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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]

Electrostatic interaction, especially electrostatic attraction, usually plays critical roles in controlling the reactivity and selectivity in catalytic transformations; however, the like-charge repulsion, which is ubiquitous in physical systems, is rarely applied in reaction control. Herein we disclosed an unexpected like-charge repulsion induced enantio-control mode in primary aminecatalyzed fluorination reactions with 1-fluoro-2,4,6-trimethylpyridinium triflate. The ionic reaction works favorably in both highly polar (methanol) and non-polar (hexane) solvents, a seldom observed phenomenon in asymmetric catalysis. Erying plot analysis showed that an inversion temperature existed in MeOH, which was explained by the solvent-solute cluster model under different temperatures. Density functional theory (DFT) study and energy decomposition analysis (EDA) verified that the like-charge repulsion takes effect in polar solvent methanol, while in nonpolar solvents, the steric repulsion associated with ion-pair was found to be the major effect for the observed enantioselectivity. [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]

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]

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]

Fluorine-containing moieties show significant effects in improving the properties of functional molecules. Consequently, efficient methods for installing them into target compounds are in great demand, especially those enabled by metal-free catalysis. Here we show a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry. This metal-free hydrodefluorination features mild reaction conditions, good group compatibility, and almost quantitative yields for both product types. Stoichiometric experiments indicated a stepwise mechanism: hydridic addition to fluoroalkenes and subsequent β-F elimination from hydrophosphination intermediates. Density functional theory calculations disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom. Fluorine-containing moieties show significant effects in improving the properties of functional molecules. Here the authors show diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The enantioselective ketimine–ene reaction is one of the most challenging stereocontrolled reaction types in organic synthesis. In this work, catalytic enantioselective ketimine–ene reactions of 2‐aryl‐3H‐indol‐3‐ones with α‐methylstyrenes were achieved by utilizing a B(C6F5)3/chiral phosphoric acid (CPA) catalyst. These ketimine–ene reactions proceed well with low catalyst loading (B(C6F5)3/CPA=2 mol %/2 mol %) under mild conditions, providing rapid and facile access to a series of functionalized 2‐allyl‐indolin‐3‐ones with very good reactivity (up to 99 % yield) and excellent enantioselectivity (up to 99 % ee). Theoretical calculations reveal that enhancement of the acidity of the chiral phosphoric acid by B(C6F5)3 significantly reduces the activation free energy barrier. Furthermore, collective favorable hydrogen‐bonding interactions, especially the enhanced N−H⋅⋅⋅O hydrogen‐bonding interaction, differentiates the free energy of the transition states of CPA and B(C6F5)3/CPA, thereby inducing the improvement of stereoselectivity. [ABSTRACT FROM AUTHOR]

The enantioselective ketimine–ene reaction is one of the most challenging stereocontrolled reaction types in organic synthesis. In this work, catalytic enantioselective ketimine–ene reactions of 2‐aryl‐3H‐indol‐3‐ones with α‐methylstyrenes were achieved by utilizing a B(C6F5)3/chiral phosphoric acid (CPA) catalyst. These ketimine–ene reactions proceed well with low catalyst loading (B(C6F5)3/CPA=2 mol %/2 mol %) under mild conditions, providing rapid and facile access to a series of functionalized 2‐allyl‐indolin‐3‐ones with very good reactivity (up to 99 % yield) and excellent enantioselectivity (up to 99 % ee). Theoretical calculations reveal that enhancement of the acidity of the chiral phosphoric acid by B(C6F5)3 significantly reduces the activation free energy barrier. Furthermore, collective favorable hydrogen‐bonding interactions, especially the enhanced N−H⋅⋅⋅O hydrogen‐bonding interaction, differentiates the free energy of the transition states of CPA and B(C6F5)3/CPA, thereby inducing the improvement of stereoselectivity. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: Electrophilic trifluoromethylthiolation has emerged as an important and efficient methodology for installing the SCF3 moiety onto an array of organic molecules. Due to the low reactivities of trifluoromethylthiolating reagents, these transformations often require activation through an exogenous Lewis/Brønsted acid. We report herein the quantification of the activation capabilities of Lewis/Brønsted acids for trifluoromethylthiolating reagents through computing the difference in trifluoromethylthio cation donor ability (Tt+DA) between the "activated" and "unactivated" reagent. A moderate correlation is found to exist between the activation capability and Lewis acidity. [ABSTRACT FROM AUTHOR]

The discovery of modern medicine relies on the sustainable development of synthetic methodologies to meet the needs associated with drug molecular design. Heterocycles containing difluoromethyl groups are an emerging but scarcely investigated class of organofluoro molecules with potential applications in pharmaceutical, agricultural and material science. Herein, we developed an organophotocatalytic direct difluoromethylation of heterocycles using O2 as a green oxidant. The C–H oxidative difluoromethylation obviates the need for pre-functionalization of the substrates, metals and additives. The operationally straightforward method enriches the efficient synthesis of many difluoromethylated heterocycles in moderate to excellent yields. The direct difluoromethylation of pharmaceutical moleculars demonstrates the practicability of this methodology to late-stage drug development. Moreover, 2′-deoxy-5-difluoromethyluridine (F2TDR) exhibits promising activity against some cancer cell lines, indicating that the difluoromethylation methodology might provide assistance for drug discovery. Heterocycles containing difluoromethyl groups are molecules with potential application in pharmaceutical, agricultural and materials science. Here, the authors show an organophotocatalytic difluoromethylation of heterocycles using O2 as green oxidant and preliminarily study the products' bioactivity. [ABSTRACT FROM AUTHOR]

Herein, we disclosed an efficient protocol for the construction of chiral 3-allyl-3-hydroxyoxindoles via the enantioselective allylation reaction of isatins and allylboronates catalyzed by a simple binary acid Bi(OAc)3/CPA system under mild conditions. The synthetic utility of this strategy has been demonstrated through the formal synthesis of ent-CPC-1. [ABSTRACT FROM AUTHOR]

This account summarizes our recent work on the p K a scales of some frequently used organocatalysts, especially those of hydrogen-bond-donor catalysts and stronger Brønsted acid catalysts. Most of these p K a values were obtained by the Bordwell overlapping indicator method, which is known to provide high accuracy. Linear free-energy relationships associated with p K a values are discussed in relation to understanding of reaction mechanisms. 1 Introduction 2 Single Hydrogen-Bonding Donors 2.1 Proline-Type Organocatalysts 2.2 Cinchona Alkaloids Bearing a Hydrogen-Bonding Donor in the 6′-Position 3 Double-Hydrogen-Bonding Donors 3.1 Thioureas 3.2 Squaramides 3.3 BINOLs 4 Stronger Brønsted Acids 5 N-Heterocyclic Carbenes 6 Summary and Outlook [ABSTRACT FROM AUTHOR]

The past decade has witnessed a booming growth of research activity in catalytic imine reduction, due to the ongoing motivation to find more efficient conversions of the rather unreactive C=N bonds to the desired C–N segments found in many pharmaceuticals. While several timely reviews have well documented various C=N reduction methodologies with respect to the type of catalyst (acid, base, or transition metal), a detailed discussion of the core role of thermodynamic driving forces in governing these catalyses is still lacking, however. Hence, this tutorial review describes some of the most practical considerations for adjusting reduction thermodynamics by choosing appropriate catalytic strategies, in order to make the target reduction energetically feasible. The combined use of relevant thermodynamic parameters of the substrate imines, hydrogen donors, and catalysts in realizing such a goal is demonstrated on the basis of the energetics of the possible elementary paths. Experimental observations from the literature that are in line with the present energetics-based analyses are exemplified. [ABSTRACT FROM AUTHOR]

A highly diastereoselective and enantioselective Michael addition/desymmetrization reaction of maleimides with prochiral 3- substituted phthalides catalyzed by quinine-derived bifunctional thiourea was realized. A broad range of the 3,3′-disubstituted phthalides bearing vicinal quaternary-tertiary stereogenic centers were synthesized in moderate to good yields (up to 96%) with high diastereoselectivities (up to >19:1 dr) and enantioselectivities (up to 96:4 er). [ABSTRACT FROM AUTHOR]

Nucleophilicity parameters (N, sN) of a group of representative diazaphospholenium hydrides were derived by kinetic investigations of their hydride transfer to a series of reference electrophiles with known electrophilicity (E) values, using the Mayr equation log k2=sN(N+E). The N scale covers over ten N units, ranging from the most reactive hydride donor (N=25.5) to the least of the scale (N=13.5). This discloses the highest N value ever quantified in terms of Mayr's nucleophilicity scales reported for neutral transition‐metal‐free hydride donors and implies an exceptional reactivity of this reagent. Even the least reactive hydride donor of this series is still a better hydride donor than those of many other nucleophiles such as the C−H, B−H, Si−H and transition‐metal M−H hydride donors. Structure–reactivity analysis reveals that the outstanding hydricity of 2‐H‐1,3,2‐diazaphospholene benefits from the unsaturated skeleton. P−H superhydrides: The unexpected philicity of P−H bonds in diazaphospholenes has made their applications to catalytic reductions a burgeoning field. A three‐parameter kinetic equation was used to evaluate their nucleophilicity parameters (N), which cover over ten N units. Kinetic studies imply their much superior hydricity over commonly used hydrides, with 2‐H‐1,3,2‐diazaphospholene being the strongest nucleophilic donor ever quantified by the Mayr equation. [ABSTRACT FROM AUTHOR]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: The electrophilicity parameters (E) of some trifluoromethylthiolating and difluoromethylthiolating reagents were determined by following the kinetics of their reactions with a series of enamines and carbanions with known nucleophilicity parameters (N, sN), using the linear free‐energy relationship log k2=sN(N+E). The electrophilic reactivities of these reagents cover a range of 17 orders of magnitude, with Shen and Lu's reagent 1 a being the most reactive and Billard's reagent 1 h being the least reactive electrophile. While the observed electrophilic reactivities (E) of the amido‐derived trifluoromethylthiolating reagents correlate well with the calculated Gibbs energies for heterolytic cleavage of the X−SCF3 bonds (Tt+DA), the cumol‐derived reagents 1 f and 1 g are more reactive than expected from the thermodynamics of the O−S cleavage. The E parameters of the tri/difluoromethylthiolating reagents derived in this work provide an ordering principle for their use in synthesis. [ABSTRACT FROM AUTHOR]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Free energy relationship (FER) studies to correlate steric parameters with the enantiocatalytic performance of bifunctional tertiary-amine hydrogen-bonding catalysts, including ( S, S)-cyclohexane-1,2-diamine-derived thioureas, Cinchona alkaloid derived thioureas, and ( S, S)-cyclohexane-1,2-diamine-derived squaramides, in Michael reactions revealed that the reactions are much favored by catalysts with less bulky N-substituents. The observed FERs are independent of the chiral scaffold and hydrogen-bond donor, and deepen the understanding of current bifunctional hydrogen-bonding catalysts. Moreover, DFT calculations were performed to interpret the observed high reactivities of thioureas with less bulky substituents. In particular, the computations demonstrated the advantage of a benzyl thiourea catalyst, in which an extra CH ⋅⋅⋅π interaction between catalyst and substrate is the key factor. [ABSTRACT FROM AUTHOR]

Identifying the ability of traditional electrophilic trifluoromethylating reagents as CF3· radical sources offers a great opportunity for developing new radical trifluoromethylation reactions. Herein, we report the first extensive assessment of the propensity of these reagents to donate a CF3· radical by computing X−CF3 bond homolytic dissociation enthalpies. Single electron reduction has a substantial effect on activating the X−CF3 bond, thereby significantly facilitating a CF3 radical release. The quantitative information provided here could be valuable for mechanistic understanding and the rational design of new radical trifluoromethylation reactions. [ABSTRACT FROM AUTHOR]

A highly predictive model to correlate the steric and electronic parameters of tertiary amine thiourea catalysts with the stereoselectivity of Michael reactions of 3-substituted benzofuranones and alkyl 2-phthalimidoacrylates is described. As predicted, new 3,5-bis(trifluoromethyl)benzyl- and methyl-substituted tertiary amine thioureas turned out to be highly suitable catalysts for this reaction and enabled the synthesis of enantioenriched α-amino acid derivatives with 1,3-nonadjacent stereogenic centers. [ABSTRACT FROM AUTHOR]

A highly predictive model to correlate the steric and electronic parameters of tertiary amine thiourea catalysts with the stereoselectivity of Michael reactions of 3-substituted benzofuranones and alkyl 2-phthalimidoacrylates is described. As predicted, new 3,5-bis(trifluoromethyl)benzyl- and methyl-substituted tertiary amine thioureas turned out to be highly suitable catalysts for this reaction and enabled the synthesis of enantioenriched α-amino acid derivatives with 1,3-nonadjacent stereogenic centers. [ABSTRACT FROM AUTHOR]

An asymmetric 1,6-conjugate addition of thioacetic acid with para-quinone methides has been developed by using chiral phosphoric acid catalysis in the presence of water. A series of sulfur-containing compounds were thus obtained in high yields with good to excellent enantioselectivities. Theoretical studies indicated that the water-bridged proton transfer is a potentially favorable reaction pathway. An unprecedented O−H⋅⋅⋅π interaction between water and the aromatic nucleus of chiral phosphoric acid was discovered to contribute significantly to the stereocontrol in the catalysis. [ABSTRACT FROM AUTHOR]

An asymmetric 1,6-conjugate addition of thioacetic acid with para-quinone methides has been developed by using chiral phosphoric acid catalysis in the presence of water. A series of sulfur-containing compounds were thus obtained in high yields with good to excellent enantioselectivities. Theoretical studies indicated that the water-bridged proton transfer is a potentially favorable reaction pathway. An unprecedented O−H⋅⋅⋅π interaction between water and the aromatic nucleus of chiral phosphoric acid was discovered to contribute significantly to the stereocontrol in the catalysis. [ABSTRACT FROM AUTHOR]

A visible-light-mediated, organic photocatalytic stereoselective radical cascade cyclization of polyprenoids is described. The desired cascade cyclization products are achieved in good yields and high stereoselectivities with eosin Y as photocatalyst in hexafluoro-2-propanol. The catalyst system is also suitable for 1,3-dicarbonyl compounds, which require only catalytic amounts of LiBr to promote the formation of the corresponding enols. [ABSTRACT FROM AUTHOR]

An efficient asymmetric allylic alkylation reaction with respect to 3-alkylidene oxindoles and racemic Morita–Baylis–Hillman carbonate has been achieved by using a chiral biscinchona alkaloid catalyst, which delivers the γ-substituted alkylideneoxindoles with a chiral tertiary center in moderate to good yields (up to 92%) and very good enantioselectivities (up to ＞99% ee). [ABSTRACT FROM AUTHOR]

A highly enantioselective b-isocupreidine (b-ICD) catalyzed synthesis of dihydropyran-fused benzofurans through [4+2] cycloaddition of allenoates and benzofuranone alkenes was developed. Switchable chirality inversion of cycloaddition products was achieved by replacing the phenolic proton of the catalyst with a methyl, demonstrating an amazing effect of minimal structural variation on inverting enantioselectivity. DFT calculations were utilized to elucidate the origin of the observed phenomena. Computation also provided a clue for a rational design in which the multi-hydrogen bond with the alcohol additive was found to improve the enantioselectivity of the cycloaddition. Finally, the substrate scope was examined, in which a number of functionalized dihydropyran-fused benzofurans could be obtained in high yields (up to 97%) with very good regio- (>20:1) and enantioselectivities (up to 98:2 e.r.). [ABSTRACT FROM AUTHOR]

Electrocatalytic water oxidation using the oxidatively robust 2,7-[bis(2-pyridylmethyl)aminomethyl]-1,8-naphthyridine ligand (BPMAN)-based dinuclear copper(II) complex, [Cu2(BPMAN)(μ-OH)]3+, has been investigated. This catalyst exhibits high reactivity and stability towards water oxidation in neutral aqueous solutions. DFT calculations suggest that the OO bond formation takes place by an intramolecular direct coupling mechanism rather than by a nucleophilic attack of water on the high-oxidation-state CuIVO moiety. [ABSTRACT FROM AUTHOR]

Electrocatalytic water oxidation using the oxidatively robust 2,7-[bis(2-pyridylmethyl)aminomethyl]-1,8-naphthyridine ligand (BPMAN)-based dinuclear copper(II) complex, [Cu2(BPMAN)(μ-OH)]3+, has been investigated. This catalyst exhibits high reactivity and stability towards water oxidation in neutral aqueous solutions. DFT calculations suggest that the OO bond formation takes place by an intramolecular direct coupling mechanism rather than by a nucleophilic attack of water on the high-oxidation-state CuIVO moiety. [ABSTRACT FROM AUTHOR]