Ligand-controlled Selectivity Research Articles

Recent Advances in Ligand-Controlled Regio- or Stereodivergent Transition-Metal-Catalyzed Hydroelementation (H[E]) (E = H, B, Si, Ge) of C–C Unsaturated Systems

AbstractReductive functionalization of C–C unsaturated systems, including alkenes and alkynes, with a range of hydroelements (H[E]) is one of the most fundamental and highly practical methods for the synthesis of functionalized hydrocarbons. Since the resultant hydrocarbon products have strong applicability as synthetic intermediates, numerous homogeneous organo(metallic) catalysts have been intensively utilized to date for reductive functionalization reactions. In particular, well-defined transition-metal-based catalysts capable of controlling the regio- or stereoselectivity of a product by harnessing the addition of H[E] (E = H, B, Si, Ge) into Cα–Cβ unsaturated bonds have drawn special attention. In this review, we describe recent examples of transition-metal catalytic systems (M = Fe, Co, Rh, Pd, Ni) for regio- or stereodivergent hydroelementation reactions of (conjugated) alkenes, alkynes, and allenes to give a pair of isomeric products in high selectivities from the same starting compounds simply by variation of the ligand. Mechanistic aspects of the ligand-controlled selectivity divergence are discussed in detail on the basis of experimental observations and/or computational insights.1 Introduction2 Hydroelementation of Alkenes and Alkynes3 Hydroelementation of Conjugated Dienes and Diynes4 Hydroelementation of Allenes5 Summary and Outlook

Nickel-catalyzed skeletal transformation of tropone derivatives via C-C bond activation: catalyst-controlled access to diverse ring systems.

We report herein on nickel-catalyzed carbon–carbon bond cleavage reactions of 2,4,6-cycloheptatrien-1-one (tropone) derivatives. When a Ni/N-heterocyclic carbene catalyst is used, decarbonylation proceeds with the formation of a benzene ring, while the use of bidentate ligands in conjunction with an alcohol additive results in a two-carbon ring contraction with the generation of cyclopentadiene derivatives. The latter reaction involves a nickel–ketene complex as an intermediate, which was characterized by X-ray crystallography. The choice of an appropriate ligand allows for selective synthesis of four different products via the cleavage of a seven-membered carbocyclic skeleton. Reaction mechanisms and ligand-controlled selectivity for both types of ring contraction reactions were also investigated computationally.

Ligand-Controlled Selectivity in the Pd-Catalyzed C–H/C–H Cross-Coupling of Indoles with Molecular Oxygen

Two indoles linked by a C–C bond have recently emerged as promising scaffolds in medicinal chemistry. Their synthesis, however, involves a multitude of reaction steps. So far, the direct C–H/C–H cr...

A computational study of isoprene polymerization catalyzed by iminopyridine-supported iron complexes: Ligand-controlled selectivity

DFT calculations have been conducted for investigating the relation between the electronic states and catalytic properties of iminopyridine-ligated cationic iron complexes in the stereoselective polymerization of isoprene. Iminopyridine ligand is found to be redox-inert in this catalytic system. The neutral pre-catalyst and active cationic species present as a high spin quintet and the open-shell unpaired 3d-electrons reside on Fe center. The trans and cis polymerization of isoprene catalyzed by the complexes [(octyl-iminopyridine)FeII(Me)]+ (A1) and [(supermesityl-iminopyridine)FeII(Me)]+ (A2) could be attributed to the electronic and steric effects in the transition states, respectively.

Recent advances in theoretical studies on ligand-controlled selectivity of nickel- and palladium-catalyzed cross-coupling reactions

Nickel- and palladium-catalyzed cross-coupling reactions have attracted wide attentions, while ligand-controlled selectivity in these reactions are still elusive, and calculations can help obtain possible catalytic cycles to generate different products and provide insights into key factors of selectivity, which facilitates the development of new catalyst systems to control reaction selectivity. This review covers our efforts and some significant achievements from other groups on ligand-controlled reaction selectivity of coupling reactions, including introduction, computational methods, selectivity control by ligands in Ni- and Pd-catalyzed coupling reactions, as well as summary and future perspectives.

N-Heterocyclic Carbene Ligand-Controlled Chemodivergent Suzuki–Miyaura Cross Coupling

Two N-heterocyclic carbene ligands provide orthogonal chemoselectivity during the Pd-catalyzed Suzuki-Miyaura (SM) cross-coupling of chloroaryl triflates. The use of SIPr [SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene] leads to selective cross-coupling at chloride, while the use of SIMes [SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene] provides selective coupling at triflate. With most chloroaryl triflates and arylboronic acids, ligand-controlled selectivity is high (≥10:1). The scope of this methodology is significantly more general than previously reported methods for selective SM coupling of chloroaryl triflates using phosphine ligands. Density functional theory studies suggest that palladium's ligation state during oxidative addition is different with SIMes compared to SIPr.

DFT studies on mechanistic origins of ligand-controlled selectivity in Pd-catalyzed non-decarbonylative and decarbonylative reductive conversion of acyl fluoride.

The mechanisms and origins for ligand-controlled non-decarbonylative and decarbonylative conversions of acyl fluorides catalyzed by palladium catalysts with different ligands tricyclohexylphosphine (PCy3) and 1,2-bis(dicyclohexylphosphino)ethane (DCPE) have been investigated by density functional theory (DFT) calculations. In the case of the DCPE ligand, the favorable catalytic cycle contains four steps, oxidative addition, decarbonylation, transmetallation and reductive elimination. In the case of the PCy3 ligand, the favorable catalytic cycle proceeds by three steps, oxidative addition, transmetallation and reductive elimination. Distortion/interaction analysis indicated that decarbonylation does not occur for PCy3 owing to the repulsive interaction between PCy3 and substrates. Present calculations agree with the experimental observations and understanding these surprising ligand-controlled non-decarbonylative and decarbonylative selectivity reactions could provide important insights into the development of selective catalyst systems.

Pd-Catalyzed Divergent C(sp2)-H Activation/Cycloimidoylation of 2-Isocyano-2,3-diarylpropanoates.

A Pd-catalyzed site-selective C(sp2)-H activation/cycloimidoylation of 2-isocyano-2,3-diarylpropanoates to construct diverse cyclic imine products has been developed. Six-membered 3,4-dihydroisoquinolines containing a C3 quaternary carbon center were generated dominantly by using bulky Ad2P n-Bu as a ligand, while five-membered 1,1-disubstituted 1 H-isoindoles were formed preferentially in the presence of bidentate phosphine ligand DPPB. The selectivity for 1 H-isoindole formation was enhanced by using steric hindered aryl iodides. DFT calculations suggested that the experimentally observed ligand-controlled selectivity was a result of trans effect.

Computational Studies on Reaction Mechanism and Origins of Selectivities in Nickel-Catalyzed (2 + 2 + 2) Cycloadditions and Alkenylative Cyclizations of 1,6-Ene-Allenes and Alkenes.

The reaction mechanism and origins of ligand-controlled selectivity, regioselectivity, and stereoselectivity of Ni-catalyzed (2 + 2 + 2) cycloadditions and alkenylative cyclizations of 1,6-ene-allenes and alkenes were studied by using density functional theory. The catalytic cycle involves intermolecular oxidative coupling and an intramolecular concerted 1,4-addition step to afford a stable metallacycloheptane intermediate; these steps determine both the regioselectivity and stereoselectivity. Subsequent C-C reductive elimination leads to the cyclohexane product, whereas the β-hydride elimination leads to the trans-diene product. The selectivity between (2 + 2 + 2) cycloadditions and alkenylative cyclizations is controlled by the ligand. Irrespective of the nature of the terminal substituents on the ene-allene and alkene, the P(o-tol)3 ligand always favors the C-C reductive elimination, resulting in the cyclohexane product. On the other hand, the flexibility of the PBu3 ligand means that electronic and steric factors play important roles. Electron-withdrawing groups such as CO2Me in the ene-allene terminal substituent induce obvious substrate-ligand repulsion and destabilize the C-C reductive elimination, giving rise to the trans-diene product.

Mechanism and Origins of Ligand-Controlled Linear Versus Branched Selectivity of Iridium-Catalyzed Hydroarylation of Alkenes

The iridium-catalyzed carbonyl-directed hydroarylation of monosubstituted alkenes developed by Bower and co-workers [Crisenza, G. E. M.; McCreanor, N. G.; Bower, J. F. J. Am. Chem. Soc. 2014, 136, 10258–10261] provides an efficient strategy for highly branched-selective hydroarylation of both aryl- and alkyl-substituted alkenes. Density functional theory calculations in the present study revealed that the unique regiochemical control in this reaction is due to an unconventional modified Chalk–Harrod-type mechanism. Instead of the commonly accepted Chalk–Harrod-type mechanism of transition metal-catalyzed hydroarylation that involves C–H oxidative addition, olefin migratory insertion into the Ir–H bond, and C–C reductive elimination, the Ir-catalyzed reaction occurs via migratory insertion of the olefin into the Ir–aryl bond and C–H reductive elimination. The experimentally observed ligand-controlled selectivity is attributed to a combination of electronic and steric effects in the selectivity-determining ...

Mechanism and Selectivity in Rhodium-Catalyzed [7 + 2] Cycloaddition and Cyclopropanation/Cyclization of Allenylcyclopentane-alkynes: Metallacycle-Directed C(sp(3))-C(sp(3)) vs C(sp(3))-H Activation.

The rhodium-catalyzed [7 + 2] cycloaddition and cyclopropanation/cyclization of allenylcyclopentane-alkynes developed by Mukai and co-workers ( J. Am. Chem. Soc. 2012 , 134 , 19580 - 19583 ) represents a rare example of the metallacycle-directed selective C(sp(3))-C(sp(3)) vs C(sp(3))-H activation. In this article, the mechanism of this intriguing reaction is investigated by means of density functional theory calculations. The calculations show that the reaction is initiated by an oxidative cyclization to form the key rhodacycle intermediate. The subsequent competing β-carbon elimination/C(sp(3))-C(sp(2)) reductive elimination and metal-assisted σ-bond metathesis/C(sp(3))-C(sp(3)) reductive elimination lead to the [7 + 2] cycloaddition and cyclopropanation/cyclization, respectively. The calculations reproduce quite well the experimentally observed ligand-controlled selectivity, showing that both electronic and steric effects of the ligand have an important impact on the selectivity. In particular, the ligand can significantly affect energy barriers of the metal-assisted σ-bond metathesis and C-C reductive elimination but toward opposite directions, resulting in a selectivity switch between the [7 + 2] cycloaddition and cyclopropanation/cyclization upon ligand change.

Mechanistic Study on Ligand-Controlled Rh(I)-Catalyzed Coupling Reaction of Alkene-Benzocyclobutenone

Recently, Dong’s group [Angew. Chem., Int. Ed. 2012, 51, 7567–7571; Angew. Chem., Int. Ed. 2014, 53, 1891–1895] reported the ligand-controlled selectivity of Rh-catalyzed intramolecular coupling reaction of alkene-benzocyclobutenone: the direct coupling product (i.e., fused-rings) was formed in the DPPB-assisted system (DPPB = PPh2(CH2)4PPh2), while the decarbonylative coupling product (i.e., spirocycles) was generated in the P(C6F5)3-assited system. To explain this interesting selectivity, density functional theory (DFT) calculations have been carried out in the present study. It was found that the direct and decarbonylative couplings experience the same C(acyl)–C(sp2) activation and alkene insertion steps. The following C–C reductive elimination or β-H elimination–decarbonylation–reductive elimination leads to the direct or decarbonylative coupling reaction, respectively. The coordination features of different ligands were found to significantly influence C–C reductive elimination and decarbonylation step. The requisite phosphine dissociation of DPPB ligand from Rh center for the decarbonylation step is disfavored, and thus, the reductive elimination and direct coupling reaction are favored therein. By contrast, a free coordination site is available on the Rh center in the P(C6F5)3-assisted system, facilitating the decarbonylation process together with the generation of related decarbonylative coupling product.

Mechanisms for the synthesis of conjugated enynes from diphenylacetylene and trimethylsilylacetylene catalyzed by a nickel(0) complex: DFT study of ligand-controlled selectivity.

Density functional theory (DFT) was utilized to elucidate the reaction mechanisms of and the key factors that influence the Ni(0)-catalyzed cross-dimerization and -trimerization of trimethylsilylacetylene (R1) and diphenylacetylene (R2). Calculated results revealed that the electron-donating ability of the ligand plays a crucial role in determining the regionselectivity of this tandem reaction. The use of strongly electron-donating ligands favors the formation of cross-dimer intermediates, whereas cross-trimer products can easily be synthesized using weakly electron-donating ligands. A simple method of estimating the electron-donating abilities of different ligands based on the Mulliken charge distribution of the ligand-ligand pair was employed. The present theoretical results allow us to elucidate the reaction mechanisms for and to identify the factors that exert the greatest influence on the ligand-controlled cross-dimerization and -trimerization of trimethylsilylacetylene and diphenylacetylene. Guidelines for the design of novel ligand systems with Ni(0) catalysts are also proposed.

Density Functional Theory Study on the Mechanism of Rh-Catalyzed Decarboxylative Conjugate Addition: Diffusion- and Ligand-Controlled Selectivity toward Hydrolysis or β-Hydride Elimination

The mechanism of Rh-catalyzed decarboxylative conjugate addition has been investigated with Density Functional Theory (DFT). Calculations indicate that the selectivity toward hydrolysis or β-hydride elimination of the investigated reaction is a compromise between diffusion control and kinetic control. Ligand control can be adjusted by modifying the intermolecular interaction between the Rh(I) enolate intermediate and water.

Ligand-Controlled Selectivity in the Desymmetrization of meso Cyclopenten-1,4-diols via Rhodium(I)-Catalyzed Addition of Arylboronic Acids

A highly enantioselective desymmetrization of meso cyclopent-2-ene-1,4-diethyl dicarbonates has been developed using a Rh-catalyzed asymmetric allylic substitution. Depending on the type of ligand used, each of two regioisomeric products can be obtained in good yield and excellent enantioselectivity. Under rhodium(I) catalysis, bisphosphine P-Phos ligands form trans-1,2-arylcyclopentenols as the major product, whereas Segphos ligands lead predominantly to trans-1,4-arylcyclopentenols.

Ancillary Ligand-Controlled Selectivity for Metal or Cyclopentadienyl Ring Fluoroalkylation in Reactions of Fluoroalkyl Iodides with Cyclopentadienylrhodium Complexes

Reactions of [Rh(η5-C5H5)(CO)2] with isomeric primary and secondary fluoroalkyl iodides proceed by selective fluoroalkylation at the metal center to give [Rh(η5-C5H5)(CO)(RF)I], and treatment of these compounds with excess PMe3 affords cationic fluoroalkyl complexes [Rh(η5-C5H5)(PMe3)2(RF)]+I-. In contrast, reactions of [Rh(η5-C5H5)(PMe3)2] with the same fluoroalkyl iodides proceed with completely different selectivity to afford ring-exo-fluoroalkylated products [Rh(η4-C5H5RF)(PMe3)2I], which, in turn, react with Ag+BF4- to give the cationic hydrido complexes [Rh(η5-C5H4RF)(PMe3)2H]+[BF4]-.