Density functional theory (DFT) calculations (B3LYP and M06) have been utilized to study a newly reported Heck-type reaction that uses an allylic or alkenyl alcohol as substrate and palladium as ...catalyst in the form of a chelate with a chiral pyridine oxazoline (PyrOx) ligand. The reaction not only controls the regio- and enantioselectivities of arylation of the CC bond, but also forms the carbonyl functionality up to four bonds away from the aryl substituent via tandem CC bond migration and enol-to-keto conversion. Computations performed on representative reaction systems allow us to propose a detailed mechanism with several key steps. Initial oxidation of palladium(0) by aryldiazonium generates active arylpalladium(II) species that bind the CC bond of an allylic or alkenyl alcohol. The activated CC bond inserts into the palladium–aryl moiety to attain aryl substitution and a chiral carbon center, and the resulting complex undergoes β-hydride elimination to give a new CC bond that can repeat the insertion/elimination process to move down the carbon chain to form an enol that tautomerizes to a highly stable carbonyl final product. The calculations reveal that the CC bond migratory insertion step determines both the regioselectivity and the enantioselectivity of arylation, with the former arising mainly from the electronic effect of the hydroxyl group on the charge distribution over the CC bond and the latter originating from a combination of steric repulsion, trans influence, and C–H/π dispersion interactions.
The Ni‐catalyzed decarbonylative borylation of (hetero)aryl carboxylic acids with B2cat2 has been achieved without recourse to any additives. This Ni‐catalyzed method exhibits a broad substrate scope ...covering poorly reactive non‐ortho‐substituted (hetero)aryl carboxylic acids, and tolerates diverse functional groups including some of the groups active to Ni0 catalysts. The key to achieve this decarbonylative borylation reaction is the choice of B2cat2 as a coupling partner that not only acts as a borylating reagent, but also chemoselectively activates aryl carboxylic acids towards oxidative addition of their C(acyl)−O bond to Ni0 catalyst via the formation of acyloxyboron compounds. A combination of experimental and computational studies reveals a detailed plausible mechanism for this reaction system, which involves a hitherto unknown concerted decarbonylation and reductive elimination step that generates the aryl boronic ester product. This mode of boron‐promoted carboxylic acid activation is also applicable to other types of reactions.
A Ni‐catalyzed direct decarbonylative borylation of aryl carboxylic acids with B2cat2 has been established. B2cat2 serves as a borylating agent, but also activates the carboxylic acid substrate towards decarbonylative coupling, playing a dual role in this reaction. A combination of experimental and computational studies reveals that the reaction proceeds through a hitherto unknown concerted decarbonylation and reductive elimination step.
There is continued interest in developing new Pd-catalyzed cross-coupling reactions. This density functional theory (DFT) study explores the detailed workings of a notable base-free cross-coupling ...reaction of vinyl carboxylates with arylboronic acids at ambient conditions enabled by Pd(OAc)2 along with a phosphine ligand. Extensive DFT calculations have been performed on the proposed Pd(II)-only mechanism and other possibilities, suggesting that the reaction preferably proceeds by a Pd(0)/Pd(II) pathway with an intricate Pd(0)-generating process. Two consecutive transmetalations with phenylboronic acid lead to a diphenyl-Pd(II) phosphine intermediate, which would undergo a phenyl–phenyl reductive elimination rather than a redox-neutral carbopalladation. The resulting Pd(0) phosphine species introduces a Pd(0)/Pd(II) catalytic cycle involving the key elementary steps of oxidative addition, transmetalation, and reductive elimination. The oxidative addition of the vinyl carboxylate to Pd(0) via R–OAc bond cleavage is the rate-determining step. The dual role of an arylboronic acid as a reducing agent and coupling partner in Pd-catalyzed cross-coupling reactions has been elucidated for the first time. This and other mechanistic insights gained can have implications for new reaction development.
We report the first computational study on a nickel hydride HAT-initiated catalytic reaction, a novel hydrodefluorination of CF3-substituted aryl alkenes to afford gem-difluoroalkenes. This study ...provides detailed mechanistic insights into the reaction, including HAT from NiH to C=C, a carbon radical rebound to nickel to facilitate chemoselective defluorination, and a two-state reactivity of Ni(ii) enabling σ-bond metathesis with PhSiH3 to regenerate the catalyst. The findings can have implications for developing new metal hydride HAT-initiated reactions.
The hydroformylation reaction is used on a large industrial scale to convert olefins and synthesis gas (CO + H2) into aldehydes. Researchers have recently discovered that a class of cationic Co(II) ...complexes of the formula CoII(PP)(acac)+ (PP = diphosphine, acac = acetylacetonate) can catalyze hydroformylation with activity approaching that of the widely used rhodium catalysts (Hood, D. M. et al. Science 2020, 367, 542−548 ). This density functional theory (DFT) study reveals the detailed workings of the cationic Co(II) catalyst system. The precatalyst CoII(PP)(acac)+ is initiated by reacting with H2 and CO to generate active species HCoII(CO)2(PP)+. In comparison with the 18-electron neutral Co(I) catalytic species HCoI(CO)3(PR3), these cationic Co(II) species, with their unique 17-electron and square pyramidal structure, invoke a lower-energy pathway through different elementary steps such as associative alkene uptake and heterolytic H2 cleavage. The regioselectivity for linear aldehyde products is due to a combination of electronic and steric effects that favor the anti-Markovnikov insertion of a terminal alkene into the Co–H bond. DFT calculations predict that addition of PMe3 would facilitate the precatalyst initiation, thereby decreasing the reaction temperature or shortening the induction period. The insights gained by this theoretical study can be useful for the further development of hydroformylation catalysts.
We report the first computational study on a nickel hydride HAT-initiated catalytic reaction, a novel hydrodefluorination of CF 3 -substituted aryl alkenes to afford gem -difluoroalkenes. This study ...provides detailed mechanistic insights into the reaction, including HAT from NiH to CC, a carbon radical rebound to nickel to facilitate chemoselective defluorination, and a two-state reactivity of Ni( ii ) enabling σ-bond metathesis with PhSiH 3 to regenerate the catalyst. The findings can have implications for developing new metal hydride HAT-initiated reactions.
This work illustrates the reductive coupling of electron-rich aryl halides with tertiary alkyl halides under Ni-catalyzed cross-electrophile coupling conditions, which offers an efficient protocol ...for the construction of all carbon quaternary stereogenic centers. The mild and easy-to-operate reaction tolerates a wide range of functional groups. The utility of this method is manifested by the preparation of cyclotryptamine derivatives, wherein successful incorporation of 7-indolyl moieties is of particular interest as numerous naturally occurring products are composed of these key scaffolds. DFT calculations have been carried out to investigate the proposed radical chain and double oxidative addition pathways, which provide useful mechanistic insights into the part of the reaction that takes place in solution.
Deoxygenative radical C–C bond-forming reactions of alcohols are a long-standing challenge in synthetic chemistry, and the current methods rely on multistep procedures. Herein, we report a direct ...dehydroxylative radical alkylation reaction of tertiary alcohols. This new protocol shows the feasibility of generating tertiary carbon radicals from alcohols and offers an approach for the facile and precise construction of all-carbon quaternary centers. The reaction proceeds with a broad substrate scope of alcohols and activated alkenes. It can tolerate a wide range of electrophilic coupling partners, including allylic carboxylates, aryl and vinyl electrophiles, and primary alkyl chlorides/bromides, making the method complementary to the cross-coupling procedures. The method is highly selective for the alkylation of tertiary alcohols, leaving secondary/primary alcohols (benzyl alcohols included) and phenols intact. The synthetic utility of the method is highlighted by its 10-g-scale reaction and the late-stage modification of complex molecules. A combination of experiments and density functional theory calculations establishes a plausible mechanism implicating a tertiary carbon radical generated via Ti-catalyzed homolysis of the C–OH bond.
This work emphasizes easy access to α-vinyl and aryl amino acids
Ni-catalyzed cross-electrophile coupling of bench-stable
-carbonyl-protected α-pivaloyloxy glycine with vinyl/aryl halides and ...triflates. The protocol permits the synthesis of α-amino acids bearing hindered branched vinyl groups, which remains a challenge using the current methods. On the basis of experimental and DFT studies, simultaneous addition of glycine α-carbon (Gly) radicals to Ni(0) and Ar-Ni(ii) may occur, with the former being more favored where oxidative addition of a C(sp
) electrophile to the resultant Gly-Ni(i) intermediate gives a key Gly-Ni(iii)-Ar intermediate. The auxiliary chelation of the
-carbonyl oxygen to the Ni center appears to be crucial to stabilize the Gly-Ni(i) intermediate.
DFT computations reveal different reaction mechanisms for the oxidative addition of C(sp
2
)-F and C(sp
3
)-F bonds to the Al(
i
) complexes: a concerted mechanism for C(sp
2
)-F and a stepwise ...mechanism for C(sp
3
)-F involving fluoride transfer and the formation and recombination of an ion pair.
DFT computations reveal different reaction mechanisms for the oxidative addition of C(sp
2
)-F and C(sp
3
)-F bonds to the Al(
i
) complexes: a concerted mechanism for C(sp
2
)-F and a stepwise mechanism for C(sp
3
)-F involving fluoride transfer and the formation and recombination of an ion pair.
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