Markovnikov Selectivity Research Articles

A General Photoactive H-Bonding EDA Complex Model Drives the Selective Hydrothiolation and Hydroxysulfenylation of Carbonyl Activated Alkenes.

Excitation of photoactive electron donor-acceptor (EDA) complexes to generate radical is a promising approach in radical chemistry. In this study, we introduce a new model of H-bonding EDA complexes for the selective hydrothiolation and hydroxysulfenylation of carbonyl-activated alkenes with diverse thiols under visible light conditions. The reliability of this H-bonding EDA complex model has been confirmed by meticulous experimental and theoretical calculations. Mechanistic investigations have revealed the significant influence of the solvent in determining whether the excitation of photoactive H-bonding EDA complex leads to charge transfer (CT) or energy-charge transfer (En-CT), thereby controlling Markovnikov and anti-Markovnikov selectivity. Notably, the Quantum Theory of Atoms in Molecules (QTAIM) analysis clearly shows that the excited state of the C=O-H-S EDA complex involves closed-shell partially covalent interactions.

Nickel‐Catalyzed Branch Selective C‐H Alkylation of Indoles and Azoles with Alkenes: An Additive‐ and Solvent‐Free Approach

The development of sustainable protocols for the synthesis of alkylated heteroarenes is crucial owing to their widespread existence in medicinally relevant and bioactive natural products. Herein, we describe an efficient, additive‐ and solvent‐free approach for the regioselective C−H alkylation of indoles and azoles with alkenes using a nickel catalyst, which proceeds through a chelation‐assistance strategy. The reaction exclusively provided branched alkylated products with the compatibility of alkyl, alkoxy, fluoro, trifluoromethyl, alkene, cyano, ester, and carbonyl groups. This protocol is applicable to other heteroarenes, such as imidazoles and benzimidazoles, providing the desired alkylated products with exclusive Markovnikov selectivity. The synthetic utility and scale‐up of the reaction are demonstrated, and the protocol is in concord with the principles of green chemistry. Alkylation proceeds through facile and reversible C−H nickelation and alkene insertion processes, presumably involving rate‐limiting reductive elimination.

Markovnikov selective hydroaminocarbonylation of alkenes over a porous monophoshine polymer supported palladium catalyst

Here we develop a porous monophoshine polymer supported Pd catalyst (Pd/POL-m-3vPPh3) for hydroaminocarbonylation of aromatic alkenes with amines, showing excellent catalytic activity (up to 97% yield) and Markovnikov selectivity (up to 99%).

Wacker-type oxidation of styrenes with Markovnikov selectivity using copper as a site-selective sequential photooxidant–photoreductant

Copper acts as a site-selective photooxidant and photoreductant, thus enabling the Wacker-type oxidation of styrenes to acetophenones.

Regioselective Markovnikov hydrothiolation of 1-aryl-1,3-butadienes with dithiocarbamic acid to allyl dithiocarbamates.

A metal, ligand and solvent-free three component reaction of 1-aryl-1,3-butadienes, CS2 and amine has been developed. In this process, readily available CS2 and secondary amines were used for C-N and C-S bonds giving allyl dithiocarbamates with notable Markovnikov selectivity, mild reaction conditions, simple operation and compatibility with various functional groups (37 examples). This is first case of dithiocarbamic acid addition to an unsymmetrical 1,3-diene system.

The Mechanism of Markovnikov-Selective Epoxide Hydrogenolysis Catalyzed by Ruthenium PNN and PNP Pincer Complexes.

The homogeneous catalysis of epoxide hydrogenolysis to give alcohols has recently received significant attention. Catalyst systems have been developed for the selective formation of either the Markovnikov (branched) or anti-Markovnikov (linear) alcohol product. Thus far, the reported catalysts exhibiting Markovnikov selectivity all feature the potential for Noyori/Shvo-type bifunctional catalysis, with either a RuH/NH or FeH/OH core structure. The proposed mechanisms of epoxide ring-opening have involved cooperative C-O bond hydrogenolysis involving the metal hydride and the acidic pendant group on the ligand, in analogy to the well-documented mechanism of polar double-bond hydrogenation exhibited by catalysts of this type. In this work, we present a combined computational/experimental study of the mechanism of epoxide hydrogenolysis catalyzed by Noyori-type PNP and PNN complexes of ruthenium. We find that, at least for these ruthenium systems, the previously proposed bifunctional pathway for epoxide ring-opening is energetically inaccessible; instead, the ring-opening proceeds through opposite-side nucleophilic attack of the ruthenium hydride on the epoxide carbon, without the involvement of the ligand N-H group. For both catalyst systems, the rate law and overall barrier predicted by density functional theory (DFT) are consistent with the results from kinetic studies.

Anti-Markovnikov hydrochlorination and hydronitrooxylation of α-olefins via visible-light photocatalysis

Conventional hydrofunctionalization of α-olefins with mineral acids proceeds with Markovnikov selectivity to afford branched isomers. The direct formation of linear constitutional isomers is challenging, yet anti-Markovnikov addition would be valuable for the synthesis of commodity chemicals, such as primary alcohols, which are currently only accessible via stoichiometric redox reactions, with a full equivalent of waste of both oxidant and reductant. Strategies that utilize radical intermediates have been demonstrated, but only for activated alkenes, and the direct use of aqueous mineral acids remains elusive. Here we present anti-Markovnikov addition reactions of aqueous hydrochloric and nitric acid to unactivated alkenes. The transformation is enabled by the in situ generation of photoredox-active ion pairs, derived from acridine and the mineral acid, as a combined charge- and phase-transfer catalyst. The introduction of a hydrogen atom transfer catalyst enabled us to bypass the challenging chain propagation by hydrochloric and nitric acids that originates from the high bond dissociation energy.

CO2-Promoted and Nickel-Catalyzed Direct Hydroallylation of Terminal Alkynes with Allylic Alcohols: Access to 1,4-Dienes

CO2-promoted and Ni-catalyzed direct hydroallylation of terminal alkynes with allylic alcohols has been achieved. Various 1,4-dienes could be synthesized in good yield with excellent Markovnikov selectivity for alkyl- and aryl-substituted terminal alkynes under mild reaction conditions. A gram-scale reaction gives considerable yield. Preliminary mechanistic studies support the reaction pathway through sequential carboxylation/allylnickelation/lithium bicarbonate nickelation/transmetalation in the hydroallylation of alkynes with allylic alcohols in the presence of CO2.

Transition-metal- and solvent-free regioselective hydrosilylation of alkenes and allenes enabled by catalytic sodium tert-butoxide

An efficient and sustainable method involving alkali metal Lewis base NaOtBu as a catalyst and diphenyl silane as a silane reagent for the hydrosilylation of vinylarenes, aliphatic alkenes and allenes with high regioselectivity has been developed.

Homoleptic octahedral CoII complexes as precatalysts for regioselective hydroboration of alkenes with high turnover frequencies.

Homoleptic complexes adopting octahedral coordination modes are usually less active in catalysis due to the saturated coordination around metal centers that prevents substrate activation in a catalytic event. In this work, we demonstrated that a homoleptic octahedral cobalt complex (1) of 4'-pyridyl-2,2';6',2''-terpyridine that experienced monoprotonation at the non-coordinating pyridyl moiety upon crystallization could serve as a highly efficient precatalyst for the hydroboration of styrene derivatives with Markovnikov selectivity. The solid-state structure of this precatalyst along with relevant homoleptic CoII and FeII complexes has been characterized by X-ray crystallography. In the solid state, 1 features one-dimensional hydrogen-bonded chains that are further stacked by interchain π⋯π interactions. The newly synthesized complexes (1-3) along with several known analogues (4-6) were examined as precatalysts for the hydroboration of alkenes. The best-performing system, 1/KOtBu was found to promote Markovnikov hydroboration of substituted styrenes with high turnover frequencies (TOFs) up to ∼47 000 h-1, comparable to the most efficient polymeric catalyst [Co(pytpy)Cl2]n reported to date. Although some limitations in substrate scope as well as functional group tolerance exist, the catalyst shows good promise for several relevant hydrofunctionaliation reactions.

Computational Study Revealing the Mechanistic Origin of Distinct Performances of P(O)-H/OH Compounds in Palladium-Catalyzed Hydrophosphorylation of Terminal Alkynes: Switchable Mechanisms and Potential Side Reactions.

Pd-catalyzed hydrophosphorylation of alkynes with P(O)-H compounds provided atom-economical and oxidant-free access to alkenylphosphoryl compounds. Nevertheless, the applicable P(O)-H substrates were limited to those without a hydroxyl group except H2P(O)OH. It is also puzzling that Ph2P(O)OH could co-catalyze the reaction to improve Markovnikov selectivity. Herein, a computational study was conducted to elucidate the mechanistic origin of the phenomena described above. It was found that switchable mechanisms influenced by the acidity of substrates and co-catalysts operate in hydrophosphorylation. In addition, potential side reactions caused by the protonation of PdII-alkenyl intermediates with P(O)-OH species were revealed. The regeneration of an active Pd(0) catalyst from the resulting Pd(II) complexes is remarkably slower than the hydrophosphonylation, while the downstream reactions, if possible, would lead to phosphorus 2-pyrone. Further analysis indicated that the side reactions could be suppressed by utilizing bulky substrates or ligands or by decreasing the concentration of P(O)-OH species. The presented switchable mechanisms and side reactions shed light on the co-transformations of P(O)-H and P-OH compounds in the Pd-catalyzed hydrophosphorylation of alkynes, clarify the origin of the distinct performances of P(O)-H/OH compounds, and provide theoretical clues for expanding the applicable substrate scope of hydrophosphorylation and synthesizing cyclic alkenylphosphoryl compounds.

Decarbonylative Transfer Hydrochlorination of Alkenes and Alkynes Based on a B(C6 F5 )3 -Initiated Grob Fragmentation.

Readily available cyclohexa‐2,5‐dien‐1‐ylcarbonyl chloride derivatives are introduced as bench‐stable HCl surrogates for transfer hydrochlorination of terminal and internal alkenes as well as selected alkynes. The stepwise Grob fragmentation of those acyl chlorides into chloride, carbon monoxide, a low‐molecular‐weight arene, and a proton is promoted by B(C6F5)3. This decarbonylative transfer process enables the addition of HCl across C−C double and triple bonds with Markovnikov selectivity at room temperature.

Iridium-Catalyzed Regiodivergent and Enantioselective Hydroalkynylation of Unactivated 1,1-Disubstituted Alkenes.

Catalytic enantioselective functionalization of unactivated 1,1-disubstituted alkenes is challenging due to the difficulty to discriminate the enantiotopic faces. Enantioselective hydrofunctionalization of unactivated 1,1-disubstituted alkenes with tunable Markovnikov and anti-Markovnikov selectivity remains elusive. We report here an amide-directed, regiodivergent and enantioselective hydroalkynylation of unactivated alkenes. The regioselectivity can be readily tuned by the choice of a proper ligand. Catalytic alkynylations occurred with tunable Markovnikov and anti-Markovnikov selectivity to afford products containing acyclic tertiary or quaternary stereocenters β to an amide. Combining a sequence of alkene isomerization and regioselective hydroalkynylation, we further realized an iridium-catalyzed formal asymmetric conjugated alkynylation of β,β-disubstituted α,β-unsaturated amides. Computational studies suggest that the regioselectivity is dictated by the ligand structures.

Cobalt‐Catalyzed Intermolecular Hydroamination of Unactivated Alkenes Using NFSI as Nitrogen Source

Comprehensive SummaryCheap metal (Fe, Mn, and Co)‐catalyzed hydroamination of alkenes has been an attractive method for synthesis of amines because of biocompatibility of metal, excellent Markovnikov selectivity and chemoselectivity. However, most reports are limited to unsaturated nitrogen sources (nitric oxide, azos, azides, cyano, etc.), for which aminated products are very limited. Notably, while used widely for fluorinating reaction, N‐fluorobenzenesulfonimide (NFSI) as amine source for hydroamination has seldom been reported. Here we developed a cobalt‐catalyzed intermolecular hydroamination of unactivated alkenes using NFSI as nitrogen source under mild conditions. The reaction exhibits excellent chemo‐ and regio‐selectivity with no hydrofluorination or linear‐selectivity products. Notably, the reaction proceeded with excellent yield even though the amount of Co(salen) catalyst was reduced to 0.2 mol%. Recently, a similar work was also reported by Zhang and coworkers (ref. 19).

Synthesis of functionalized malononitriles via Fe-catalysed hydrogen atom transfers of alkenes.

Described herein is a practical and convenient approach that enabled radical-mediated conjugate addition of unreactive alkenes to electron-deficient alkenes leading to a broad range of substituted malononitriles. These reactions are believed to proceed by Fe-catalysed hydrogen atom transfer (HAT) onto the alkenes affording carbon-centered radical intermediates with Markovnikov selectivity, followed by the capture of electron-deficient alkenes. We explored this synthesis approach under mild conditions with high efficiency and broad substrate scope and the utility is highlighted by the further synthetic transformations of the obtained substituted malononitriles.

Regioselective ring-opening of epoxides towards Markovnikov alcohols: a metal-free catalytic approach using abnormal N-heterocyclic carbene.

Herein we report the first metal-free regioselective Markovnikov ring-opening of epoxides (selectivity up to 99%) using an abnormal N-heterocyclic carbene (aNHC) to yield secondary alcohols. DFT calculations and X-ray crystallography suggest that the Markovnikov selectivity originates from the high nucleophilicity and steric factors associated with the aNHC.

SOMOphilic Alkynylation of Unreactive Alkenes Enabled by Iron-Catalyzed Hydrogen Atom Transfer

We report an efficient and practical iron-catalyzed hydrogen atom transfer protocol for assembling acetylenic motifs into functional alkenes. Diversities of internal alkynes could be obtained from readily available alkenes and acetylenic sulfones with excellent Markovnikov selectivity. An iron hydride hydrogen atom transfer catalytic cycle was described to clarify the mechanism of this reaction.

Hydrosilylation of Alkenes Using a Hydrosiloxane as a Surrogate for Me2SiH2 and Catalyzed by a Nickel‐Pincer Complex

AbstractWe have developed a hydrosilylation reaction of alkenes using 1,1,3,3‐tetramethyldisiloxane (TMDS) as a surrogate for Me2SiH2 in the presence of NaOMe, catalyzed by a bench‐stable nickel‐pincer complex supported by a monoanionic O,N,P‐tridentate ligand. The reaction of styrene derivatives proceeds smoothly under mild reaction conditions to provide the hydrosilylated products in high yields with high Markovnikov selectivity. This protocol shows a wide substrate scope and is compatible with a wide range of functional groups. Secondary hydrosilanes are also suitable under the present reaction conditions and furnish the desired products in high yields.

Ligand-Regulated Palladium-Catalyzed Regiodivergent Hydroarylation of the Distal Double Bond of Allenamides with Aryl Boronic Acid.

The ligand-regulated regiodivergent hydroarylation of the distal double bond of allenamides with aryl boronic acid was achieved in the presence of palladium(II) catalysts, delivering a variety of functionalized enamide with excellent E selectivity and Markovnikov/anti-Markovnikov selectivity. Two possible coordination intermediates were proposed to be responsible for the regiodivergent hydroarylation: (1) The coordination Intermediate I, which was proposed to be formed through the coordination of MeCN, distal double bond, phenyl to palladium, led to the aryl group away from the Intermediate I, inducing excellent E selectivity and anti-Markovnikov selectivity. (2) A switch of regioselectivity to 1,2-Markovnikov hydroarylation was obtained using bidentate phosphine ligand (dppf or Xantphos). The formed coordination Intermediate II led to the N-tether away from the Intermediate II and at the trans position of aryl, resulting in excellent E selectivity and Markovnikov selectivity. Meanwhile, tentative investigation on the mechanism proved that the hydron source of this hydroarylation is more likely to be boronic acid. The transmetallation between aryl boronic acid and palladium catalyst was the initial step of this transformation.

Cyclic (Alkyl)(amino)carbene Lanthanide Amides: Synthesis, Structure, and Catalytic Selective Hydrosilylation of Alkenes.

The first examples of cyclic (alkyl)(amino)carbene (CAAC) lanthanide (Ln) complexes were synthesized from the reaction of CAAC with Yb[N(SiMe3)2]2 and Eu[N(SiMe3)2]2(THF)2 (THF = tetrahydrofuran). The structures of (CAAC)Yb[N(SiMe3)2]2 (2) and (CAAC)Eu[N(SiMe3)2]2(THF) (3) were determined by X-ray diffraction analysis. Density functional theory calculations of 2 revealed the predominantly ionic bond between the Ln ion and CAAC. Complex 3 enabled catalytic hydrosilylation of aryl- and silylalkenes with primary and secondary silanes in high yields and Markovnikov selectivity.