Mechanistic Insights into Palladium‐Catalyzed Silylation of Aryl Iodides with Hydrosilanes through a DFT Study

The catalytic cycles of palladium‐catalyzed silylation of aryl iodides, which are initiated by oxidative addition of hydrosilane or aryl iodide through three different mechanisms characterized by intermediates R₃Si−Pd^II−H (Cycle A), Ar−Pd^II−I (Cycle B), and Pd^IV (Cycle C), have been explored in detail by hybrid DFT. Calculations suggest that the chemical selectivity and reactivity of the reaction depend on the ligation state of the catalyst and specific reaction conditions, including feeding order of substrates and the presence of base. For less bulky biligated catalyst, Cycle C is energetically favored over Cycle A, through which the silylation process is slightly favored over the reduction process. Interestingly, for bulky monoligated catalyst, Cycle B is energetically more favored over generally accepted Cycle A, in which the silylation channel is slightly disfavored in comparison to that of the reduction channel. Moreover, the inclusion of base in this channel allows the silylated product become dominant. These findings offer a good explanation for the complex experimental observations. Designing a reaction process that allows the oxidative addition of palladium(0) complex to aryl iodide to occur prior to that with hydrosilane is thus suggested to improve the reactivity and chemoselectivity for the silylated product by encouraging the catalytic cycle to proceed through Cycles B (monoligated Pd⁰ catalyst) or C (biligated Pd⁰ catalyst), instead of Cycle A.     

Asymmetric Synthesis of Silicon‐Stereogenic Silanes by Copper‐Catalyzed Desymmetrizing Protoboration of Vinylsilanes

The catalytic asymmetric creation of silanes with silicon stereocenters is a long‐sought but underdeveloped topic, and only a handful of examples have been reported. Moreover, the construction of chiral silanes containing (more than) two stereocenters is a more arduous task and remains unexploited. We herein report an unprecedented copper‐catalyzed desymmetrizing protoboration of divinyl‐substituted silanes with bis(pinacolato)diboron (B₂pin₂). This method enables the facile preparation of an array of enantiomerically enriched boronate‐substituted organosilanes bearing contiguous silicon and carbon stereocenters with exclusive regioselectivity and generally excellent diastereo‐ and enantioselectivity.     

Synthesis of Cyclooctatetraenes through a Palladium‐Catalyzed Cascade Reaction

Reported is a cascade reaction leading to fully substituted cyclooctatetraenes. This unexpected transformation likely proceeds through a unique 8π electrocyclization reaction of a ene triyne. DFT computations provide the mechanistic basis of this surprizing reaction.     

Design of a Highly Active Pd Catalyst with P,N Hemilabile Ligands for Alkoxycarbonylation of Alkynes and Allenes: A Density Functional Theory Study

In the palladium-catalysed methoxycarbonylation of technical propyne, the presence of propadiene poisons the hemilabile Pd(P,N) catalyst. According to density functional theory calculations (B3PW91-D3/PCM level), a highly stable π-allyl intermediate is the reason for this catalyst poisoning. Predicted regioselectivities suggest that at least 11 % of propadiene should yield this allyl intermediate, in which the reaction gets stalled under the turnover conditions due to an insurmountable methanolysis barrier of 25.8 kcal mol⁻¹. The results obtained for different ligands and substrates are consistent with the available experimental data. A new ligand, (6-Cl-3-Me-Py)PPh₂, is proposed, which is predicted to efficiently control the branched/linear selectivity, avoiding rapid poisoning (with only 0.2 % of propadiene being trapped as the Pd allyl complex), and to tremendously increase the catalytic activity by decreasing the overall barrier to 9.1 kcal mol⁻¹.     

Mechanistic Study of the Rhodium‐Catalyzed [3+2+2] Carbocyclization of Alkenylidenecyclopropanes with Alkynes

A systematic theoretical study has been performed on the recently reported Rh^I‐catalyzed [3+2+2] carbocyclization reactions between alkenylidenecyclopropanes (ACPs) and alkynes. With the aid of theoretical calculations, two possible mechanisms, that is, alkene‐carbometalation‐first and alkyne‐carbometalation‐first mechanisms, are examined in this study. In the oxidative addition step, the possibility of reaction on either the distal or proximal C? C bond of the cyclopropane group has been evaluated. The calculations indicate that the alkene‐activation‐first mechanism is more favored for the overall catalytic cycle. This mechanism involves four steps, that is, oxidative addition of the distal (rather than the proximal) C? C bond of cyclopropane group, alkene carbometalation, alkyne carbometalation, and reductive elimination. The rate‐determining step in the overall catalytic cycle is the carbometalation of the alkyne (i.e., the alkyne‐insertion step) and this step also determines the regioselectivity. Finally, the origin of the regioselectivity is determined by the steric effect (i.e., the steric crowding between the electron‐withdrawing group on alkyne and other ligands on the rhodium center) in the alkyne‐insertion step.     

Density Functional Study of Proline‐Catalyzed Intramolecular Baylis–Hillman Reactions

A rationalization of stereoselectivity : The mechanisms of proline‐catalyzed and imidazole‐co‐catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods. The computational data has allowed us to rationalize the experimental outcome, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path (see scheme).

     

Efficient Pd‐Catalyzed Allene Synthesis from Alkynes and Aryl Bromides through an Intramolecular Base‐Assisted Deprotonation (iBAD) Mechanism

An optimized ligand‐controlled palladium‐catalyzed allene synthesis starting from alkynes and aryl bromides giving rise to allene products in a simple and direct manner is described. The methodology is performed in an inter‐ and intramolecular fashion with unprecedented scope and excellent yields. Based on mechanistic investigations and on DFT calculations, the role played by the carboxylic additive (i.e., PivOH) in controlling the selectivity of the reaction is discussed, allowing us to propose an intramolecular base‐assisted deprotonation (iBAD) mechanism for this process.     

Palladium‐Catalyzed Cyclopropanation of Alkenyl Silanes by Diazoalkanes: Evidence for a Pd0 Mechanism

Pd ⁰ does the trick! Alkenyl silanes are efficiently cyclopropanated by diazoalkanes at low Pd loadings (see scheme). Clear evidence for the involvement of a Pd⁰ resting state for this reaction is given.

     

Desymmetrization‐Oriented Enantioselective Synthesis of Silicon‐Stereogenic Silanes by Palladium‐Catalyzed C−H Olefinations

A palladium‐catalyzed chelation‐assisted enantioselective C?H olefination of symmetrically diaryl‐substituted tetraorganosilicon derivatives was developed, enabling the generation of nitrogen‐containing silicon‐stereogenic tetraorganosilicon compounds with modest to good yields and good to excellent enantioselectivities (up to 95.5:4.5 e.r.). The Thorpe–Ingold effect exerted by the substituents on silicon was observed to have a profound influence on formation of olefinated products which were further converted into other relevant chiral organosilanes without the loss of enantiomeric purity, thus demonstrating the synthetic utility of the developed enantioselective olefination.     

On the Importance of Decarbonylation as a Side‐Reaction in the Ruthenium‐Catalysed Dehydrogenation of Alcohols: A Combined Experimental and Density Functional Study

We report a density functional study (B97‐D2 level) of the mechanism(s) operating in the alcohol decarbonylation that occurs as an important side‐reaction during dehydrogenation catalysed by [RuH₂(H₂)(PPh₃)₃]. By using MeOH as the substrate, three distinct pathways have been fully characterised involving either neutral tris‐ or bis‐phosphines or anionic bis‐phosphine complexes after deprotonation. α‐Agostic formaldehyde and formyl complexes are key intermediates, and the computed rate‐limiting barriers are similar between the various decarbonylation and dehydrogenation paths. The key steps have also been studied for reactions involving EtOH and iPrOH as substrates, rationalising the known resistance of the latter towards decarbonylation. Kinetic isotope effects (KIEs) were predicted computationally for all pathways and studied experimentally for one specific decarbonylation path designed to start from [RuH(OCH₃)(PPh₃)₃]. From the good agreement between computed and experimental KIEs (observed k_H/k_D=4), the rate‐limiting step for methanol decarbonylation has been ascribed to the formation of the first agostic intermediate from a transient formaldehyde complex.     

Mechanism and Selectivity of RuII‐ and RhIII‐Catalyzed Oxidative Spiroannulation of Naphthols and Phenols with Alkynes through a C−H Activation/Dearomatization Strategy

The ruthenium‐ and rhodium‐catalyzed oxidative spiroannulation of naphthols and phenols with alkynes was investigated by means of density functional theory calculations. The results show that the reaction undergoes O?H deprotonation/C(sp²)?H bond cleavage through a concerted metalation–deprotonation mechanism/migratory insertion of the alkyne into the M?C bond to deliver the eight‐membered metallacycle. However, the dearomatization through the originally proposed enol–keto tautomerization/C?C reductive elimination was calculated to be kinetically inaccessible. Alternatively, an unusual metallacyclopropene, generated from the isomerization of the eight‐membered metallacycle through rotation of the C?C double bond, was identified as a key intermediate to account for the experimental results. The subsequent C?C coupling between the carbene carbon atom and the carbon atom of the 2‐naphthol/phenol ring was calculated to be relatively facile, leading to the formation of the unexpected dearomatized products. The calculations reproduce quite well the experimentally observed formal [5+2] cycloaddition in the rhodium‐catalyzed oxidative annulation of 2‐vinylphenols with alkynes. The calculations show that compared with the case of 2‐alkenylphenols, the presence of conjugation effects and less steric repulsion between the phenol ring and the vinyl moiety make the competing reductive oxyl migration become dominant, which enables the selectivity switch from the spiroannulation to the formal [5+2] cycloaddition.     

Palladium‐Catalyzed Carbonylative Coupling of Aryl Iodides and Benzyl Acetylenes to 3‐Alkylidenefuran‐2‐ones under Mild Conditions and Its Density Functional Theory Modeling

A general and efficient method for the palladium‐catalyzed carbonylative coupling of aryl iodides to benzyl acetylenes has been developed. Various furanones have been prepared in excellent yields from their corresponding benzyl acetylenes at room temperature under a CO atmosphere. For aliphatic alkynes, their corresponding alkynones were obtained in good yields. Detailed DFT calculations have also been carried out to understand the reaction pathway and the most probable reaction mechanism has been proposed.     

Mechanism of the Asymmetric Autocatalytic Soai Reaction Studied by Density Functional Theory

The mechanism of the Soai reaction has been thoroughly investigated at the M05‐2X/6‐31G(d) level of theory, by considering ten energetically distinct paths. The study indicates the fully enantioselective catalytic cycle of the homochiral dimers to be the dominant mechanism. Two other catalytic cycles are shown to both be important for correct understanding of the Soai reaction. These are the catalytic cycle of the heterochiral dimer and the non‐enantioselective catalytic cycle of the homochiral dimers. The former has been proved to be not really competitive with the principal cycle, as required for the Soai reaction to manifest chiral amplification, whereas the latter, which is only slightly competitive with the principal one, nicely explains the experimental enantioselectivity observed in the reaction of 2‐methylpyrimidine‐5‐carbaldehyde. The study has also evidenced the inadequacy of the B3LYP functional for mechanistic investigations of the Soai reaction.     

Mechanistic Study on Oxorhenium‐Catalyzed Deoxydehydration and Allylic Alcohol Isomerization

The reaction mechanism of 1,2×n‐deoxydehydration (DODH; n=1, 2, 3 …) reactions with 1‐butanol as a reductant in the presence of methyltrioxorhenium(VII) catalyst has been investigated by DFT. The reduced rhenium compound, methyloxodihydroxyrhenium(V), serves as the catalytically relevant species in both allylic alcohol isomerization and subsequent DODH processes. Compared with three‐step pathway A, involving [1,3]‐transposition of allylic alcohols, direct two‐step pathway B is an alternative option with lower activation barriers. The rate‐limiting step of the DODH reaction is the first hydrogen transfer in methyltrioxorhenium(VII) reduction. Moreover, the increase in the distance between two hydroxyl groups in direct 1,2×n‐DODH reactions for C4 and C6 diols results in a higher barrier height.     

Conjugation‐Promoted Reaction of Open‐Cage Fullerene: A Density Functional Theory Study

Density functional theory calculations are performed to study the addition mechanism of e‐rich moieties such as triethyl phosphite to a carbonyl group on the rim of a fullerene orifice. Three possible reaction channels have been investigated. The obtained results show that the reaction of a carbonyl group on a fullerene orifice with triethyl phosphite most likely proceeds along the classical Abramov reaction; however, the classical product is not stable and is converted into the experimental product. An attack on a fullerene carbonyl carbon will trigger a rearrangement of the phosphate group to the carbonyl oxygen as the conversion transition state is stabilized by fullerene conjugation. This work provides a new insight on the reactivity of open‐cage fullerenes, which may prove helpful in designing new switchable fullerene systems.     

Enantioselective Arylation of N‐Tosylimines by Phenylboronic Acid Catalysed by a Rhodium/Diene Complex: Reaction Mechanism from Density Functional Theory

A DFT study of the reaction mechanism of the rhodium‐catalysed enantioselective arylation of (E)‐N‐propylidene‐4‐methyl‐benzenesulfonamide by phenylboronic acid [Lin et al J. Am. Chem. Soc.­ 2011 , 133, 12394] is reported. The catalyst ([{Rh(OH)(diene)}₂]) includes a chiral diene ligand and the reaction is conducted in 1,4‐dioxane in the presence of drying agents (4 Å molecular sieves). Because phenylboronic acid is in equilibrium with phenylboroxin and water under the reaction conditions, three catalytic cycles are proposed that differ in the way the transmetallation and the release of the product are brought about, depending on the availability of phenylboronic acid, water and boroxin in the reaction medium. Based on computations, a new mechanism for the title reaction is proposed, in which phenylboronic acid plays the double role of “aryl source” and proton donor. This path does not require the presence of adventitious water molecules, in keeping with a reaction conducted in a dry medium. Comparisons with the generally accepted mechanism for arylation of enones proposed by Hayashi and co‐workers (J. Am. Chem. Soc.­ 2002 , 124, 5052) show that the latter mechanism is less favourable and is not expected to operate in the case of the N‐tosylimine substrate considered herein. Finally, the possibility that phenylboroxin is the aryl source has also been investigated, but is not found to be competitive.     

Unexpected Anion Effect in the Alkoxylation of Alkynes Catalyzed by N‐Heterocyclic Carbene (NHC) Cationic Gold Complexes

The intermolecular alkoxylation of alkynes is the oldest application of cationic gold(I) catalysts; however, no systematic experimental data about the role of the anion are available. In this contribution, the role of the anion in this catalytic reaction as promoted by a N‐heterocyclic carbene‐based gold catalyst, [(NHC)AuX] (X=BARF^?, BF₄^?, OTf^?, OTs^?, TFA^?, or OAc^?) is analyzed, through a combined experimental (NMR spectroscopy) and theoretical (DFT calculation) approach. The most important factor seems to be the ability to abstract the proton from the methanol during the nucleophilic attack, and such ability is related to the anion basicity. On the other hand, too high coordination power or basicity of the anion worsens the catalytic performance by preventing alkyne coordination or by forming too much free methoxide in solution, which poisons the catalyst. The intermediate coordinating power and basicity of the OTs^? anion provides the best compromise to achieve efficient catalysis.     

Mechanism of Alkyne Alkoxycarbonylation at a Pd Catalyst with P,N Hemilabile Ligands: A Density Functional Study

A detailed mechanism for alkyne alkoxycarbonylation mediated by a palladium catalyst has been characterised at the B3PW91‐D3/PCM level of density functional theory (including bulk solvation and dispersion corrections). This transformation, investigated via the methoxycarbonylation of propyne, involves a uniquely dual role for the P,N hemilabile ligand acting co‐catalytically as both an in situ base and proton relay coupled with a Pd⁰ centre, allowing for surmountable barriers (highest ΔG^≠ of 22.9 kcal mol^?1 for alcoholysis). This proton‐shuffle between methanol and coordinated propyne accounts for experimental requirements (high acid concentration) and reproduces observed regioselectivities as a function of ligand structure. A simple ligand modification is proposed, which is predicted to improve catalytic turnover by three orders of magnitude.