Ene Reaction Research Articles

Dearomative Carbonylations of Arenes via Bifunctional Coordination to Cr(CO)3

AbstractCarbonylation reactions serve as powerful tools to construct useful carbonyl compounds with high efficiency and atom economy. Compared with the well-developed carbonylation chemistry for alkenes, the dearomative carbonylation of arenes is largely underexplored, possibly owing to the severe challenge in overcoming resonance stabilization of arene π-systems. Bifunctional coordination to tricarbonylchromium not only offers a reliable strategy to activate inert benzene π-bonds towards dearomatizations but also provides the CO source for the carbonylation process. Herein, we highlight the recent progress in dearomative carbonylations of chromium-bound arenes through either the conventional nucleophile-electrophile addition mode or the newly-developed umpolung-enabled nucleophile-nucleophile addition mode under mild CO-gas-free conditions. Given the great abundance and diversity of arene substrates, we hope this review will attract more attention to this new direction of carbonylation chemistry.1 Introduction2 Dearomative Carbonylations of Arenes via Nucleophile-Electrophile Addition3 Dearomative Carbonylations of Arenes via Nucleophile-Nucleophile Addition4 Conclusion

Manganese- and Iron-Catalyzed Carbonylation Reactions: A Personal Account

AbstractTransition-metal-catalyzed carbonylative transformations have been widely employed to convert CO gas into valuable carbonyl-containing molecules, mainly using noble metals (Pd, Rh, Ir, Ru) and more recently nickel and other catalysts. Although noble-metal catalysts have the advantage of reaction efficiency, their high-cost has led scientists to explore alternative procedures. Also under these backgrounds, we carried out some studies on nonexpensive metal-catalyzed carbonylative transformations. In this Account, we summarize the carbonylation reactions developed in our research group by using manganese and iron catalysis. These carbonylation reactions proceeded either via SET (single-electron transfer) or TET (two-electron transfer) mechanism.1 Introduction2 Manganese-Catalyzed Carbonylation of Alkyl Chlorides3 Manganese-Catalyzed Carbonylation of Alkyl Iodides4 Iron/Copper-Catalyzed Carbonylation of Alkyl Bromides5 Iron-Catalyzed Carbonylation of Alkyl Bromides6 Iron-Catalyzed Carbonylation of Alkyl-Boronic Pinacol7 Iron-Catalyzed Aminoalkylative Carbonylative Cyclization of Alkenes8 Conclusion and Outlook

Low-Valent Tungsten Catalyzed Carbonylative Synthesis of Benzoates from Aryl Iodides and Alcohols

Non-noble metals catalyzed carbonylative reactions serve as straightforward and sustainable methods for the synthesis of functionalized carbonyl-containing compounds. Herein, a low-valent-tungsten-catalyzed reaction that enables the coupling of aryl iodides and alcohols or phenols was disclosed, employing the readily available W(CO)6 as the effective catalyst and PPh3 as ligand. Under the optimal reaction conditions, aryl iodides smoothly underwent carbonylative coupling reactions with alcohols or phenols, processing the feature of broad substrate scope and good functional groups tolerance. Furthermore, this conversion can be carried out on a gram scale, showcasing significant promise in the synthesis of pharmaceutical or biologically active compounds.

Shape‐Selective Zeolites for Tandem CO2 Hydrogenation‐Carbonylation Reactions

The valorization of carbon dioxide as a C1 building block in C‐C bond forming reactions is a critical link on the road to carbon‐circular chemistry. Activation of this inert molecule through reduction with H2 to carbon monoxide in the reverse water‐gas shift (RWGS) reaction can be followed by a wide spectrum of consecutive carbonylation reactions, but the RWGS is severely equilibrium limited at the moderate temperatures of carbonylations. Here we successfully reconcile both reactions in one pot, while avoiding incompatibilities through a zeolite‐based compartmentalized approach. More specifically, Pt encapsulated in a small‐pore LTA zeolite selectively generates carbon monoxide in mild reaction conditions; an ensuing one‐pot carbonylation reaction allows to shift the equilibrium through continuous consumption of CO. Moreover, the zeolite encapsulation avoids undesired reactions like hydrogenation of the olefin reactant through a molecular sieving effect. This strategy was first studied in‐depth for Rh‐catalyzed olefin hydroformylation with CO2/H2, affording aldehydes in good yields with high regioselectivities. The methodology was then extended to a variety of carbonylations using CO2 for the synthesis of bulk and fine chemicals.

Shape-Selective Zeolites for Tandem CO2 Hydrogenation-Carbonylation Reactions.

The valorization of carbon dioxide as a C1 building block in C-C bond forming reactions is a critical link on the road to carbon-circular chemistry. Activation of this inert molecule through reduction with H2 to carbon monoxide in the reverse water-gas shift (RWGS) reaction can be followed by a wide spectrum of consecutive carbonylation reactions, but the RWGS is severely equilibrium limited at the moderate temperatures of carbonylations. Here we successfully reconcile both reactions in one pot, while avoiding incompatibilities through a zeolite-based compartmentalized approach. More specifically, Pt encapsulated in a small-pore LTA zeolite selectively generates carbon monoxide in mild reaction conditions; an ensuing one-pot carbonylation reaction allows to shift the equilibrium through continuous consumption of CO. Moreover, the zeolite encapsulation avoids undesired reactions like hydrogenation of the olefin reactant through a molecular sieving effect. This strategy was first studied in-depth for Rh-catalyzed olefin hydroformylation with CO2/H2, affording aldehydes in good yields with high regioselectivities. The methodology was then extended to a variety of carbonylations using CO2 for the synthesis of bulk and fine chemicals.

Cascade Reactions of Alkynyl Ketones and Amides to Generate Unsaturated Oxacycles and Aromatic Carbocycles.

We describe novel amine-mediated transformation of alkynyl ketones and amides to generate 2-methylene-2H-pyrans, substituted 3-hydroxy-9H-fluoren-9-ones, and amine-incorporated arenes. These cascade processes are initiated by conjugate addition of secondary amine followed by hydrolysis of the enamine/vinylogous amide intermediates. The product distribution is highly sensitive to the steric and electronic effects of the substituents on both the alkyne moieties, the tether structure connecting them, and the nature of the amine. Alkynyl amide participates in the Alder-ene reaction favorably to generate more reactive allene amide that reacts with amine to generate amine-incorporated arene products. These metal-free cascade reactions are a useful synthetic method that can be exploited for the construction of various hetero- and carbocyclic systems.

Carbonylation Reactions at Carbon-Centered Radicals with an Adjacent Heteroatom.

Heteroatoms are essential to living organisms and present in almost all molecules with medicinal usage. The catalytic functionalization at the carbon-centered radical with an adjacent heteroatom provides an effective way to value added moiety while retaining the unique physicochemical and pharmacological properties of heteroatoms, which can promote the development of pharmaceutical and fine chemical production. Carbonylative transformation was discovered nearly a century ago which is an efficient method for the synthesis of carbonyl-containing molecules with potent applications in both industry and academia. Despite numerous advances in new reaction development, carbonylative transformation involving adjacent heteroatom carbon radical remain a subject that deserves to be discussed. In this minireview, we systematically summarized and discussed the recent advances in carbonylative transformations involving carbon-centered radicals with an adjacent heteroatom, including oxygen (O), nitrogen (N), phosphorus (P), silicon (Si), sulfur (S), boron (B), fluorine (F), and chlorine (Cl). The related reaction mechanism was also discussed.

Carbonylation Reactions at Carbon‐Centered Radicals with an Adjacent Heteroatom

AbstractHeteroatoms are essential to living organisms and present in almost all molecules with medicinal usage. The catalytic functionalization at the carbon‐centered radical with an adjacent heteroatom provides an effective way to value added moiety while retaining the unique physicochemical and pharmacological properties of heteroatoms, which can promote the development of pharmaceutical and fine chemical production. Carbonylative transformation was discovered nearly a century ago which is an efficient method for the synthesis of carbonyl‐containing molecules with potent applications in both industry and academia. Despite numerous advances in new reaction development, carbonylative transformation involving adjacent heteroatom carbon radical remain a subject that deserves to be discussed. In this minireview, we systematically summarized and discussed the recent advances in carbonylative transformations involving carbon‐centered radicals with an adjacent heteroatom, including oxygen (O), nitrogen (N), phosphorus (P), silicon (Si), sulfur (S), boron (B), fluorine (F), and chlorine (Cl). The related reaction mechanism was also discussed.

Ligand-Free Iron-Catalyzed Carbonylation of Aryl Iodides with Alkenyl Boronic Acids: Access to α,β-Unsaturated Ketones.

The application of earth-abundant and low-toxicity iron catalysts as replacements for palladium in carbonylative coupling reactions remains challenging and largely unexplored. Reported here is a highly efficient iron-catalyzed carbonylation of aryl iodides with alkenyl boronic acids under ligand-free conditions, enabling the synthesis of α,β-unsaturated ketones even at atmospheric CO pressure. The broad applicability, including its effectiveness with α-branched enones and biologically active molecules, along with high yields and selectivity, underlines the general applicability of this catalytic system.

Formate Salt as a Bifunctional Reagent for Hydroxylation and Carbonylation Reactions Under Photochemically Driven Nickel Catalysis.

In this study, we disclose for the first time that formate salt can be used as a bifunctional reagent for the synthesis of phenol derivatives and as a CO source for carbonylative cross-coupling processes using the COware gas reactor under activation free conditions. Key to this success is the in-situ synthesis of aryl formate via an unprecedented nickel/organophotocatalyst system under blue LED irradiation. This developed system demonstrated high applicability to various aryl iodide substrates for synthesizing phenol derivatives. Moreover, the generated CO could be utilized in a range of carbonylative C-heteroatom and C-C processes. Notably, commercially available H13COONa salt can serve as a bifunctional reagent for both synthesizing phenols and generating 13CO.

Palladium‐Catalyzed Four‐Component Carbonylation Reactions of Acetylene: Synthesis of β‐Perfluoroalkyl Acrylamides

AbstractThe simplest alkyne, acetylene, is a suitable C2 linker synthon that enables the connection of organic molecules with different functional groups. However, reactions of acetylene with advanced organic building blocks are much less explored compared to substituted alkynes. In this article, we present a straightforward palladium‐catalyzed four‐component carbonylation reaction with acetylene, CO, amines, and perfluoroalkyl halides that enables the preparation of various β‐perfluoroalkyl acrylamides in one step. This protocol also provides a new strategy for the late‐stage modification of bioactive molecules, as demonstrated by the construction of β‐perfluoroalkyl ibrutinib derivatives.

Carbonylative Cyclization of 2-Iodofluorobenzenes and 2-Aminophenols with Recyclable Palladium-Complexed Dendrimers on SBA-15: One-Pot Synthesis of Dibenzoxazepinones.

A novel, efficient, and practical route to dibenzoxazepinones has been developed through a one-pot heterogeneous palladium-catalyzed aminocarbonylation/aromatic nucleophilic substitution (SNAr) sequence starting from readily available 2-iodofluorobenzenes and 2-aminophenols. The carbonylative cyclization reaction proceeds smoothly in dimethyl sulfoxide (DMSO) at 120 °C with 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as the base by using a polyamidoamine (PAMAM)-dendronized SBA-15-supported bidentate phosphine-palladium complex [G(1)-2P-Pd(OAc)2-SBA-15] as the catalyst under 10 bar of CO, yielding a wide variety of dibenzo[b,e][1,4]oxazepin-11(5H)-one derivatives in good to excellent yields. Moreover, this new heterogenized dendritic palladium catalyst has competitive advantages in that it can be facilely recovered by simple filtration in air and recycled more than eight times without any significant loss of activity. The broad substrate scope, high functional group tolerance, and excellent palladium catalyst recyclability of the reaction make this approach a general, efficient, and economical method for the construction of valuable dibenzoxazepinone derivatives.

Li-Jie Cheng.

"My favorite thing about my lab group is when they discover some interesting results on their own… My favorite molecule is CO as this is an important C1 source in carbonylation reactions…" Find out more about Li-Jie Cheng in his Introducing… Profile.

Aryne Chemistry: Generation Methods and Reactions Incorporating Multiple Arynes.

Arynes hold significance for the efficient fusion of (hetero) arenes with diverse substrates, advancing the construction of complex molecular frameworks. Employing multiple equivalents of arynes is particularly effective in the rapid formation of polycyclic cores found in optoelectronic materials and bioactive compounds. However, the inherent reactivity of arynes often leads to side reactions, yielding unanticipated products and underlining the importance of a detailed investigation into the use of multiple arynes to fine-tune their reactivity. This review centers on methodologies and syntheses in organic reactions involving multiple arynes, categorizing based on mechanisms like cycloadditions, σ-bond insertions, nucleophilic additions, and ene reactions, and discusses aryne polymerization. The categorization based on these mechanisms includes two primary approaches: the first entails multiple aryne engagement within a single step while the second approach involves using a single equivalent of aryne sequentially across multiple steps, with both requiring strict reactivity control to ensure precise aryne participation in each respective step. Additionally, the review provides an in-depth analysis of the selection of aryne precursors, organized chronologically and by activation strategy, offering a comprehensive background that supports the main theme of multiple aryne utilization. The expectation remains that this comprehensive review will be invaluable in designing advanced syntheses engaging multiple arynes.

Three-component carbonylative Michael addition of aryl bromides using abundant metal-carbonyl under light

Carbonyl compounds are widely found in various chemical reactions and natural products. Herein, a light-driven carbonylative cross-coupling reaction of bromobenzene was reported. Co2(CO)8 was used as an abundant solid carbonyl source to synthesize various Michael addition products with high yields. This reaction has broad substrates scope with good functional group tolerance. The mechanism study indicated that the reaction is achieved by the formation of benzoyl radical from homolytic C–Co cleavage under irradiation.

Palladium-catalyzed difluorocarbene transfer enables access to enantioenriched chiral spirooxindoles

AbstractWe disclose herein an unprecedented Pd-catalyzed difluorocarbene transfer reaction, which assembles a series of structurally interesting chiral spiro ketones with generally over 90% ee. Commercially available BrCF2CO2K serves as the difluorocarbene precursor, which is harnessed as a user-friendly and safe carbonyl source in this transformation. Preliminary mechanistic studies exclude the formation of free CO in the reaction process, and importantly, we also find that BrCF2CO2K outcompete gaseous CO and several common CO surrogates in this asymmetric process. The reaction mechanism, including the in-situ progressive release of the difluorocarbene, the rapid migratory insertion of ArPd(II) = CF2 species, and subsequent defluorination hydrolysis by water to introduce the carbonyl group, accounts for the overall high efficiency and uniqueness. This work clearly showcases the advantage and potential of the difluorocarbene in synthesis and supplies a mechanistically distinct route for asymmetric carbonylative cyclization reactions.

Alder-Ene Reaction-Mediated Suppression of Tin(II) Oxidation for Efficient Tin-Lead Perovskite Solar Cells.

Despite numerous studies have reported the inhibition of tin (II) oxidation in mixed tin-lead halide perovskite, there remains a dearth of mechanistic information regarding how tin (II) undergoes oxidation in the precursor solution, particularly in terms of the involvement of DMSO. We here take advantage of density functional theory (DFT) to uncover that SnI2 can coordinate with DMSO and react with singlet oxygen, resulting in the generation of Sn (IV). Moreover, our DFT simulations reveal that benzaldehyde oxime (BZHO) competes with SnI2 in reacting with oxygen through the Alder-ene reaction, hence effectively restraining the oxidation of tin (II), which is further verified by several experimental characterizations. Besides, the introduction of BZHO has also regulated the crystallization of the perovskite film and modified the electronic structure of the perovskite surface. As a result, the perovskite solar cells with the addition of BZHO demonstrate superior performance and operational stability, retaining 82 % of the initial PCE under continuous 1-sun illumination for 800 hours. Furthermore, the efficiency of all-perovskite tandem solar cells treated with BZHO reached 26.76 %. Therefore, this work presents a promising strategy for designing high-performance and stable all-perovskite tandem solar cells.

Gold‐Catalyzed Alkoxy‐Carbonylation of Aryl and Vinyl Iodides

AbstractHerein, for the first time, we disclose the gold‐catalyzed alkoxy‐carbonylation of aryl and vinyl iodides utilizing ligand‐enabled Au(I)/Au(III) redox catalysis. The present methodology is found to be general, efficient, employs mild reaction conditions and showcases a broad substrate scope even with structurally complex molecules. Density functional theory (DFT) calculations revealed mechanistic pathways distinct from those of conventional transition metal‐catalyzed carbonylation reactions.

Gold-Catalyzed Alkoxy-Carbonylation of Aryl and Vinyl Iodides.

Herein, for the first time, we disclose the gold-catalyzed alkoxy-carbonylation of aryl and vinyl iodides utilizing ligand-enabled Au(I)/Au(III) redox catalysis. The present methodology is found to be general, efficient, employs mild reaction conditions and showcases a broad substrate scope even with structurally complex molecules. Density functional theory (DFT) calculations revealed mechanistic pathways distinct from those of conventional transition metal-catalyzed carbonylation reactions.

Palladium-catalyzed intramolecular Heck-type carbonylative cyclization cascade reaction and its application in total synthesis of complex natural products

Palladium-catalyzed intramolecular Heck-type carbonylative cyclization cascade reaction and its application in total synthesis of complex natural products