A Thorough DFT Study of the Mechanism of Homodimerization of Terminal Olefins through Metathesis with a Chelated Ruthenium Catalyst: From Initiation to <i>Z</i> Selectivity to Regeneration

Density functional theory (DFT) calculations (B3LYP, M06, and M06-L) have been performed to investigate the mechanism and origins of <i>Z</i> selectivity of the metathesis homodimerization of terminal olefins catalyzed by chelated ruthenium complexes. The chosen system is, without any simplification, the experimentally performed homocoupling reaction of 3-phenyl-1-propene with <b>1cat</b>, a pivalate and N-heterocyclic carbene (NHC) chelated Ru precatalyst. The six-coordinate <b>1cat</b> converts to a trigonal-bipyramidal intermediate (<b>3</b>) through initial dissociation and isomerization. The metathesis reaction of complex <b>3</b> with 3-phenyl-1-propene occurs in a side-bound mechanism and generates the trigonal-bipyramidal Ru–benzylidene complex <b>6</b>. Complex <b>6</b> is the active catalyst for the subsequent side-bound metathesis with 3-phenyl-1-propene, which forms metallacyclobutanes that lead to the (<i>Z</i>)- and (<i>E</i>)-olefin homodimers. The transition states of cycloreversion leading to the (<i>Z</i>)- and (<i>E</i>)-olefins differ in energy by 2.2 kcal/mol, which gives rise to a calculated <i>Z</i> selectivity that agrees with experimental results. The <i>Z</i> selectivity stems from reduced steric repulsion in the transition state. The regeneration of complex <b>6</b> occurs along with the formation of the gaseous byproduct ethylene, whose evolution drives the overall reaction. As our results indicate, the chelating ligands are crucial for this new class of Ru catalysts to achieve <i>Z</i>-selective olefin metathesis, because they direct olefin attack, differentiate energies of the transition states and intermediates, and support the complexes in certain coordination geometries

Does the Ruthenium Nitrato Catalyst Work Differently in <i>Z</i>‑Selective Olefin Metathesis? A DFT Study

In the new class of N-heterocyclic carbene (NHC) chelated ruthenium catalysts for <i>Z</i>-selective olefin metathesis, the nitrato-supported complex <b>3cat</b> appears distinct from all the other carboxylato-supported analogues. We have performed DFT calculations (B3LYP and M06) to elucidate the mechanism of <b>3cat</b>-catalyzed metathesis homodimerization of 3-phenyl-1-propene. The six-coordinate <b>3cat</b> transforms via initial dissociation and isomerization into a trigonal-bipyramidal intermediate (<b>5</b>), from which two consecutive metathesis reactions via the side-bound mechanism lead to (<i>Z</i>)-PhCH₂CHCHCH₂Ph (major) and (<i>E</i>)-PhCH₂CHCHCH₂Ph (minor). In the overall mechanism, <b>3cat</b> functions similarly to the pivalate-supported analogue <b>1cat</b>. The substitution of a smaller nitrato group does not change the side-bound olefin attack mechanism for either the initiation or homocoupling metathesis. The chelation of the NHC ligand causes this class of Ru catalysts to favor the side-bound over the bottom-bound mechanism. The calculated energetics corroborate the experimental observation that <b>3cat</b> is somewhat more active than <b>1cat</b> in catalyzing the homodimerization of 3-phenyl-1-propene

DFT Mechanistic Study of Functionalizations of ω‑Ene-Cyclopropanes and Alkylidenecyclopropanes via Allylic C–H and C–C Bond Cleavage Facilitated by a Zirconocene Complex

A DFT mechanistic study has been performed to understand the [Zr]­C₄H₈ (Zr = ZrCp₂)-mediated transformations of ω-ene-cyclopropane (ω-ene-CP) and alkylidenecyclopropane (ACP) to acyclic compounds. The transformations proceed via allylic C–H bond activation, hydride transfer, C–C bond cleavage of the three-membered ring, and additions of electrophiles. The energetic results indicate that, among the possible pathways, the one leading to the experimental products is most energetically favorable, rationalizing the selectivity of the reactions. The Zr-walk takes place via allylic C–H bond activation followed by hydride transfer, completing a 1,3-hydrogen transfer. In comparison, the Pd-walk involved in the Pd-catalyzed Heck-type relay coupling reactions proceeds via migratory insertion followed by β-H elimination, resulting in a 1,2-hydrogen transfer. The difference is due to the fact that the [Zr] active species does not have a Zr–H or Zr–C bond for CC bond migratory insertion, while the Pd–H or Pd–C bond in [Pd] active intermediates enables such an insertion. In addition, the preference of Pd­(II) over Pd­(IV) disfavors the allylic C–H bond activation involved in the Zr-walk process. We further explored if the three-membered ring in the ω-ene-CP and ACP could be enlarged to four- or five-membered rings for similar transformations. The energetic results indicate that it is promising to enlarge a three-membered to a four-membered ring, but the extension to a five-membered ring is inferior because of the endergonic ring-opening with somewhat high barrier

Mechanism and Origins of <i>Z</i> Selectivity of the Catalytic Hydroalkoxylation of Alkynes via Rhodium Vinylidene Complexes To Produce Enol Ethers

We report the first theoretical study of transition-metal-catalyzed hydroalkoxylation of alkynes to produce enol ethers. The study utilizes density functional theory calculations (M06) to elucidate the mechanism and origins of <i>Z</i> selectivity of the anti-Markovnikov hydroalkoxylation of terminal alkynes with a Rh­(I) 8-quinolinolato carbonyl chelate (<b>1cat</b>). The chosen system is, without any truncation, the realistic reaction of phenylacetylene and methanol with <b>1cat</b>. Initiation of <b>1cat</b> through phenylacetylene substitution for carbonyl generates the active catalyst, a Rh­(I) η²-alkyne complex (<b>3</b>), which tautomerizes via an indirect 1,2-hydrogen shift to the Rh­(I) vinylidene complex <b>4</b>. The oxygen nucleophile methanol attacks the electrophilic vinylidene C_α, forming two stereoisomeric Rh­(I) vinyl complexes (<b>15</b> and <b>16</b>), which ultimately lead to the (<i>Z</i>)- and (<i>E</i>)-enol ether products. These complexes undergo two ligand-mediated proton transfers to yield Rh­(I) Fischer carbenes, which rearrange through a 1,2-β-hydrogen shift to afford complexes with π-bound product enol ethers. Final substitution of phenylacetylene gives (<i>Z</i>)- and (<i>E</i>)-PhCHCHOMe and regenerates <b>3</b>. The anti-Markovnikov regioselectivity stems from the Rh­(I) vinylidene complex <b>4</b> with reversed C_α and C_β polarity. The stereoselectivity arises from the turnover-limiting transition states (TSs) for the Rh­(I) carbene rearrangement: the <i>Z</i>-product-forming <b>TS24</b> is sterically less congested and hence more stable than the <i>E</i>-product-forming <b>TS25</b>. The difference in energy (1.2 kcal/mol) between <b>TS24</b> and <b>TS25</b> gives a theoretical <i>Z</i> selectivity that agrees well with the experimental value. Calculations were also performed on the key TSs of reactions involving two other alkyne substrates, and the results corroborate the proposed mechanism. The findings taken together give an insight into the roles of the rhodium–quinolinolato chelate framework in directing phenylacetylene attack by trans effect, mediating hydrogen transfers through hydrogen bonding, and differentiating the energies of key TSs by steric repulsion

How Does an Earth-Abundant Copper-Based Catalyst Achieve Anti-Markovnikov Hydrobromination of Alkynes? A DFT Mechanistic Study

The first catalytic hydrohalogenation of alkynes was recently achieved using a copper­(I) N-heterocyclic carbene (NHC) complex, and the reaction was found to be syn and anti-Markovnikov selective. The present work is a density functional theory (DFT) computational study (B3LYP and M06) on the detailed mechanism of this remarkable catalytic reaction. The reaction begins with a phenoxide additive turning over the precatalyst (NHC)­CuCl into (NHC)­Cu­(OAr), which subsequently transmetalates with the hydride source Ph₂SiH₂ to deliver the copper­(I) hydride complex (NHC)­CuH. (NHC)­CuH undertakes hydrocupration of the substrate RCCH via alkyne coordination and subsequent migratory insertion into the Cu–H bond, forming (<i>E</i>)-(NHC)­Cu­(CHCHR). The migratory insertion step determines the syn selectivity because it occurs by a concerted pathway, and it also determines the anti-Markovnikov regioselectivity that arises from the charge distributions across the Cu–H and CC bonds. The brominating agent (BrCl₂C)₂ uses the bromonium end to attack the Cu-bound vinylic carbon atom of (<i>E</i>)-(NHC)­Cu­(CHCHR), leading to the final (<i>E</i>)-alkenyl bromide product (<i>E</i>)-RHCCHBr, as well as the copper­(I) alkyl complex (NHC)­Cu­(CCl₂CBrCl₂), which undergoes β-bromide elimination to give the catalyst precursor (NHC)­CuBr for the next cycle. (NHC)­CuBr reacts with the phenoxide to regenerate the active catalyst (NHC)­Cu­(OAr). The computational results rationalize the experimental observations, reveal new insights into the mechanism of the Cu­(I)-catalyzed hydrobromination of alkynes, and have implications for other catalytic functionalization reactions of alkynes involving active [Cu]–H intermediates

How Does an Earth-Abundant Copper-Based Catalyst Achieve Anti-Markovnikov Hydrobromination of Alkynes? A DFT Mechanistic Study

The first catalytic hydrohalogenation of alkynes was recently achieved using a copper­(I) N-heterocyclic carbene (NHC) complex, and the reaction was found to be syn and anti-Markovnikov selective. The present work is a density functional theory (DFT) computational study (B3LYP and M06) on the detailed mechanism of this remarkable catalytic reaction. The reaction begins with a phenoxide additive turning over the precatalyst (NHC)­CuCl into (NHC)­Cu­(OAr), which subsequently transmetalates with the hydride source Ph₂SiH₂ to deliver the copper­(I) hydride complex (NHC)­CuH. (NHC)­CuH undertakes hydrocupration of the substrate RCCH via alkyne coordination and subsequent migratory insertion into the Cu–H bond, forming (<i>E</i>)-(NHC)­Cu­(CHCHR). The migratory insertion step determines the syn selectivity because it occurs by a concerted pathway, and it also determines the anti-Markovnikov regioselectivity that arises from the charge distributions across the Cu–H and CC bonds. The brominating agent (BrCl₂C)₂ uses the bromonium end to attack the Cu-bound vinylic carbon atom of (<i>E</i>)-(NHC)­Cu­(CHCHR), leading to the final (<i>E</i>)-alkenyl bromide product (<i>E</i>)-RHCCHBr, as well as the copper­(I) alkyl complex (NHC)­Cu­(CCl₂CBrCl₂), which undergoes β-bromide elimination to give the catalyst precursor (NHC)­CuBr for the next cycle. (NHC)­CuBr reacts with the phenoxide to regenerate the active catalyst (NHC)­Cu­(OAr). The computational results rationalize the experimental observations, reveal new insights into the mechanism of the Cu­(I)-catalyzed hydrobromination of alkynes, and have implications for other catalytic functionalization reactions of alkynes involving active [Cu]–H intermediates

Mechanistic Insight into Ketone α‑Alkylation with Unactivated Olefins via C–H Activation Promoted by Metal–Organic Cooperative Catalysis (MOCC): Enriching the MOCC Chemistry

Metal–organic cooperative catalysis (MOCC) has been successfully applied for hydroacylation of olefins with aldehydes via directed C­(sp²)–H functionalization. Most recently, it was reported that an elaborated MOCC system, containing Rh­(I) catalyst and 7-azaindoline (<b>L1</b>) cocatalyst, could even catalyze ketone α-alkylation with unactivated olefins via C­(sp³)–H activation. Herein we present a density functional theory study to understand the mechanism of the challenging ketone α-alkylation. The transformation uses IMesRh­(I)­Cl­(<b>L1</b>)­(CH₂CH₂) as an active catalyst and proceeds via sequential seven steps, including ketone condensation with <b>L1</b>, giving enamine <b>1b</b>; <b>1b</b> coordination to Rh­(I) active catalyst, generating Rh­(I)–<b>1b</b> intermediate; C­(sp²)–H oxidative addition, leading to a Rh­(III)–H hydride; olefin migratory insertion into Rh­(III)–H bond; reductive elimination, generating Rh­(I)–<b>1c</b>(alkylated <b>1b</b>) intermediate; decoordination of <b>1c</b>, liberating <b>1c</b> and regenerating Rh­(I) active catalyst; and hydrolysis of <b>1c</b>, furnishing the final α-alkylation product <b>1d</b> and regenerating <b>L1</b>. Among the seven steps, reductive elimination is the rate-determining step. The C–H bond preactivation via agostic interaction is crucial for the bond activation. The mechanism rationalizes the experimental puzzles: why only <b>L1</b> among several candidates performed perfectly, whereas others failed, and why Wilkinson’s catalyst commonly used in MOCC systems performed poorly. Based on the established mechanism and stimulated by other relevant experimental reactions, we attempted to enrich MOCC chemistry computationally, exemplifying how to develop new organic catalysts and proposing <b>L7</b> to be an alternative for <b>L1</b> and demonstrating the great potential of expanding the hitherto exclusive use of Rh­(I)/Rh­(III) manifold to Co(0)/Co­(II) redox cycling in developing MOCC systems

Depolymerization of Oxidized Lignin Catalyzed by Formic Acid Exploits an Unconventional Elimination Mechanism Involving 3c–4e Bonding: A DFT Mechanistic Study

A DFT study has been performed to gain insight into the formic-acid-catalyzed depolymerization of the oxidized lignin model (<b>1</b>^<b>ox</b>) to monoaromatics, developed by Stahl <i>et al.</i> (<i>Nature</i> <b>2014</b>, <i>515</i>, 249–252). The conversion proceeds sequentially via formylation, elimination, and hydrolysis. Intriguingly, the elimination process exploits an unconventional mechanism different from the known ones such as E2 and E1cb. The new mechanism is characterized by passing through an intermediate stabilized by a proton-shared 3c–4e bond (HCOO^⊖···H^⊕···^⊖OC^α) and by shifting the 3c–4e bond to the 3c–4e HCOO^⊖···H^⊕···^⊖OOCH bond in the joint leaving group that is originally a regular H-bond (HCOO–H···OOCH−). According to these characteristics, as well as the important role of the original HCOO–H···OOCH– bond, we term the mechanism as E1H-3c4e elimination. The root-cause of the E1H-3c4e elimination is that the poor leaving formate group is less competitive in stabilizing the negative charge resulted from H^β abstraction by the HCOO^– base than the nearby carbonyl group (C^αO) that can utilize the negative charge to form a stabilizing 3c–4e bond with a formic acid molecule. In addition, the study characterizes versatile roles of formic acid in achieving the whole transformation, which accounts for why the HCO₂H/NaCO₂H medium works so elegantly for <b>1</b>^<b>ox</b> depolymerizaion

DFT Mechanistic Study of Ru^II-Catalyzed Amide Synthesis from Alcohol and Nitrile Unveils a Different Mechanism for Borrowing Hydrogen

Using Ru^II complex as a mediator, Hong and co-workers recently developed a redox-neutral synthetic strategy to produce amide from primary alcohol and nitrile with complete atom economy. Intrigued by the novel strategy, we performed DFT computations to unravel the catalytic mechanism of the system. The transformation is catalyzed by Ru^IIH₂(CO)­(PPh₃)­(IⁱPr) (IⁱPr = 1,2-diisopropylimidazol-2-ylidene) via four stages including nitrile reduction, alcohol dehydrogenation, C–N coupling, and amide production. Generally, alcohol dehydrogenation in dehydrogenative coupling (DHC) or borrowing hydrogen methodology (BHM) takes place separately, transferring the H^α and hydroxyl H^OH atoms of alcohol to the catalyst to form the catalyst-H₂ hydride. Differently, the alcohol dehydrogenation in the present system couples with nitrile hydrogenation; alcohol plays a reductant role to aid nitrile reduction by transferring its H^OH to nitrile N atom directly and H^α to the catalyst and meanwhile becomes partially oxidized. In our proposed preferred mechanism-B, the Ru^II state of the catalyst is retained in the whole catalytic cycle. Mechanism-A, postulated by experimentalists, involves Ru^II → Ru⁰ → Ru^II oxidation state alternation, and the Ru⁰ intermediate is used to dehydrogenate alcohol separately via oxidative addition, followed by β-hydride elimination. As a result, mechanism-B is energetically more favorable than mechanism-A. In mechanism-B, the (N-)H atom of the amide bond exclusively originates from the hydroxyl H^OH of alcohol. In comparison, the (N-)­H atom in mechanism-A stems from either H^OH or H^α of alcohol. The way of borrowing hydrogen that is used by nitrile is via participating in alcohol dehydrogenation, which is different from that in the conventional DHC/BHM reactions and may help expand the strategy and develop new routes for utilizing DHC and BHM strategies

Mechanism of <i>Z</i>‑Selective Olefin Metathesis Catalyzed by a Ruthenium Monothiolate Carbene Complex: A DFT Study

A ruthenium monothiolate carbene complex (<b>2cat</b>) readily derived from the Grubbs–Hoveyda system is among the newly developed catalysts for <i>Z</i>-selective olefin metathesis reactions. We have performed density functional theory calculations (B3LYP and M06) to elucidate the detailed mechanism of <b>2cat</b>-catalyzed homometathesis of terminal olefins. The five-coordinate <b>2cat</b> dissociates to a tetrahedral intermediate, from which two consecutive metathesis events via the bottom-bound olefin attack mechanism lead to (<i>Z</i>)-olefins as major products. The <i>Z</i> selectivity stems from the bulky thiolate ligand, which sterically forces both olefinic substituents to the far side of the metallacyclobutane ring to achieve a <i>Z</i> geometry in the resulting olefin product