Olefination Reaction Research Articles

The Atmosphere Matters: The Effect of “Inert” Gas on the Catalytic Outcomes in Cobalt-Mediated Alkyne and Olefin Hydroboration

We present a highly efficient cobalt-mediated hydroboration reaction of alkynes and alkenes enabled by a π-acidic and redox-active pyrimidinediimine (PPymDI) core. The entry point in the catalytic cycle is on a cobalt dinitrogen complex rather than cobalt hydride species, which are commonly postulated in hydroelementation reactions. Stoichiometric studies have demonstrated that both cobalt hydrides and dinitrogen complexes can be generated from the same precursors and under the same reaction conditions, with the sole difference being the reaction atmosphere (argon vs N2). Nevertheless, while the PPymDI-based cobalt dinitrogen complex is highly active (TOF = 1100 h–1 at t1/2, RT), the hydride analogue displays only modest conversions at slow reaction rates. Under the optimized conditions, a wide range of vinyl and alkyl organoboron derivatives can be obtained with high catalytic efficiency. Mechanistic studies suggest that, due to the increased π-acidity of the PPymDI core, initial formation of Co-π-complexes is preferred, followed by the oxidative addition of borane, which is the turnover-limiting step. This sequence of catalytic steps is supported by a Hammett analysis, which shows that the hydroboration reaction proceeds more rapidly for electron-rich substrates. The electronic structure of all relevant species was investigated in detail by computational, crystallographic, and spectroscopic means, revealing ligand involvement in the redox processes.

Trinuclear Gold‐Catalyzed 1,2‐Difunctionalization of Alkenes

AbstractActivated alkyl halides have been extensively explored to generate alkyl radicals with Ru‐ and Ir‐ photocatalysts for 1,2‐difunctionalization of alkenes, but unactivated alkyl bromides remain challenging substrates due to their strong reduction potential. Here we report a three‐component 1,2‐difunctionalization reaction of alkenes, unactivated alkyl bromides and nucleophiles (e.g., amines and indoles) using a trinuclear gold catalyst [Au3(tppm)2](OTf)3. It can achieve the 1,2‐aminoalkylation and 1,2‐alkylarylation readily. This protocol has a broad reaction scope and excellent functional group compatibility (>100 examples with up to 96 % yield). It also affords a robust formal [2+2+1] cyclization strategy for the concise construction of pyrrolidine skeletons under mild reaction conditions. Mechanistic studies support an inner‐sphere single electron transfer pathway for the successful cleavage of inert C−Br bonds.

Trinuclear Gold-Catalyzed 1,2-Difunctionalization of Alkenes.

Activated alkyl halides have been extensively explored to generate alkyl radicals with Ru- and Ir- photocatalysts for 1,2-difunctionalization of alkenes, but unactivated alkyl bromides remain challenging substrates due to their strong reduction potential. Here we report a three-component 1,2-difunctionalization reaction of alkenes, unactivated alkyl bromides and nucleophiles (e.g., amines and indoles) using a trinuclear gold catalyst [Au3 (tppm)2 ](OTf)3 . It can achieve the 1,2-aminoalkylation and 1,2-alkylarylation readily. This protocol has a broad reaction scope and excellent functional group compatibility (>100 examples with up to 96 % yield). It also affords a robust formal [2+2+1] cyclization strategy for the concise construction of pyrrolidine skeletons under mild reaction conditions. Mechanistic studies support an inner-sphere single electron transfer pathway for the successful cleavage of inert C-Br bonds.

Computational Investigations of Reaction Mechanisms and Transformation Products of Olefins with Hypochlorous Acid.

Hypochlorous acid (HOCl) as the main component in chlorination and also as the innate immune factor relevant to immune defense has attracted considerable attention. Electrophilic addition reaction of olefins with HOCl, one of the most important prototype of chemical reactions, has been intensively studied for a long time; however, it has not been fully understood yet. In this study, addition reaction mechanisms and transformation products of model olefins with HOCl were systematically investigated by the density functional theory method. The results indicate that the traditionally believed stepwise mechanism with a chloronium-ion intermediate is only suitable for olefins substituted with electron-donating groups (EDGs) and weak electron-withdrawing groups (EWGs) but it is a carbon-cation intermediate that is favorable for EDGs featuring p-π or π-π conjugation with the C═C moiety. Moreover, olefins substituted with moderate or/and strong EWGs prefer the concerted and nucleophilic addition mechanisms, respectively. Epoxide and truncated aldehyde as the main transformation products can be generated from chlorohydrin through a series of reactions involving hypochlorite; however, their generation is kinetically not as feasible as the formation of chlorohydrin. The reactivity of three chlorinating agents (HOCl, Cl2O, and Cl2) and the case study of chlorination and degradation of cinnamic acid were also explored. Additionally, APT charge on the double-bond moiety in olefin and energy gap (ΔE) between the highest occupied molecular orbital (HOMO) energy of olefin and the lowest unoccupied molecular orbital (LUMO) energy of HOCl were found to be good parameters to distinguish the regioselectivity of chlorohydrin and reactivity of olefin, respectively. The findings of this work are helpful in further understanding the chlorination reactions of unsaturated compounds and identifying complicated transformation products.

Cross-Coupling Reactions between Alkenes by C–H Cyclometalation

AbstractAlkenes are one of the most abundant raw feedstocks and are utilized to construct complex chemicals, whilst cross-coupling reactions using alkenes represents a powerful method toward valuable chemicals. In the past decade, cross-coupling reactions of simple alkenes by chelation-assisted alkenyl C–H functionalization has attracted significant attention due to its atom/step efficiency and excellent Z/E selectivity, proceeding by C–H exo-cyclometalation and endo-cyclometalation. In this account, we summarize transition-metal-catalyzed cross-coupling reactions between alkenes to generate 1,3-dienes via C–H alkenylation,1,4-dienes through C–H allylation, multisubstituted alkenes via hydroalkenylation, and heterocycles by way of tandem alkenyl C–H functionalization/annulation. Asymmetric alkenyl C–H alkenylation to prepare axially chiral aryl 1,3-dienes is also discussed.1 Introduction2 Alkenyl C–H Alkenylation2.1 By endo-Cyclometalation2.2 By exo-Cyclometalation3 Alkenyl C–H Allylation3.1 By endo-Cyclometalation3.2 By exo-Cyclometalation4 Alkenyl C–H Alkylation via Hydroalkenylation5 Cascade Reactions6 Conclusion

Valorisation of waste biomass and plastics toward light aromatics: Co-catalytic fast pyrolysis of torrefied bamboo and polyethylene over alkali and acid treated hierarchical HZSM-5

Light aromatics are extremely important building blocks which can be prepared from the co-catalytic fast pyrolysis (Co-CFP) of biomass and polyethylene. In this study, the bamboo was torrefied to remove part of oxygen element prior to pyrolysis, then being co-fed with polyethylene (HDPE, PE and LDPE) during CFP over alkali (NaOH and Na2CO3) and acid (H3PO4 and HCl) treated HZSM-5. 40.3% oxygen element in bamboo could be eliminated at torrefaction temperature of 300 °C. After the acid dealumination or alkali desilication treatments, the mesopore was creased in HZSM-5, transforming into hierarchical structure with larger pore size and lower acidity. The effect of torrefaction temperature, the species of alkali or acid solutions and their concentrations, the mass ratio of HDPE-to-torrefied bamboo, the CFP temperature on the yields of light aromatics was systematically discussed. The maximum yield of BTX was 4.39 × 108 a.u./mg which was obtained by Co-CFP of torrefied bamboo (250 °C) and HDPE at mass ratio of 1:2 with 800 °C over 0.2 M NaOH treated hierarchical HZSM-5. The aromatization reaction of olefins, the deoxygenation reaction of oxygenates, and the Diels-Alder reaction between furans and olefins were key reactions for the formation of BTX during Co-CFP of torrefied bamboo and polyethylene.

Visible Light-Mediated Quantum Dot Photocatalysis Enables Olefination Reactions at Room Temperature

The ability of quantum dots (QDs) to photocatalyze organic reactions is gaining attention because of their distinct light harvesting properties over traditional precious metal- and small molecule-based catalysts. However, establishing the potency of QD photocatalysts in diverse and useful organic transformations, as well as deciphering the charge transfer mechanism, is essential to cement their place as an efficient photocatalyst in synthetic chemistry. Here, we report the use of QDs in efficiently catalyzing a series of olefination reactions under visible-light irradiation at room temperature (90% yield). Spectroscopic and electrochemical studies reveal intriguing insights on the charge transfer mechanism involved in QD-photocatalyzed olefination. Interestingly, the dual role of triphenylphosphine─as a surface passivating agent and nucleophile─turned out to be decisive in directing the charge transfer process from the QD to the reactant. Benzyl triphenylphosphonium bromide salt was accepting the electrons from the photoexcited QDs, thereby initiating the catalytic olefination reaction. QD-photocatalyzed olefination was demonstrated with formaldehyde as well, resulting in the formation of industrially relevant terminal alkene, namely styrene. Moreover, the environmentally friendly indium phosphide (InP) QD also photocatalyzed the olefination reaction under mild reaction conditions, which proves the practical suitability of our study. This work presents an attractive and efficient way to introduce double bonds in organic molecules using QDs and visible light at room temperature.

Nickel‐Catalyzed Intramolecular Alkene Difunctionalization by Ball‐Milling

AbstractA mechanochemical nickel‐catalyzed intramolecular difunctionalization reaction of alkene tethered aryl halides with alkyl halides is herein described. This method allows for synthesis of 3,3‐disubstituted heterocycles, namely oxindoles, with shorter reaction times than solution‐phase counterparts. Additionally, this process is solvent minimized, with DMA used in liquid‐assisted grinding (LAG) quantities and circumvents the need for chemical activation of the terminal reductant (manganese) through mechanical grinding. The process can be scaled up to yield over a gram of product and modest enantioinduction is possible by utilizing a chiral PyrOx ligand.magnified image

Photoinduced Palladium-Catalyzed 1,2-Difunctionalization of Electron-Rich Olefins via a Reductive Radical-Polar Crossover Reaction

Palladium-catalyzed cross-coupling reactions belong to the most important transformations for the construction of C–C or C-heteroatom bonds. More recently, the photochemical activation of palladium complexes emerged as a key strategy to leverage palladium catalysis at room temperature beyond the scope of conventional cross-coupling chemistry. Herein, we report on the photoinduced palladium-catalyzed 1,2-difunctionalization reaction of electron-rich olefins. Mechanistic experiments and computational studies reveal that this reaction proceeds via the addition of an alkyl radical, followed by the oxidation of a radical intermediate to access carbocation intermediates, which are inaccessible via classic thermal reaction conditions. The carbocation can then be applied to a variety of secondary C–C or C–N bond-forming reactions. This strategy now allows a general approach toward densely functionalized unsymmetric 1,1-bis(heterocyclyl)alkanes.

Divergent Synthesis of Organofluorinated Molecules from Titanium Mediated Deoxygenation of Free Alcohols

Comprehensive SummaryAlcohols as among the most widely occurring organic compounds known, deoxygenative transformations of free alcohols as partners in radical addition reactions remain formidable challenges with great opportunities to achieve new and useful transformations. Herein, we report a protocol via C—O bond cleavage and C—C bond‐forming reaction of trifluoromethyl alkenes with free alcohols assisted by titanium reagents via a deoxygenative radical strategy, enabling the divergent synthesis for functional‐group‐rich organofluorinated compounds in high efficiencies. In this transformation, tertiary alcohols by Ti‐catalysis could be converted to trifluoromethyl alkanes without defluorination in acidic conditions, while benzyl alcohols are employed by Ti‐mediated activation to supply the gem‐difluoroalkenes with defluorination in the presence of a base. This protocol is applicable for a broad range of trifluoromethyl alkenes with good functional group tolerance and a variety of tertiary alcohols and benzyl alcohols (including primary, secondary, and tertiary alcohols), and is scalable to the gram level. Remarkably, the utility of this protocol is demonstrated by several derivatizations and late‐stage functionalization of drug molecules. The successful applications in scale up reactions and late‐stage functionalization of several drug molecules demonstrate its potential synthetic value in drug discovery settings.

Hydrogen Atom Transfer for C(sp3)−H Functionalization Enabled by Photoredox/Thianthrene/Methanol Synergistic Catalysis

AbstractA synergetic catalytic system of organophotocatalyst 4CzIPN, thianthrene, and methanol was developed for visible‐light‐induced Giese reactions of various alkanes and alkenes, upon using alkoxy radicals as hydrogen atom transfer reagents. The reaction can be performed under mild conditions to provide the alkylated products in moderate to excellent yields, avoiding the use of any strong oxidants and transition metal reagents. Different from the known LMCT and PCET processes, the key to success of this approach is the in situ thianthrenation of methanol by thianthrene radical cation to trigger the generation of methoxy radical.

Probing the effect of nitrate anion in CAN: An additional opportunity to reduce the catalyst loading for aerobic oxidations

Catalyzed by cerium ammonium nitrate (CAN), the oxidative cracking reaction of alkenes occurred to produce carbonyls in good yields under mild conditions. The reaction employed molecular oxygen (O2) as the safe and clean oxidant. The catalyst dosage was reduced to as low as 0.5 mol%, while no additive was required. Thus, it may afford a generally green synthetic approach for introducing oxygen into organic molecules as well as the biomass degradation and the resource recycling from the C=C bond-containing waste polymers. X-ray photoelectron spectroscopy (XPS) analysis and control experiments demonstrated that the process proceeded via a single electron transfer (SET) reaction-initiated free radical reaction mechanism. In the process, both Ce and NO3− acted as the oxygen carrier to promote the oxidation reaction. The application of the abundantly existed nitrate in CAN was found to be the key for reducing the catalyst loading.

Catalytic Asymmetric Cyclopropanations with Nonstabilized Carbenes.

Cyclopropanes are common building blocks in pharmaceuticals, agrochemicals, and organic materials. The most general methods for the synthesis of chiral cyclopropanes are catalytic additions of diazoalkanes to alkenes. However, a limitation of this approach is that diazoalkanes can only be safely handled on preparative scales if they possess stabilizing substituents. Here we show that gem-dichloroalkanes can serve as precursors to nonstabilized carbenes for asymmetric cyclopropanation reactions of alkenes. The process uses a cobalt catalyst and is proposed to involve the formation of a cationic carbenoid species bearing structural resemblance to the Simmons-Smith reagent. High levels of enantioselectivity are observed for monosubstituted, 1,1-disubstituted, and internal alkenes. The reaction is compatible with alkyl-substituted carbenes, which are susceptible to undergoing competing 1,2-hydride shifts.

Radical Cascade Cyclization of Alkene‐Tethered Compounds: Versatile Approach towards Ring‐Fused Polycyclic Structures

AbstractRing‐fused polycyclic structures widely exist in a myriad of natural products and pharmaceutical molecules. Consequently, the construction of such structures from readily available substrates becomes an important researching topic in organic synthesis. Triggered by the addition of radicals to the (activated or unactivated) double bonds in alkenes, the subsequent intramolecular addition/cyclization leads to polycyclic compounds. Following this procedure, a variety of functionalized ring‐fused structures were formed. Great achievements have been witnessed recently. Those works provided efficient, atom economy, and operational simple approaches toward versatile functionalized polycyclic structures from readily available alkene‐based substrates. Here, we summarized the recent achievements on the formation of ring‐fused polycyclic structures via the radical‐triggered cascade reactions of alkenes. Construction of polycyclic structures with no less than 3 fused rings developed during the last decade were included in this Review, corresponding mechanisms were also discussed.

Decarboxylative Mannich Reactions with N‐Alkyl Imines

AbstractThe use ofN‐alkyl imines in decarboxylative Mannich reaction with substituted malonic acids half oxyesters (SMAHOs) has been developed to afford a direct access to secondary β2,3‐aminoesters. The transformation occurs under very practical conditions (DABCO as a catalyst in bulk toluene and open to air) and can be performed with a broad range of each substrate in yields of 36 to 97 %. Importantly, the reaction was found to require the use of acidic additives in combination with the organocatalyst to limit the competitive olefination reaction.

Iridium/Zinc-Co-Catalyzed Ring-Opening Reactions of Oxabicyclic Alkenes with Indole Nucleophiles: A Combined Experimental and Theoretical Study

An experimental and theoretical investigation on the iridium/zinc-co-catalyzed ring-opening reactions of oxabicyclic alkenes with indole nucleophiles is reported. The reaction affords trans-3-indolyl-1,2-dihydronaphthalen-1-ol products in good yield with no N-alkylated products observed. The C–C bond-forming reaction does not require prior functionalization and is entirely atom-economic. The mechanism and origins of selectivity in the iridium-catalyzed ring-opening reaction have been examined at the M06-D3/Def2TZVPP level of theory. Orbital analysis and natural population analysis charges demonstrate that the Cα site of the π-allyliridium intermediate is the most electrophilic site of attack. Distortion/interaction analysis reveals that the chemoselectivity likely originates from an earlier-stage transition state between Cα and C3, which requires less distortion energy compared to Cα–N1 during the rate-determining intermolecular nucleophilic attack. Moreover, conceptual density functional theory was used to conceptualize the preferential reactive sites of the nucleophiles probed. The C–C bond-forming step is speculated to proceed through a Friedel–Crafts-type reaction.

Development of Electrophilic Radical Perfluoroalkylation of Electron-Deficient Olefins.

Fluorinated organic compounds have attracted significant attention over the past few decades owing to their unique properties and versatility. An established method for the synthesis of fluorinated organic compounds involves radical perfluoroalkylation reactions towards double bonds. In this radical pathway, electrophilic perfluoroalkyl radicals exhibit excellent reactivity towards electron-rich olefins. Therefore, several splendid perfluoroalkylation reactions of electron-rich olefins have been reported. However, there are only a few examples of reaction involving electron-deficient olefins because of their poor electronic compatibility with perfluoroalkyl radicals. This review focuses on the reports that challenge this long-standing issue. Radical perfluoroalkylation/bifunctionalization reactions of electron-deficient olefins are described according to the radical generation methods.

Olefination of carbonyls with alkenes enabled by electrophotocatalytic generation of distonic radical cations.

The conversion of carbonyls to olefins is a transformation of great importance for complex molecule synthesis. Standard methods use stoichiometric reagents that have poor atom economy and require strongly basic conditions, which limit their functional group compatibility. An ideal solution would be to catalytically olefinate carbonyls under nonbasic conditions using simple and widely available alkenes, yet no such broadly applicable reaction is known. Here, we demonstrate a tandem electrochemical/electrophotocatalytic reaction to olefinate aldehydes and ketones with a broad range of unactivated alkenes. This method involves the oxidation-induced denitrogenation of cyclic diazenes to form 1,3-distonic radical cations that rearrange to yield the olefin products. This olefination reaction is enabled by an electrophotocatalyst that inhibits back-electron transfer to the radical cation intermediate, thus allowing for the selective formation of olefin products. The method is compatible with a wide range of aldehydes, ketones, and alkene partners.

Role of Zn-Al oxide structure and oxygen vacancy in bifunctional catalyst for syngas conversion to light olefins

Metal oxide plays a vital role in bifunctional tandem-catalyzed CO hydrogenation to light olefins. Herein, a series of Zn-Al metal oxides were prepared and then physically mixed with SAPO-18, the prepared bifunctional catalyst was applied in direct conversion of syngas to light olefins. The effects of structure and oxygen vacancy of Zn-Al oxide were studied by changing the preparation method and the sequence of precipitation. The sequential-precipitated ZA-SP oxide exhibits the ZnAl2O4 spinel structure and no obvious crystalline phase of γ-Al2O3 or ZnO. Compared with the reverse- or co-precipitated or the impregnated Zn-Al oxides, ZA-SP oxide possesses the highest oxygen vacancy content and amounts of desorbed CO, which facilitates the CO adsorption and activation. The adsorbed and activated CO on the surface of Zn-Al oxide converted to *CH3O intermediates with the dissociated H species on −Zn−O− sites, and then formed reaction intermediates as in methanol to olefins reaction. After optimizing the calcination temperature of ZA-SP oxide, weight ratio of ZA-SP to SAPO-18, reaction temperature, and gas hourly space velocity, the ZA-SP/SAPO-18 bifunctional catalyst exhibits the highest light olefins space time yield of 10.0 mmol·gcat−1·h−1 at a CO conversion of 40.2 %, which outperforms the previous reported values.

Double Click: Unexpected 1:2 Stoichiometry in a Norbornene-Tetrazine Reaction.

We report a new reactivity for the inverse electron demand Diels-Alder (iEDDA) reaction between norbornene and tetrazine. Instead of simple 1:1 condensation between norbornene- and tetrazine-conjugated biomolecules, we observed that dimeric products were preferentially formed. As such, an olefinic intermediate formed after the addition of the first tetrazine unit to norbornene rapidly undergoes a consecutive cycloaddition reaction with a second tetrazine unit to result in a conjugate with a 1:2 stoichiometric ratio. This unexpected dimer formation was consistently observed in the reactions of both small-molecule norbornenes and tetrazines, as well as oligonucleotide conjugates. When norbornene was replaced with bicyclononyne to bypass the formation of this olefinic reaction intermediate, the reactions resulted exclusively in rapid formation of the expected 1:1 stoichiometric conjugates.