Cobalt-Catalyzed Intramolecular Markovnikov Hydrocarbonylation of Unactivated Alkenes via Hydrogen Atom Transfer.

A cobalt-catalyzed intramolecular Markovnikov hydroalkoxycarbonylation and hydroaminocarbonylation of unactivated alkenes has been developed, enabling highly chemo- and regioselective synthesis of α-alkylated γ-lactones and α-alkylated γ-lactams in good yields. The mild reaction conditions allow use of mono-, di- and trisubstituted alkenes bearing a variety of functional groups. Preliminary mechanistic studies suggest the reaction proceeds through a CO-mediated hydrogen atom transfer (HAT) and radical-polar crossover (RPC) process, in which a cationic acylcobalt(IV) complex is proposed as the key intermediate.

Copper-Catalyzed Carbonylative Coupling of Alkyl Halides.

Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to introduce oxygen functionality into organic compounds, with CO acting as an inexpensive and readily available C1 feedstock. Despite the long history of carbonylation catalysis, including many processes that have been industrialized at bulk scale, there remain several challenges to tackle. For example, noble metals such as Pd, Rh, and Ir are typically used as catalysts for carbonylation reactions, rather than earth-abundant alternatives. Additionally, while carbonylation of C(sp2)-hybridized substrates (e.g., aryl halides) is well-known, carbonylation of unactivated alkyl electrophiles, especially where ß-hydride elimination can compete with desired CO migratory insertion at the catalyst site, remains challenging for many systems. Recently, base metal catalysis based on Mn, Co, and other metals has enabled advances in carbonylative coupling of alkyl electrophiles, though the nucleophiles are often limited to alcohols or amines to generate esters or amides as products. Thus, we have targeted base metal-catalyzed carbonylative C-C and C-E (E = N, H, Si, B) coupling reactions as a method for approaching diverse carbonyl compounds of synthetic importance.Initially, we designed a heterobimetallic catalyst platform for carbonylative C-C coupling of alkyl halides with arylboronic esters (i.e., carbonylative Suzuki-Miyaura coupling) to generate aryl alkyl ketones. Subsequently, we developed multicomponent carbonylation reactions of alkyl halides using NHC-Cu catalysts (NHC = N-heterocyclic carbene). These reactions operate by radical mechanisms, converting alkyl halides into either acyl radical or acyl halide intermediates that undergo subsequent C-C or C-E coupling at the Cu site. This mechanistic paradigm is relatively novel in the metal-catalyzed carbonylation area, allowing us to discover a previously unexplored chemical space in carbonylative coupling catalysis. We have successfully developed the following reactions: (a) hydrocarbonylative coupling of alkynes with alkyl halides; (b) borocarbonylative coupling of alkynes with alkyl halides; (c) reductive aminocarbonylation of alkyl halides with nitroarenes; (d) reductive carbonylation of alkyl halides; (e) carbonylative silylation of alkyl halides; (f) carbonylative borylation of alkyl halides. These reactions provide a broad range of valuable products including ketones, allylic alcohols, ß-borylenones, amides, alcohols, acylsilanes, and acylborons in an efficient manner. Notably, the preparation of some of these products has previously required multistep syntheses, harsh conditions, or specialized reagents. By contrast, the multicomponent coupling platform that we have developed requires only readily available building blocks and rapidly increases molecular complexity in a single synthetic manipulation.

C-C and C-X coupling reactions of unactivated alkyl electrophiles using copper catalysis.

Transition metal-catalysed cross-coupling reactions are widely used for construction of carbon-carbon and carbon-heteroatom bonds. However, compared to aryl or alkenyl electrophiles, the cross-coupling of unactivated alkyl electrophiles containing ß hydrogens remains a challenge. Over the past few years, the use of suitable ligands such as bulky phosphines or N-heterocyclic carbenes (NHCs) has enabled reactions of unactivated alkyl electrophiles not only limited to the traditional cross-coupling with Grignard reagents, but also including a diverse range of organic transformations via either SN2 or radical pathways. This review provides a comprehensive overview of the recent development in copper-catalysed C-C, C-N, C-B, C-Si and C-F bond-forming reactions using unactivated alkyl electrophiles.

One-Step Synthesis of Acylboron Compounds via Copper-Catalyzed Carbonylative Borylation of Alkyl Halides*.

A copper-catalyzed carbonylative borylation of unactivated alkyl halides has been developed, enabling efficient synthesis of aliphatic potassium acyltrifluoroborates (KATs) in high yields by treating the in situ formed tetracoordinated acylboron intermediates with aqueous KHF2 . A variety of functional groups are tolerated under the mild reaction conditions, and primary, secondary, and tertiary alkyl halides are all applicable. In addition, this method also provides facile access to N-methyliminodiacetyl (MIDA) acylboronates as well as α-methylated potassium acyltrifluoroborates in a one-pot manner. Mechanistic studies indicate a radical atom transfer carbonylation (ATC) mechanism to form acyl halide intermediates that are subsequently borylated by (NHC)CuBpin.

Cu-Catalyzed Carbonylative Silylation of Alkyl Halides: Efficient Access to Acylsilanes.

A Cu-catalyzed carbonylative silylation of unactivated alkyl halides has been developed, enabling efficient synthesis of alkyl-substituted acylsilanes in high yield. A variety of functional groups are tolerated under the mild reaction conditions, and primary, secondary, and tertiary alkyl halides are all applicable. The practical utility of this method has been demonstrated in the synthesis of acylsilanes bearing different silyl groups as well as in situ reduction of a product to the corresponding α-hydroxylsilane in one pot. Mechanistic experiments indicate that a silylcopper intermediate activates alkyl halides by single electron transfer to form alkyl radical intermediates and that carbon-halogen bond cleavage is not involved in the rate-determining step.

Heterobimetallic Control of Regioselectivity in Alkyne Hydrostannylation: Divergent Syntheses of α- and ( E) -ß -Vinylstannanes via Cooperative Sn-H Bond Activation.

Cooperative Sn-H bond activation of hydrostannanes (Bu3SnH) by tunable heterobimetallic (NHC)Cu-[MCO] catalysts ([MCO] = FeCp(CO)2 or Mn(CO)5) enables the catalytic hydrostannylation of terminal alkynes under mild conditions, with Markovnikov/anti-Markovnikov selectivity controlled by the Cu/M pairing. By using the MeIMesCu-FeCp(CO)2 catalyst, a variety of α-vinylstannanes were produced from simple alkyl-substituted alkynes and Bu3SnH in high yield and good regioselectivity; these products are challenging to access under mononuclear metal-catalyzed hydrostannylation conditions. In addition, reversed regioselectivity was observed for aryl-substituted alkynes under the Cu/Fe-catalyzed conditions, affording the ( E)-ß -vinylstannanes as major products. On the other hand, by using the IMesCu-Mn(CO)5 catalyst, a variety of ( E)- ß-vinylstannanes were produced from primary, secondary, and tertiary alkyl-substituted alkynes, thus demonstrating divergent regioselectivity for alkyne hydrostannylation controlled by Cu/Fe vs Cu/Mn pairing. Both methods are amenable to gram-scale vinylstannane synthesis as well as late-stage hydrostannylation in a natural-product setting. Mechanistic experiments indicate the syn addition of Bu3SnH to the alkynes and imply the involvement of Sn-H bond activation in the rate-determining step. Two distinct catalytic cycles were proposed for the Cu/Fe and Cu/Mn catalysis based on stoichiometric reactivity experiments.

Synthesis of Allylic Alcohols via Cu-Catalyzed Hydrocarbonylative Coupling of Alkynes with Alkyl Halides.

We have developed a modular procedure to synthesize allylic alcohols from tertiary, secondary, and primary alkyl halides and alkynes via a Cu-catalyzed hydrocarbonylative coupling and 1,2-reduction tandem sequence. The use of tertiary alkyl halides as electrophiles was found to enable the synthesis of various allylic alcohols bearing α-quaternary carbon centers in good yield with high 1,2-reduction selectivity. Mechanistic studies that suggested a different pathway was operative with tertiary alkyl halides compared with primary and secondary alkyl halides for generating the key copper(III) oxidative adduct. For tertiary electrophiles, an acyl halide likely forms via radical atom transfer carbonylation. The preference for 1,2-reduction over 1,4-reduction of α,ß-unsaturated ketones bearing tertiary substituents was rationalized using density functional theory transition state analysis. On the basis of this computational model, the coupling method was extended to primary and secondary alkyl iodide electrophiles by using internal alkynes with aryl substituents, providing trisubstituted allylic alcohols in high yield with good regioselectivity.

Structural characteristic and ammonium and manganese catalytic activity of two types of filter media in groundwater treatment.

Two types of filter media in groundwater treatment were conducted for a comparative study of surface structure and catalytic performance. Natural filter media was adopted from a conventional aeration-filtration groundwater treatment plant, and active filter media as a novel and promising filter media was also adopted. The physicochemical properties of these two kinds of filter media were characterized using numerous analytical techniques, such as X-Ray diffraction (XRD), scanning electron microscope (SEM), energy dispersive X-ray (EDX), X-ray photoelectron spectroscopy (XPS) and Zeta potential. The catalytic activities of these filter media were evaluated for ammonium and manganese oxidation. XRD data showed that both active filter media and natural filter media belonged to birnessite family. A new manganese dioxide (MnO2) phase (PDF#72-1982) was found in the structure of natural filter media. The SEM micrograph of natural filter media showed honeycomb structures and the active filter media presented plate structures and consisted of stacked particle. These natural filter media presented lower level of some trace elements such as calcium and magnesium, lower degree of crystallinity, lower Mn(III) content and lattice oxygen content than that of active filter media, which were associated with its poor ammonium and manganese catalytic activities. In addition, some γ-Fe2O3 and MnCO3 were found in the coating which may hinder the ammonium and manganese catalytic oxidation. This study provides a thorough and comprehensive understanding about the most commonly used filter media in water treatment, which can provide a theoretical guide to practical applications.

Copper-Catalyzed Borocarbonylative Coupling of Internal Alkynes with Unactivated Alkyl Halides: Modular Synthesis of Tetrasubstituted ß-Borylenones.

Reported is a general procedure to synthesize tetrasubstituted enones, which are borylated in the ß-position, using a copper-catalyzed four-component coupling reaction of simple chemical feedstocks: internal alkynes, alkyl halides, bis(pinacolato)diboron (B2 pin2 ), and CO. A broad scope of highly functionalized ß-borylated enones, a largely unknown class of organic compounds, can be accessed efficiently using this method. The synthesis of all-carbon tetrasubstituted enones was realized by employing the ß-borylated enone unit, without purification, in a Suzuki-Miyaura coupling. The utility of the method was further demonstrated by various transformations, including halogenation, oxidation, and protodeboration, of the corresponding reduced oxaborole species to provide densely substituted allylic alcohol and ketone products.

Cu-Catalyzed Hydrocarbonylative C-C Coupling of Terminal Alkynes with Alkyl Iodides.

A Cu-catalyzed hydrocarbonylative C-C coupling of terminal alkynes with unactivated alkyl iodides has been developed, enabling highly chemo- and regioselective synthesis of unsymmetrical dialkyl ketones. A variety of functional groups are tolerated, and both primary and secondary alkyl iodides react well. An autotandem sequence of two Cu-catalyzed processes is proposed: first hydrocarbonylative coupling of the alkyne and the alkyl iodide, followed by reduction of the intermediate unsaturated ketone to the saturated product. Mechanistic experiments indicate that an alkenylcopper intermediate activates the alkyl iodide by single electron transfer to enable a radical carbonylation pathway.

Catalytic Nucleophilic Fluorination of Secondary and Tertiary Propargylic Electrophiles with a Copper-N-Heterocyclic Carbene Complex.

A catalytic method for the nucleophilic fluorination of propargylic electrophiles is described. Our protocol involves the use of a Cu(NHC) complex as the catalyst and is suitable for the preparation of secondary and tertiary propargylic fluorides without the formation of isomeric fluoroallenes. Preliminary mechanistic investigations suggest that fluorination proceeds via copper acetylides and that cationic species are involved.

Copper-Catalyzed Protoarylation of gem-Difluoroallenes.

A copper-catalyzed protoarylation of gem-difluoroallenes with aryl boronic esters has been developed, enabling highly regioselective synthesis of gem-difluoroalkenes in high yields. The mild reaction conditions allow for a variety of functional groups to be tolerated, and the reaction can be extended to protoalkenylation of gem-difluoroallenes. The synthetic utility of this method has been demonstrated in gram-scale operation as well as synthesis of chiral gem-difluoroalkenes bearing γ-carbon stereogenic centers in moderate enantioselectivity using a chiral bidentate phosphine ligand with a copper catalyst.

Fermentation broth of food waste: A sustainable electron donor for perchlorate biodegradation.

Microbial reduction has been considered an effective way to remove perchlorate (ClO4-), during which, additional electron donors and carbon sources are required. This work aims to study the potential of fermentation broth of food waste (FBFW) serving as an electron donor for ClO4- biodegradation, and further investigates the variance of the microbial community. The results showed that FBFW without anaerobic inoculum at 96 h (F-96) exhibited the highest ClO4- removal rate of 127.09 mg/L/d, attributed to higher acetate and lower ammonium contents in the F-96 system. In a 5 L continuous stirred-tank reactor (CSTR), with a 217.39 g/m3·d ClO4- loading rate, 100% removal efficiency of ClO4- was achieved, indicating that the application of FBFW in the CSTR showed satisfactory performance for ClO4- degradation. Moreover, the microbial community analysis revealed that Proteobacteria and Dechloromonas contributed positively to ClO4- degradation. Therefore, this study provided a novel approach for the recovery and utilization of food waste, by employing it as a cost-effective electron donor for ClO4- biodegradation.

[Effects of Different Coagulants on Co-manganese Oxides Filter Media for Removing Ammonium and Manganese from Surface Water in Summer and Autumn].

Under high temperatures in summer and autumn, the effects of FeCl3, PFC, and PAFC on co-manganese oxides filter media for removing ammonium and manganese from surface water were investigated. The results showed that FeCl3 can be hydrolyzed easily, thus reducing the pH of the water and the residual iron in the water were not conducive to the removal of ammonium and manganese. Transforming the coagulant FeCl3 into PFC can effectively recover the removal effect of ammonium and manganese. After being pre-treated by PAFC, removal of ammonium and manganese during the filtering operation remained stable and excellent. Simultaneously, the structural characteristics of the filter material were analyzed. Different coagulants caused different changes of shape of filter media. As FeCl3 is a coagulant, the slow increase in specific surface area is not beneficial to removal of ammonium and manganese. Additionally, the results of FTIR spectra indicated that coagulants have different influences on the group of Fe-OH bonds of filter media. This study provides a theoretical basis for the study of the effects of water quality factors on the removal of ammonium and manganese from surface water.

Study on the Factors Affecting the Start-Up of Iron-Manganese Co-Oxide Filters for Ammonium and Manganese Removal from Groundwater.

The high concentration of ammonium (NH4⁺-N) and manganese (Mn2+) in underground water poses a major problem for drinking water treatment plants. Effective catalytic oxidative removal of NH4⁺-N and Mn2+ by iron-manganese co-oxide film (MeOx) filters was first developed by our group in a previous study. In this study, several identical pilot-scale filters were employed to optimize the start-up process for simultaneous removal of NH4⁺-N and Mn2+ from potable water supplies. Experiments were conducted to assess the influence of Mn2+ concentration, Fe2+ concentration, filtration rate and dosing time on the start-up period of the filter. Results demonstrated that the ability of the filter to remove completely 1.5 mg/L NH4⁺-N could be achieved on the sixth day at the soonest and the removal of Mn2+ could reach 1 mg/L by the 18th day. Filter R3 feeding with 1 mg/L Fe2+, 2 mg/L Mn2+ and 3.5 mg/L MnO4- during the start-up period exhibited the optimum NH4⁺-N and Mn2+ removal effect. Short dosing time was not conducive to attaining full NH4⁺-N removal in filters, especially the activity of NO2--N conversion to NO3--N. The compositional analysis and element distribution analysis results demonstrated that there was an abundance of C, O, Mn, Mg, Fe, Ca and Si across the entire area of the surface of the filter media and the elemental distribution was homogeneous, which was different from the biofilter media. Knowledge-guided performance optimization of the active iron-manganese co-oxide could pave the way for its future technological use.

Cu/Mn bimetallic catalysis enables carbonylative Suzuki-Miyaura coupling with unactivated alkyl electrophiles.

A bimetallic system consisting of Cu-carbene and Mn-carbonyl co-catalysts was employed for carbonylative C-C coupling of arylboronic esters with alkyl halides, allowing for the convergent synthesis of ketones. The system operates under mild conditions and exhibits complementary reactivity to Pd catalysis. The method is compatible with a wide range of arylboronic ester nucleophiles and proceeds smoothly for both primary and secondary alkyl iodide electrophiles. Preliminary mechanistic experiments corroborate a hypothetical catalytic mechanism consisting of co-dependent cycles wherein the Cu-carbene co-catalyst engages in transmetallation to generate an organocopper nucleophile, while the Mn-carbonyl co-catalyst activates the alkyl halide electrophile by single-electron transfer and then undergoes reversible carbonylation to generate an acylmanganese electrophile. The two cycles then intersect with a heterobimetallic, product-releasing C-C coupling step.

Enantioselective propargylic [1,3]-rearrangements: copper-catalyzed O-to-N migrations toward C-N bond formation.

We have identified an enantioselective copper-catalyzed O-to-N formal [1,3]-rearrangement to form N-propargylic-2-pyridones. This enantioconvergent O-to-N propargylic rearrangement occurs rapidly at ambient temperature and high enantioselectivity is observed for a range of 3-alkyl-substituted substrates. Stereochemical features include a mild kinetic enantioenrichment of the substrate and a non-linear relationship between product and ligand enantiopurity. Based on kinetic analyses and cross-over experiments, we put forward a mechanistic proposal involving Cu-acetylides as well as bimetallic intermediates in which coordination to the pyridyl nitrogen is likely a crucial binding interaction.

Divergent enantioselective synthesis of hapalindole-type alkaloids using catalytic asymmetric hydrogenation of a ketone to construct the chiral core structure.

A divergent enantioselective approach to hapalindole-type alkaloids is described. The route features a ruthenium-catalyzed asymmetric hydrogenation of a ketone via DKR to construct the chiral trans-1-indolyl-2-isopropenylcyclohexane skeleton and a switchable sequence of methylation and acetylation/aldol reaction to access a chiral quaternary stereocenter. (+)-Hapalindole Q (1, 13 steps, 5.9% overall yield), (-)-12-epi-hapalindole Q isonitrile (2, 15 steps, 5.5% overall yield), (-)-hapalindole D (3, 14 steps, 2.3% overall yield), and (+)-12-epi-fischerindole U isothiocyanate (4, 14 steps, 3.0% overall yield) were synthesized in 13-15 steps from a commercially available material to demonstrate the application of this approach.

Enantioselective total synthesis of (-)-Δ8-THC and (-)-Δ9-THC via catalytic asymmetric hydrogenation and S(N)Ar cyclization.

The highly efficient asymmetric total syntheses of (-)-Δ(8)-tetrahydrocannabinol ((-)-Δ(8)-THC) (13 steps, 35%) and (-)-Δ(9)-tetrahydrocannabinol ((-)-Δ(9)-THC) (14 steps, 30%) have been developed by using ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryl cyclic ketones via dynamic kinetic resolution and intramolecular S(N)Ar cyclization.