Carbonyl-olefin Metathesis Reactions Research Articles

Catalytic, Interrupted Carbonyl-Olefin Metathesis for the Formation of Functionalized Cyclopentadienes

Cyclopentadienes are scaffolds in organometallic chemistry, synthetic organic chemistry, and catalysis. We herein describe a regioselective Lewis-acid-catalyzed method for the synthesis of highly functionalized cyclopentadienes incorporating electronically and sterically diverse subunits. Our experimental and theoretical investigations support a mechanism that is related to catalytic carbonyl-olefin metathesis reactions wherein Lewis-acid-catalyzed cycloadditions between carbonyl and alkene functionalities afford reactive oxetane intermediates. However, in lieu of a [2+2]-cycloreversion, stepwise oxetane fragmentation to intermediate carbocations results in the formation of functionalized cyclopentadienes via interrupted carbonyl-olefin metathesis. This work provides insights into the design of catalytic carbonyl-olefin metathesis reactions of aliphatic ketone substrates as stepwise oxetane fragmentation was previously only reported as a competing reaction pathway for aryl ketones.

Toward Homogeneous Brønsted-Acid-Catalyzed Intramolecular Carbonyl-Olefin Metathesis Reactions.

The carbonyl-olefin metathesis (COM) reaction is an attractive approach for the formation of a new carbon-carbon double bond from a carbonyl precursor. In principle, this reaction can be promoted by the activation of the carbonyl group with a Brønsted acid catalyst; however, it is often complicated as a result of unwanted side reactions under acidic conditions. Thus, there have been only a very few examples of Brønsted-acid-catalyzed COM reactions, all of which required specially designed setups. Herein, we report a new practical homogeneous Brønsted-acid-catalyzed protocol using nitromethane, a readily available solvent, to promote intramolecular ring-closing COM reactions.

Hydrogen Bonding Networks Enable Brønsted Acid-Catalyzed Carbonyl-Olefin Metathesis.

Synthetic chemists have learned to mimic nature in using hydrogen bonds and other weak interactions to dictate the spatial arrangement of reaction substrates and to stabilize transition states to enable highly efficient and selective reactions. The activation of a catalyst molecule itself by hydrogen‐bonding networks, in order to enhance its catalytic activity to achieve a desired reaction outcome, is less explored in organic synthesis, despite being a commonly found phenomenon in nature. Herein, we show our investigation into this underexplored area by studying the promotion of carbonyl‐olefin metathesis reactions by hydrogen‐bonding‐assisted Brønsted acid catalysis, using hexafluoroisopropanol (HFIP) solvent in combination with para‐toluenesulfonic acid (pTSA). Our experimental and computational mechanistic studies reveal not only an interesting role of HFIP solvent in assisting pTSA Brønsted acid catalyst, but also insightful knowledge about the current limitations of the carbonyl‐olefin metathesis reaction.

Carbonyl-Olefin Metathesis.

This Review describes the development of strategies for carbonyl-olefin metathesis reactions relying on stepwise, stoichiometric, or catalytic approaches. A comprehensive overview of currently available methods is provided starting with Paternò-Büchi cycloadditions between carbonyls and alkenes, followed by fragmentation of the resulting oxetanes, metal alkylidene-mediated strategies, [3 + 2]-cycloaddition approaches with strained hydrazines as organocatalysts, Lewis acid-mediated and Lewis acid-catalyzed strategies relying on the formation of intermediate oxetanes, and protocols based on initial carbon-carbon bond formation between carbonyls and alkenes and subsequent Grob-fragmentations. The Review concludes with an overview of applications of these currently available methods for carbonyl-olefin metathesis in complex molecule synthesis. Over the past eight years, the field of carbonyl-olefin metathesis has grown significantly and expanded from stoichiometric reaction protocols to efficient catalytic strategies for ring-closing, ring-opening, and cross carbonyl-olefin metathesis. The aim of this Review is to capture the status quo of the field and is expected to contribute to further advancements in carbonyl-olefin metathesis in the coming years.

Iron-Catalyzed Carbonyl–Alkyne and Carbonyl–Olefin Metathesis Reactions

Construction of carbon–carbon bonds is one of the most important tools for the synthesis of complex organic molecules. Among multiple possibilities are the carbonyl–alkyne and carbonyl–olefin metathesis reactions, which are used to form new carbon–carbon bonds between carbonyl derivatives and unsaturated organic compounds. As many different approaches have already been established and offer reliable access to C=C bond formation via carbonyl–alkyne and carbonyl–olefin metathesis, focus is now shifting towards cost efficiency, sustainability and environmentally friendly metal catalysts. Iron, which is earth-abundant and considered as an eco-friendly and inexpensive option in comparison to traditional metal catalysts, fulfils these requirements. Hence, the focus of this review is on recent advances in the iron-catalyzed carbonyl–alkyne, carbonyl–olefin and related C–O/C–O metathesis reactions. The still large research potential for ecologically and economically attractive and sustainable iron-based catalysts is demonstrated.

Superelectrophilic aluminium(iii)–ion pairs promote a distinct reaction path for carbonyl–olefin ring-closing metathesis

Catalytic carbonyl–olefin metathesis reactions represent powerful synthetic strategies for alkene formation. Successful approaches for carbonyl–olefin ring-closing, ring-opening and cross metathesis have been developed in recent years, but current limitations hamper the generality of these transformations. Stronger, more efficient catalytic systems are needed to further broaden the scope of these transformations while they prevent undesired reaction pathways. Here we report the development of an aluminium-based heterobimetallic ion pair as a superior catalyst that promotes carbonyl–olefin ring-closing metathesis via a distinct reaction mechanism and allows access to six- and seven-membered rings, which suffer from low yields and poor conversion under previously reported conditions. Mechanistic investigations support a distinct reaction profile in which two productive reaction pathways competitively form metathesis products. These insights are expected to have important implications in the catalyst design and development for carbonyl–olefin metathesis and enable future advances to ultimately expand the synthetic utility of these transformations. Carbonyl–olefin metathesis reactions are a valuable tool in synthetic chemistry, but there are still some limitations in scope. Now, a catalyst system allows the activation of previously unreactive substrates for such a reaction by aluminium(iii)–ion pairs acting as Lewis acidic superelectrophiles.

Catalytic Alkyne/Alkene-Carbonyl Metathesis: Towards the Development of Green Organic Synthesis

The construction of carbon-carbon bond through the metathesis reactions between carbonyls and olefins or alkynes has attracted significant interest in organic chemistry due to its high atomeconomy and efficiency. In this regard, carbonyl–alkyne metathesis is well developed and widely used in organic synthesis for the atom-efficient construction of various carbocycles and heterocycles in the presence of catalytic Lewis acids or Brønsted acids. On the other hand, alkene-carbonyl metathesis is recently developed and has been a topic of great importance in the field of organic chemistry because they possess attractive qualities involving metal-mediated, metal-free intramolecular, photochemical, Lewis acid-mediated ring-closing metathesis, ring-opening metathesis and cross-metathesis. This review covers most of the strategies of carbonyl–alkyne and carbonyl–olefin metathesis reactions in the synthesis of complex molecules, natural products and pharmaceuticals as well as provides an overview of exploration of the metathesis reactions with high atom-economy as well as environmentally and ecologically benign reaction conditions.

Superelectrophilic Fe(III)-Ion Pairs as Stronger Lewis Acid Catalysts for (E)-Selective Intermolecular Carbonyl-Olefin Metathesis.

An intermolecular carbonyl-olefin metathesis reaction is described that relies on superelectrophilic Fe(III)-based ion pairs as stronger Lewis acid catalysts. This new catalytic system enables selective access to (E)-olefins as carbonyl-olefin metathesis products. Mechanistic investigations suggest the regioselective formation and stereospecific fragmentation of intermediate oxetanes to be the origin of this selectivity. The optimized conditions are general for a variety of aryl aldehydes and trisubstituted olefins and are demonstrated for 28 examples in up to 64% overall yield.

Models for Understanding Divergent Reactivity in Lewis Acid-Catalyzed Transformations of Carbonyls and Olefins

Carbonyl–ene, Prins, and carbonyl–olefin metathesis reactions represent powerful strategies for carbon–carbon bond formation relying on Lewis acid catalysts. Although common Lewis acids are able to...

AuCl3 -Catalyzed Ring-Closing Carbonyl-Olefin Metathesis.

Compared with the ripeness of olefin metathesis, exploration of the construction of carbon-carbon double bonds through the catalytic carbonyl-olefin metathesis reaction remains stagnant and has received scant attention. Herein, a highly efficient AuCl3 -catalyzed intramolecular ring-closing carbonyl-olefin metathesis reaction is described. This method features easily accessible starting materials, simple operation, good functional-group tolerance and short reaction times, and provides the target cyclopentenes, polycycles, benzocarbocycles, and N-heterocycle derivatives in good to excellent yields.

Intermolecular Carbonyl–olefin Metathesis with Vinyl Ethers Catalyzed by Homogeneous and Solid Acids in Flow

AbstractThe carbonyl–olefin metathesis reaction has experienced significant advances in the last seven years with new catalysts and reaction protocols. However, most of these procedures involve soluble catalysts for intramolecular reactions in batch. Herein, we show that recoverable, inexpensive, easy to handle, non‐toxic, and widely available simple solid acids, such as the aluminosilicate montmorillonite, can catalyze the intermolecular carbonyl–olefin metathesis of aromatic ketones and aldehydes with vinyl ethers in‐flow, to give alkenes with complete trans stereoselectivity on multi‐gram scale and high yields. Experimental and computational data support a mechanism based on a carbocation‐induced Grob fragmentation. These results open the way for the industrial implementation of carbonyl–olefin metathesis over solid catalysts in continuous mode, which is still the origin and main application of the parent alkene–alkene cross‐metathesis.

Intermolecular Carbonyl-olefin Metathesis with Vinyl Ethers Catalyzed by Homogeneous and Solid Acids in Flow.

The carbonyl-olefin metathesis reaction has experienced significant advances in the last seven years with new catalysts and reaction protocols. However, most of these procedures involve soluble catalysts for intramolecular reactions in batch. Herein, we show that recoverable, inexpensive, easy to handle, non-toxic, and widely available simple solid acids, such as the aluminosilicate montmorillonite, can catalyze the intermolecular carbonyl-olefin metathesis of aromatic ketones and aldehydes with vinyl ethers in-flow, to give alkenes with complete trans stereoselectivity on multi-gram scale and high yields. Experimental and computational data support a mechanism based on a carbocation-induced Grob fragmentation. These results open the way for the industrial implementation of carbonyl-olefin metathesis over solid catalysts in continuous mode, which is still the origin and main application of the parent alkene-alkene cross-metathesis.

Iodonium-Catalyzed Carbonyl–Olefin Metathesis Reactions

The carbonyl–olefin metathesis reaction has become increasingly important in organic synthesis due to its versatility in functional group interconversion chemistry. Recent developments in the field have identified a number of transition-metal and organic Lewis acids as effective catalysts for this reaction. Herein, we report the use of simple organic compounds such as N-iodosuccinimide or iodine monochloride to catalyze the carbonyl–olefin metathesis process under mild reaction conditions. This work broadens the scope of this chemical transformation to include iodonium sources as simple and practical catalysts.

Development of a Hydrazine-Catalyzed Carbonyl-Olefin Metathesis Reaction

Carbonyl-olefin metathesis is a potentially powerful yet underexplored reaction in organic synthesis. In recent years, however, this situation has begun to change, most notably with the introduction of several different catalytic technologies. The development of one of those new strategies, based on hydrazine catalysts and a novel [3+2] paradigm for double bond metathesis, is discussed herein. First, the stage is set with a description of some potential applications of carbonyl-olefin metathesis and a discussion of alternative strategies for this intriguing reaction.1 Introduction2 Potential Applications of Carbonyl-Olefin Metathesis3 Carbonyl-Olefin Metathesis Strategies4 Direct (Type I): Non-Catalytic5 Direct (Type I): Acid-Catalyzed6 Indirect (Type II): Metal Alkylidenes7 Indirect (Type III): Hydrazine-Catalyzed8 Conclusion

Lewis Acid-Catalyzed Carbonyl–Olefin Metathesis

Catalytic carbonyl-olefin metathesis reactions enable direct carbon-carbon bond formation between carbonyl and olefin substrates relying on carbonyl-activation with a suitable Lewis acid. Based on this reaction design principle, efficient protocols for intermolecular carbonyl-olefin metathesis, as well as ring-closing and ring-opening carbonyl-olefin metathesis have been developed.

Recent advances in the application of ring-closing metathesis for the synthesis of unsaturated nitrogen heterocycles.

This short review summarizes recent advances relating to the application of ring-closing olefin-olefin and carbonyl-olefin metathesis reactions towards the synthesis of unsaturated five- and six-membered nitrogen heterocycles. These developments include catalyst modifications and reaction designs that will enable access to more complex nitrogen heterocycles.

Catalytic, transannular carbonyl-olefin metathesis reactions.

Transannular carbonyl-olefin metathesis reactions complement existing procedures for related ring-closing, ring-opening, and intermolecular carbonyl-olefin metathesis. We herein report the development and mechanistic investigation of FeCl3-catalyzed transannular carbonyl-olefin metathesis reactions that proceed via a distinct reaction path compared to previously reported ring-closing and ring-opening protocols. Specifically, carbonyl-ene and carbonyl-olefin metathesis reaction pathways are competing under FeCl3-catalysis to ultimately favor metathesis as the thermodynamic product. Importantly, we show that distinct Lewis acid catalysts are able to distinguish between these pathways to enable the selective formation of either transannular carbonyl-ene or carbonyl-olefin metathesis products. These insights are expected to enable further advances in catalyst design to efficiently differentiate between these two competing reaction paths of carbonyl and olefin functionalities to further expand the synthetic generality of carbonyl-olefin metathesis.

Catalytic Carbonyl-Olefin Metathesis of Aliphatic Ketones: Iron(III) Homo-Dimers as Lewis Acidic Superelectrophiles.

Catalytic carbonyl-olefin metathesis reactions have recently been developed as a powerful tool for carbon-carbon bond formation. However, currently available synthetic protocols rely exclusively on aryl ketone substrates while the corresponding aliphatic analogs remain elusive. We herein report the development of Lewis acid-catalyzed carbonyl-olefin ring-closing metathesis reactions for aliphatic ketones. Mechanistic investigations are consistent with a distinct mode of activation relying on the in situ formation of a homobimetallic singly bridged iron(III)-dimer as the postulated active catalytic species. These "superelectrophiles" function as more powerful Lewis acid catalysts that form upon association of individual iron(III)-monomers. While this mode of Lewis acid activation has previously been postulated to exist, it has not yet been applied in a catalytic setting. The insights presented are expected to enable further advancement in Lewis acid catalysis by building upon the activation principle of "superelectrophiles" and to broaden the current scope of catalytic carbonyl-olefin metathesis reactions.

Carbonyl–Olefin Metathesis Catalyzed by Molecular Iodine

The carbonyl–olefin metathesis reaction could facilitate rapid functional group interconversion and allow construction of complicated organic structures. Herein, we demonstrate that elemental iodine, a very simple catalyst, can efficiently promote this chemical transformation under mild reaction conditions. Our mechanistic studies revealed intriguing aspects of the activation mode via molecular iodine and the iodonium ion that could change the previously established perception of catalyst and substrate design for the carbonyl–olefin metathesis reaction.

Tropylium-promoted carbonyl-olefin metathesis reactions.

The carbonyl-olefin metathesis (COM) reaction is a highly valuable chemical transformation in a broad range of applications. However, its scope is much less explored compared to analogous olefin-olefin metathesis reactions. Herein we demonstrate the use of tropylium ion as a new effective organic Lewis acid catalyst for both intramolecular and intermolecular COM and new ring-opening metathesis reactions. This represents a significant improvement in substrate scope from recently reported developments in this field.