Pd-Catalyzed Vinylation of Aryl Halides with Inexpensive Organosilicon Reagents Under Mild Conditions.

Pd-catalyzed Hiyama vinylation reaction of non-activated aryl chlorides and bromides under mild conditions was developed. The use of efficient vinyl donors and electron-rich sterically hindered phosphine ligands was critical for the success of the reaction. The products of this transformation can be used for Am/Cm separation, an important challenge in nuclear fuel reprocessing. The substituent effect on Am/Cm separating selectivity was also achieved, which could contribute to the development of new chromatographic materials for the separation of Am and Cm.

Radical Carbofluorination of Unactivated Alkenes with Fluoride Ions.

The copper-assisted radical carbofluorination of unactivated alkenes with fluoride ions is described. With [Cu(L3)F2]H2O (L3 = 4,4'-di(methoxycarbonyl)-2,2'-bipyridine) as the fluorine source and [Ag(DMPhen)(MeCN)]BF4 (DMPhen = 2,9-dimethyl-1,10-phenanthroline) as the chloride scavenger, the reaction of unactivated alkenes with CCl4 in acetonitrile provided the corresponding carbofluorination products in satisfactory yields. The protocol exhibited a wide functional group compatibility and broad substrate scope and could be extended to the use of a variety of activated alkyl chlorides other than CCl4. A copper-catalyzed fluorotrifluoromethylation of unactivated alkenes was then successfully developed with CsF as the fluorine source and Umemoto's reagent as the trifluoromethylating agent. A mechanism involving the fluorine atom transfer from Cu(II)-F complexes to alkyl radicals is proposed.

Selective Radical Fluorination of Tertiary Alkyl Halides at Room Temperature.

Direct fluorination of tertiary alkyl bromides and iodides with Selectfluor is described. The halogen-exchange fluorination proceeds efficiently in acetonitrile at room temperature under metal-free conditions and exhibits a wide range of functional group compatibility. Furthermore, the reactions are highly selective in that alkyl chlorides and primary and secondary alkyl bromides remain intact. A radical mechanism is proposed for this selective fluorination.

Mechanism of Nickel-Catalyzed Suzuki-Miyaura Coupling of Amides.

The Ni-catalyzed Suzuki-Miyaura coupling of N-tert-butoxycarbonyl (N-Boc)-protected amides provides a versatile strategy for the construction of C-C bonds. In this study, density functional theory (DFT) methods have been used to elucidate the mechanism of this reaction, with particular emphasis on the roles of N-Boc, K3 PO4 and H2 O. Our results corroborated those of previous reports, indicating that the overall catalytic cycle consists of three steps, including oxidative addition, transmetalation, and reductive elimination. Three of the possible transmetalation mechanisms were examined to interpret the effects of K3 PO4 and H2 O. According to the most feasible of these transmetalation mechanisms, K3 PO4 (acting as a Lewis base) would initially interact with the Lewis acid PhBpin to give a K3 PO4 -PhBpin complex, which would readily undergo a hydrogen transfer step with H2 O. The H transfer in the transmetalation step was determined to be the rate-determining step. Notably, the theoretical results showed good agreement with the experimental data.

Mechanistic Study on Gold-Catalyzed Highly Selective Hydroamination of Alkylidenecyclopropanes.

Density functional theory calculations have been carried out to study the mechanism of the gold-catalyzed highly selective hydroamination of alkylidenecyclopropanes. Two main mechanisms (i.e., double-bond activation-first and three-membered-ring activation-first mechanisms) have been examined. The double-bond activation-first mechanism results in the alkene hydroamination product, and it mainly consists of three steps: C-N bond formation, C-C bond rotation, and protodeauration (rate-determining step). Meanwhile, the three-membered-ring activation-first mechanism finally produces allylic amines, and it occurs via the ring-opening (rate-determining step), C-N bond formation, and protodeauration steps. The calculation results show good agreement with the experimental outcomes on the chemo-, regio-, and diastereoselectivity. On this basis, we found that the regioselectivity is caused by the C-C bond rotation step, while the diastereoselectivity is determined by both the C-C bond rotation and the protodeauration steps in the double-bond activation-first mechanism.

Mechanism of Ligand-Controlled Regioselectivity-Switchable Copper-Catalyzed Alkylboration of Alkenes.

Cu-catalyzed alkylboration of alkenes with bis(pinacolato)diboron ((Bpin)2 ) and alkyl halides provides a ligand-controlled regioselectivity-switchable method for the construction of complex boron-containing compounds. Here, we employed DFT methods to elucidate the mechanistic details of this reaction and the origin of the different regioselectivity induced by Xantphos and Cy-Xantphos. The calculation results reveal that the catalytic cycle mainly proceeds through the migratory insertion of alkenes on Cu-Bpin complex, the oxidative addition of alkyl halides, and the reductive elimination of a C-C bond. Meanwhile, the rate- determining step is the oxidative addition of alkyl halides and the regioselectivity-determining step is the migratory insertion of alkenes. The bulky cyclohexyl group of Cy-Xantphos facilitates the approach of the substituents of alkenes to Bpin in the migratory insertion step and thus leads to the Markovnikov products. The less bulky phenyl group on Xantphos prefers keeping the substituents of alkenes away from the Bpin moiety in the migratory insertion step and thus results in anti-Markovnikov products.

Mechanism of Boron-Catalyzed N-Alkylation of Amines with Carboxylic Acids.

Mechanistic study has been carried out on the B(C6F5)3-catalyzed amine alkylation with carboxylic acid. The reaction includes acid-amine condensation and amide reduction steps. In condensation step, the catalyst-free mechanism is found to be more favorable than the B(C6F5)3-catalyzed mechanism, because the automatic formation of the stable B(C6F5)3-amine complex deactivates the catalyst in the latter case. Meanwhile, the catalyst-free condensation is constituted by nucleophilic attack and the indirect H2O-elimination (with acid acting as proton shuttle) steps. After that, the amide reduction undergoes a Lewis acid (B(C6F5)3)-catalyzed mechanism rather than a Brønsted acid (B(C6F5)3-coordinated HCOOH)-catalyzed one. The B(C6F5)3)-catalyzed reduction includes twice silyl-hydride transfer steps, while the first silyl transfer is the rate-determining step of the overall alkylation catalytic cycle. The above condensation-reduction mechanism is supported by control experiments (on both temperature and substrates). Meanwhile, the predicted chemoselectivity is consistent with the predominant formation of the alkylation product (over disilyl acetal product).

Density functional theory investigation on Pd-catalyzed cross-coupling of azoles with aryl thioethers.

In the present study, a density functional theory (DFT) study has been carried out on the Pd-catalyzed coupling of azoles with aryl thioethers. Our effort is mainly put into identifying the most feasible catalytic cycle, and especially the origin of chemoselectivity for the exclusive aromatic Csp(2)-S bond activation (in the presence of an alkyl Csp(3)-S bond). The coupling mainly consists of three steps: C-S activation, NaO(t)Bu mediated C-H palladation, and reductive elimination. The Csp(2)-S activation is favored over Csp(3)-S activation, and thus di(hetero)aryls are the predicted products. This conclusion well reproduces Wang's recent experimental observations. The rate- and chemoselectivity determining steps of the C-H/Csp(2)-S activation mechanism are C-H palladation and C-S activation steps, respectively. Analyzing the origin of chemoselectivity, we found that the easiness of Pd catalyzed C-S activation is independent of the C-S bond strengths in thioether substrates. By contrast, d-π* backdonation in Csp(2)-S-Pd intermediates is the main driving force for the favorable Csp(2)-S activation (over the Csp(3)-S activation).

Computational Study of Formic Acid Dehydrogenation Catalyzed by Al(III)-Bis(imino)pyridine.

The mechanism of formic acid dehydrogenation catalyzed by the bis(imino)pyridine-ligated aluminum hydride complex (PDI(2-))Al(THF)H (PDI=bis(imino)pyridine) was studied by density functional theory calculations. The overall transformation is composed of two stages: catalyst activation and the catalytic cycle. The catalyst activation begins with O-H bond cleavage of HCOOH promoted by aluminum-ligand cooperation, followed by HCOOH-assisted Al-H bond cleavage, and protonation of the imine carbon atom of the bis(imino)pyridine ligand. The resultant doubly protonated complex ((H,H) PDI)Al(OOCH)3 is the active catalyst for formic acid dehydrogenation. Given this, the catalytic cycle includes ß-hydride elimination of ((H,H) PDI)Al(OOCH)3 to produce CO2, and the formed ((H,H) PDI)Al(OOCH)2 H mediates HCOOH to release H2.

Ligand-Controlled Regiodivergent Copper-Catalyzed Alkylboration of Alkenes.

A novel copper-catalyzed regiodivergent alkylboration of alkenes with bis(pinacolato)diboron and alkyl halides has been developed. The regioselectivity of the alkylboration was controlled by subtle differences in the ligand structure. The reaction thus enables the practical, regiodivergent synthesis of two different alkyl boronic esters with complex structures from a single alkene.

Mechanism of Nickel(II)-Catalyzed Oxidative C(sp²)-H/C(sp³)-H Coupling of Benzamides and Toluene Derivatives.

The Ni-catalyzed C(sp(2))-H/C(sp(3))-H coupling of benzamides with toluene derivatives was recently successfully achieved with mild oxidant iC3F7I. Herein, we employ density functional theory (DFT) methods to resolve the mechanistic controversies. Two previously proposed mechanisms are excluded, and our proposed mechanism involving iodine-atom transfer (IAT) between iC3F7I and the Ni(II) intermediate was found to be more feasible. With this mechanism, the presence of a carbon radical is consistent with the experimental observation that (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) completely quenches the reaction. Meanwhile, the hydrogen-atom abstraction of toluene is irreversible and the activation of the C(sp(2))-H bond of benzamides is reversible. Both of these conclusions are in good agreement with Chatani's deuterium-labeling experiments.

Room-Temperature Decarboxylative Couplings of α-Oxocarboxylates with Aryl Halides by Merging Photoredox with Palladium Catalysis.

Enabled by merging iridium photoredox catalysis and palladium catalysis, α-oxocarboxylate salts can be decarboxylatively coupled with aryl halides to generate aromatic ketones and amides at room temperature. DFT calculations suggest that this reaction proceeds through a Pd(0) -Pd(II) -Pd(III) pathway, in which the Pd(III) intermediate is responsible for reoxidizing Ir(II) to complete the Ir(III) -*Ir(III) -Ir(II) photoredox cycle.

Corrigendum.

[This corrects the article on p. 253 in vol. 5, PMID: 25425503.][This corrects the article on p. 171 in vol. 5, PMID: 25192875.][This corrects the article on p. 315 in vol. 5, PMID: 25167857.][This corrects the article on p. 45 in vol. 6.].

Fluorescent recognition of uranyl ions by a phosphorylated cyclic peptide.

Fluorescent recognition of uranyl ions was achieved using a phosphorylated cyclic peptide, which can be used as a fluorescent sensor for the detection of uranyl ions with high selectivity and sensitivity.

"One-pot" synthesis of amidoxime via Pd-catalyzed cyanation and amidoximation.

A novel "one-pot" reaction was developed for the synthesis of aryl or heteroaryl-substituted amidoxime compounds containing various functional groups. Fluorescence titration experiments coupled with theoretical analysis revealed that the steric hindrance and electronic effects of substituents influence the binding ability of the amidoxime compounds to uranyl ions.

Mechanistic origin of chemoselectivity in thiolate-catalyzed Tishchenko reactions.

The thiolate-catalyzed Tishchenko reaction has shown high chemoselectivity for the formation of double aromatic-substituted esters. In the present study, the detailed reaction mechanism and, in particular, the origin of the observed high chemoselectivity, have been studied with DFT calculations. The catalytic cycle mainly consisted of three steps: 1,2-addition, hydride transfer, and acyl transfer steps. The calculation results reproduce the experimental observations that 4-chlorobenzaldehyde acts as the hydrogen donor (carbonyl part in the ester product), while 2-methoxybenzaldehyde acts as the hydrogen acceptor (alcohol part in the product). The two main factors are responsible for such chemoselectivity: 1) in the rate-determining hydride transfer step, the para-chloride substituent facilitates the hydride-donating process by weakening the steric hindrance, and 2) the ortho-methoxy substituent facilitates the hydride-accepting process by stabilizing the magnesium center (by compensating for the electron deficiency).

Accurate predictions of C-SO2R bond dissociation enthalpies using density functional theory methods.

The dissociation of the C-SO2R bond is frequently involved in organic and bio-organic reactions, and the C-SO2R bond dissociation enthalpies (BDEs) are potentially important for understanding the related mechanisms. The primary goal of the present study is to provide a reliable calculation method to predict the different C-SO2R bond dissociation enthalpies (BDEs). Comparing the accuracies of 13 different density functional theory (DFT) methods (such as B3LYP, TPSS, and M05 etc.), and different basis sets (such as 6-31G(d) and 6-311++G(2df,2p)), we found that M06-2X/6-31G(d) gives the best performance in reproducing the various C-S BDEs (and especially the C-SO2R BDEs). As an example for understanding the mechanisms with the aid of C-SO2R BDEs, some primary mechanistic studies were carried out on the chemoselective coupling (in the presence of a Cu-catalyst) or desulfinative coupling reactions (in the presence of a Pd-catalyst) between sulfinic acid salts and boryl/sulfinic acid salts.

Quantum-chemical predictions of pKa's of thiols in DMSO.

The deprotonation of thiols (on the S-H bond) is widely involved in organic and bio-organic reactions. With the aid of density functional theory (DFT) calculations, the present study focuses on predicting the pKa's of thiols. Efforts were first put in searching for an appropriate computational method. To achieve this goal, the accuracy of 13 different DFT functionals (i.e., B3LYP, BB1K, PBE, M06, M05, M06-2X, M06-L, M05-2X, TPSS, MPW1K, MPWB1K, MPW3LYP, TPSSLYP1W) and 6 different total electron basis sets (6-31G(d), 6-31+G(d), 6-31+G(d,p), 6-311+G(d,p), 6-311++G(d,p), 6-311++G(2df,2p)) (with DMSO solvent and SMD solvation model) were examined. The M06-2X/6-311++G(2df,2p) (M1) method was found to give the best performance in reproducing the reported 16 pKa's of thiols, with a standard deviation (SD) of about 0.5 pKa unit. Meanwhile, the M1 method was found to be excellent in reproducing the gas phase Gibbs free energies of 17 thiols, providing extra evidence for the reliability of the M1 method in treating thiol systems. On this basis, M1 was then used to predict the pKa's of 291 thiols whose experimental pKa values remain unknown. Accordingly, the scope of pKa's of different thiols was constructed.

Computational study on mechanism of Rh(III)-catalyzed oxidative Heck coupling of phenol carbamates with alkenes.

A systematic theoretical study on the Rh-catalyzed oxidative Heck-coupling of phenol carbamates with alkenes is carried out. Two possible mechanisms (i.e. arene activation-first and alkene activation-first mechanisms) are examined. As to the C-H activation step, four mechanisms including oxidative addition, electrophilic substitution, concerted metallation-deprotonation (CMD), and σ-bond metathesis are evaluated. The calculation results indicate that the arene activation-first mechanism is more favorable for the overall catalytic cycle. This mechanism involves three steps: arene C-H activation at the position ortho to the carbamate directing group affording a six-membered rhodiacycle intermediate, insertion of the alkene double bond into the Rh(III)-aryl bond, and a final ß-H elimination step to release the product and re-generate the catalyst. The rate determining step of the overall catalytic cycle is the arene C-H activation step, which is found to proceed through the acetate-assisted CMD mechanism.

Mechanism of arylboronic acid-catalyzed amidation reaction between carboxylic acids and amines.

Arylboronic acids were found to be efficient catalysts for the amidation reactions between carboxylic acids and amines. Theoretical calculations have been carried out to investigate the mechanism of this catalytic process. It is found that the formation of the acyloxyboronic acid intermediates from the carboxylic acid and the arylboronic acid is kinetically facile but thermodynamically unfavorable. Removal of water (as experimentally accomplished by using molecular sieves) is therefore essential for overall transformation. Subsequently C-N bond formation between the acyloxyboronic acid intermediates and the amine occurs readily to generate the desired amide product. The cleavage of the C-O bond of the tetracoordinate acyl boronate intermediates is the rate-determining step in this process. Our analysis indicates that the mono(acyloxy)boronic acid is the key intermediate. The high catalytic activity of ortho-iodophenylboronic acid is attributed to the steric effect as well as the orbital interaction between the iodine atom and the boron atom.