Cover Picture: Theoretical Study on the Halogen–Zinc Exchange Reaction by Using Organozincate Compounds (Chem. Eur. J. 23/2009)

Density functional theory and fragment‐energy analysis have been used to probe the mechanism of the halogen–zinc exchange reaction. In their Full Paper on page 5686 ff. , M. Uchiyama, S. Nakamura et al. discuss three important factors in this reaction: The effect of the halogen species, the effect of the alkyl ligand on zinc, and the effect of the substrate nature.

     

Homoleptic Zincate‐Promoted Room‐Temperature Halogen–Metal Exchange of Bromopyridines

Homoleptic lithium tri‐ and tetraalkyl zincates were reacted with a set of bromopyridines. Efficient and chemoselective bromine–metal exchanges were realized at room temperature with a substoichiometric amount of nBu₄ZnLi₂?TMEDA reagent (1/3 equiv; TMEDA=N,N,N′,N′‐tetramethylethylenediamine). This reactivity contrasted with that of tBu₄ZnLi₂?TMEDA, which was inefficient below one equivalent. DFT calculations allowed us to rationalize the formation of N???Li stabilized polypyridyl zincates in the reaction. The one‐pot difunctionalization of dibromopyridines was also realized using the reagent stoichiometrically. The direct creation of C? Zn bonds in bromopyridines enabled us to perform efficient Negishi‐type cross‐couplings.     

The Halogen–Samarium Exchange Reaction: Synthetic Applications and Kinetics

Fast I/Sm and Br/Sm exchanges take place when various aromatic or heterocyclic iodides and bromides are treated with nBu₂SmCl?4 LiCl and nBu₃Sm?5 LiCl, respectively. The resulting organosamarium reagents were efficiently quenched with aldehydes, ketones, and imines. Also, they undergo acylations when treated with N,N‐dimethylamides leading to ketones. The rate of the Br/Sm exchange for a typical aryl bromide was determined and found to be 8.5×10⁵ faster than the Br/Mg exchange, indicating that the rate of a metal‐exchange is related to the ionic character of the carbon–metal bond and to the metal electronegativity.     

Preparation of Functionalized Diaryl‐ and Diheteroaryllanthanum Reagents by Fast Halogen–Lanthanum Exchange

Aryl and heteroaryl halides (X=Br, I) undergo a fast and convenient halogen–lanthanum exchange with nBu₂LaMe, which leads to functionalized diaryl‐ and diheteroaryllanthanum derivatives. Subsequent trapping reactions with selected electrophiles, such as ketones, aldehydes, or amides, proceeded smoothly at −50 °C in THF, affording polyfunctionalized alcohols and carbonyl derivatives. Kinetic competition experiments revealed a similar reactivity trend as for Br/Mg exchange, but 10⁶‐times higher rates, making it comparable to Br/Li exchange.     

Deprotonative Metalation of Substituted Benzenes and Heteroaromatics Using Amino/Alkyl Mixed Lithium–Zinc Combinations

Different homoleptic and heteroleptic lithium–zinc combinations were prepared, and structural elements obtained on the basis of NMR spectroscopic experiments and DFT calculations. In light of their ability to metalate anisole, pathways were proposed to justify the synergy observed for some mixtures. The best basic mixtures were obtained either by combining ZnCl₂ ? TMEDA (TMEDA=N,N,N′,N′‐tetramethylethylenediamine) with [Li(tmp)] (tmp=2,2,6,6‐tetramethylpiperidino; 3 equiv) or by replacing one of the tmp in the precedent mixture with an alkyl group. The reactivity of the aromatic lithium zincates supposedly formed was next studied, and proved to be substrate‐, base‐, and electrophile‐dependent. The aromatic lithium zincates were finally involved in palladium‐catalyzed cross‐coupling reactions with aromatic chlorides and bromides.     

Zinc Porphyrin Metal‐Center Exchange at the Solid–Liquid Interface

Demetalation of zinc 5,10,15,20‐tetraphenylporphyrin (ZnTPP) under acidic conditions and ion exchange with Cu²⁺ ions at neutral pH are both rapid reactions in the liquid medium. However, for ZnTPP monolayers adsorbed on a Au(111) surface exposed to aqueous solution, we find that, although ion exchange takes place rapidly as expected, demetalation does not occur, even at pH values as low as 0. Based on this, we conclude that metal center exchange on the surface does not proceed through a free‐base porphyrin as an intermediate. Furthermore, once formed, CuTPP is stable on the surface and the reverse exchange from CuTPP to ZnTPP in the presence of Zn²⁺ ions could not be achieved. The preference for copper is so strong that even an attempt to exchange adsorbed ZnTPP with Ni²⁺ ions in the presence of traces of Cu²⁺ yielded CuTPP rather than NiTPP.     

Atom‐Precise Organometallic Zinc Clusters

The bottom‐up synthesis of organometallic zinc clusters is described. The cation {[Zn₁₀](Cp*)₆Me}⁺ ( 1 ) is obtained by reacting [Zn₂Cp*₂] with [FeCp₂][BAr₄^F] in the presence of ZnMe₂. In the presence of suitable ligands, the high reactivity of 1 enables the controlled abstraction of single Zn units, providing access to the lower‐nuclearity clusters {[Zn₉](Cp*)₆} ( 2 ) and {[Zn₈](Cp*)₅(^tBuNC)₃}⁺ ( 3 ). According to DFT calculations, 1 and 2 can be described as closed‐shell species that are electron‐deficient in terms of the Wade–Mingos rules because the apical ZnCp* units that constitute the cluster cage do not have three, but only one, frontier orbitals available for cluster bonding. Zinc behaves flexibly in building the skeletal metal–metal bonds, sometimes providing one major frontier orbital (like Group 11 metals) and sometimes providing three frontier orbitals (like Group 13 elements).     

Mechanism of Ketone Allylation with Allylboronates as Catalyzed by Zinc Compounds: A DFT Study

The mechanism of the allylation reaction between 4‐chloroacetophenone and pinacol allylboronates catalyzed by ZnEt₂ with alcohols was investigated using density functional theory (DFT) at the M05‐2X/6‐311++G(d,p) level. The calculations reveal that the reaction prefers to proceed through a double γ‐addition stepwise reaction mechanism rather than a Lewis acid‐catalyzed concerted one. The intermediate with a four‐coordinated boron center, which is formed through proton transfer from EtOH to the ethyl group of ZnEt₂ mediated by the boron center, is the active species and an entrance for the catalytic cycle. The latter is composed of three elementary steps: 1) boron to zinc transmetalation leading to the formation of allylzincate species, 2) electrophilic addition of ketone to allylzincate species, and 3) generation of the final product with recovery of the catalyst. The boron to zinc transmetalation step has the largest energy barrier of 61.0 kJ mol^?1 and is predicted to be the rate‐determining step. The calculations indicate that the additive EtOH plays important roles both in lowering the activation free energy for the formation of the four‐coordinated boron active intermediate and in transforming the low catalytic activity ZnEt₂ into high activity zinc alkoxide species. The alcohols with a less sterically encumbering R group might be the effective additives. The substituted groups on the allylboronates might primarily affect the boron to zinc transmetalation, and the allylboronates with substituents on the C_γ atom is poor in reactivity. The comparison of the catalytic effect between the zinc compounds investigated suggest that Zn(OEt)₂, Zn(OH)₂, and ZnF₂ exhibit higher catalytic efficiency for the boron to zinc transmetalation due to the activation of the B? C_α bond through orbital interactions between the p orbitals of the EtO, OH, F groups and the empty p orbital of the boron center.     

Density Functional Theory Investigation of the Alkyl–Alkyl Negishi Cross‐Coupling Reaction Catalyzed by N‐Heterocyclic Carbene (NHC)–Pd Complexes

Why bigger is better : A “steric wall” created by the N‐(2,6‐diisopropylphenyl) substituent on the bulky NHC ligand IPr (1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) guides the reactants to and from the Pd center through weak, fleeting (IPr)H–Pd interactions that help the oxidative addition intermediate escape “the anti‐trap”. The alternative “side” approach leads to transmetalation (the rate‐limiting step) for which a novel Pd–Zn interaction was identified.

     

Ligand‐Exchange Processes on Solvated Zinc Cations: Water Exchange on [Zn(H2O)4(L)]2+⋅2 H2O (L=Heterocyclic Ligand)

The water‐exchange mechanisms of [Zn(H₂O)₄(L)]²⁺?2 H₂O (L=imidazole, pyrazole, 1,2,4‐triazole, pyridine, 4‐cyanopyridine, 4‐aminopyridine, 2‐azaphosphole, 2‐azafuran, 2‐azathiophene, and 2‐azaselenophene) have been investigated by DFT calculations (RB3LYP/6‐311+G**). The results support limiting associative reaction pathways that involve the formation of six‐coordinate intermediates [Zn(H₂O)₅(L)]²⁺?H₂O. The basicity of the coordinated heterocyclic ligands shows a good correlation with the activation barriers, structural parameters, and stability of the transition and intermediate states.     

New Mechanistic Insight into Stepwise Metal‐Center Exchange in a Metal–Organic Framework Based on Asymmetric Zn4 Clusters

Herein, a mechanism of stepwise metal‐center exchange for a specific metal–organic framework, namely, [Zn₄(dcpp)₂(DMF)₃(H₂O)₂]_n (H₄dcpp=4,5‐bis(4′‐carboxylphenyl)phthalic acid), is disclosed for the first time. The coordination stabilities between the central metal atoms and the ligands as well as the coordination geometry are considered to be dominant factors in this stepwise exchange mechanism. A new magnetic analytical method and a theoretical model confirmed that the exchange mechanism is reasonable. When the metathesis reaction occurs between Cu^II ions and framework Zn^II ions, the magnetic exchange interaction of each pair of Cu^II centers gradually strengthens with increasing amount of framework Cu^II ions. By analyzing the changes of coupling constants in the Cu‐exchanged products, it was deduced that Zn4 and Zn3 are initially replaced, and then Zn1 and Zn2 are replaced later. The theoretical calculation further verified that Zn4 is replaced first, Zn3 next, then Zn1 and Zn2 last, and the coordination stability dominates the Cu/Zn exchange process. For the Ni/Zn and Co/Zn exchange processes, besides the coordination stability, the preferred coordination geometry was also considered in the stepwise‐exchange behavior. As Ni^II and Co^II ions especially favor octahedral coordination geometry in oxygen‐ligand fields, Ni^II ions and Co^II ions could only selectively exchange with the octahedral Zn^II ions, as was also confirmed by the experimental results. The stepwise metal‐exchange process occurs in a single crystal‐to‐single crystal fashion.     

Modification of D–A–π–A Configuration toward a High‐Performance Triphenylamine‐Based Sensitizer for Dye‐Sensitized Solar Cells: A Theoretical Investigation

In an attempt to shed light on how the addition of a benzothiadiazole (BTD) moiety influences the properties of dyes, a series of newly designed triphenylamine‐based sensitizers incorporating a BTD unit as an additional electron‐withdrawing group in a specific donor–acceptor–π‐acceptor architecture has been investigated. We found that different positions of the BTD unit provided significantly different responses for light absorption. Among these, it was established that the further the BTD unit is away from the donor part, the broader the absorption spectra, which is an observation that can be applied to improve light‐harvesting ability. However, when the BTD unit is connected to the anchoring group a faster, unfavorable charge recombination takes place; therefore, a thiophene unit was inserted between these two acceptors, providing redshifted absorption spectra as well as blocking unfavorable charge recombination. The results of our calculations provide valuable information and illustrate the potential benefits of using computation‐aided sensitizer design prior to further experimental synthesis.     

Predicting New Ugi–Smiles Couplings: A Combined Experimental and Theoretical Study

Following our previous mechanistic studies of multicomponent Ugi‐type reactions, theoretical calculations have been performed to predict the efficiency of new substrates in Ugi–Smiles couplings. First, as predicted, 2,4,6‐trichlorophenol experimentally gave the corresponding aryl‐imidate. Theoretical predictions of nitrosophenols as good acidic partners were then successfully confirmed by experiments. In the latter case, the reaction offers a new access to benzimidazoles.     

Gold‐Catalyzed Tandem Hydroamination/Formal Aza‐Diels–Alder Reaction of Homopropargyl Amino Esters: A Combined Computational and Experimental Mechanistic Study

A tandem gold‐catalyzed hydroamination/formal aza‐Diels–Alder reaction is described. This process, which employs quaternary homopropargyl amino ester substrates, leads to the formation of an intrincate tetracyclic framework and involves the generation of four bonds and five stereocenters in a highly diastereoselective manner. Theoretical calculations have allowed us to propose a suitable mechanistic rationalization for the tandem protocol. Additionally, by studying the influence of the ligands on the rate of the gold‐catalyzed reactions, it was possible to establish optimum conditions in which to perform the process with a variety of substituents on the amino ester substrates. Notably, the asymmetric version of the tandem reaction was also evaluated.     

Organic Chemistry of Graphene: The Diels–Alder Reaction

Herein, by using dispersion‐corrected density functional theory, we investigated the Diels–Alder chemistry of pristine and defective graphene. Three dienes were considered, namely 2,3‐dimethoxy‐1,3‐butadiene (DMBD), 9‐methylanthracene (9MA), and 9,10‐dimethylanthracene (910DMA). The dienophiles that were assayed were tetracyanoethylene (TCNE) and maleic anhydride (MA). When pristine graphene acted as the dienophile, we found that the cycloaddition products were 47–63 kcal mol^?1 less stable than the reactants, thus making the reaction very difficult. The presence of Stone–Wales translocations, 585 double vacancies, or 555‐777 reconstructed double vacancies did not significantly improve the reactivity because the cycloaddition products were still located at higher energy than the reactants. However, for the addition of 910DMA to single vacancies, the product showed comparable stability to the separated reactants, whereas for unsaturated armchair edges the reaction was extremely favorable. With regards the reactions with dienophiles, for TCNE, the cycloaddition product was metastable. In the case of MA, we observed a reaction product that was less stable than the reactants by 50 kcal mol^?1. For the reactions between graphene as a diene and the dienophiles, we found that the most‐promising defects were single vacancies and unsaturated armchair edges, because the other three defects were much‐less reactive. Thus, we conclude that the reactions with these above‐mentioned dienes may proceed on pristine or defective sheets with heating, despite being endergonic. The same statement also applies to the dienophile maleic anhydride. However, for TCNE, the reaction is only likely to occur onto single vacancies or unsaturated armchair edges. We conclude that the dienophile character of graphene is slightly stronger than its behavior as a diene.     

A Theoretical DFT‐Based and Experimental Study of the Transmetalation Step in Au/Pd‐Mediated Cross‐Coupling Reactions

In this work a combined theoretical and experimental investigation of the cross‐coupling reaction involving two metallic reaction centers, namely gold and palladium, is described. One metal center (Au) hereby is rather inert towards change in its oxidation state, whereas Pd undergoes oxidative insertion and reductive elimination steps. Detailed mechanistic and energetic studies of each individual step, with the focus on the key transmetalation step are presented and compared for different substrates and ligands on the catalytic Pd center. Different aryl halides (Cl, Br, I) and aryl triflates were investigated. Hereby the nature of the counteranion X turned out to be crucial. In the case of X=Cl and L=PMe₃ the oxidative addition is rate‐determining, whereas in the case of X=I the transmetalation step becomes rate‐determining in the Au/Pd‐cross‐coupling mechanism. A variety of Au–Pd transmetalation reaction scenarios are discussed in detail, favoring a transition state with short intermetallic Au–Pd contacts. Furthermore, without a halide counteranion the transmetalation from gold(I) to palladium(II) is highly endothermic, which confirms our experimental findings that the coupling does not occur with aryl triflates and similar weakly coordinating counteranions—a conclusion that is essential in designing new Au–Pd catalytic cycles. In combination with experimental work, this corrects a previous report in the literature claiming a successful coupling potentially catalytic in both metals with weakly coordinating counteranions.