediction for different types of X−H acidity in the most commonly used solvents. [ABSTRACT FROM AUTHOR]

An efficient asymmetric aza-Friedel–Crafts reaction of phenols with isatin-derived ketimines is described. The reaction, which was promoted by a Bi(OH)3/CPA system, gave a series of chiral 3-amino-2-oxindoles with high yields (up to 99%), excellent enantioselectivities (up to 99%) and moderate to very good regioselectivities (up to 25/1). [ABSTRACT FROM AUTHOR]