Understanding the nature of the molecular mechanisms associated with the competitive Lewis acid catalyzed [4+2] and [4+3] cycloadditions between arylidenoxazolone systems and cyclopentadiene: a DFT analysis

The molecular mechanisms of the reactions between aryliden-5(4H)-oxazolone 1, and cyclopentadiene (Cp), in presence of Lewis acid (LA) catalyst to obtain the corresponding [4+2] and [4+3] cycloadducts are examined through density functional theory (DFT) calculations at the B3LYP/6-31G* level. The activation effect of LA catalyst can be reached by two ways, that is, interaction of LA either with carbonyl or carboxyl oxygen atoms of 1 to render [4+2] or [4+3] cycloadducts. The endo and exo [4+2] cycloadducts are formed through a highly asynchronous concerted mechanism associated to a Michael-type addition of Cp to the beta-conjugated position of alpha,beta-unsaturated carbonyl framework of 1. Coordination of LA catalyst to the carboxyl oxygen yields a highly functionalized compound, 3, through a domino reaction. For this process, the first reaction is a stepwise [4+3] cycloaddition which is initiated by a Friedel-Crafts-type addition of the electrophilically activated carbonyl group of 1 to Cp and subsequent cyclization of the corresponding zwitterionic intermediate to yield the corresponding [4+3] cycloadduct. The next rearrangement is the nucleophilic trapping of this cycloadduct by a second molecule of Cp to yield the final adduct 3. A new reaction pathway for the [4+3] cycloadditions emerges from the present study.     

Computational study on the reaction mechanism of hydrosilylation of carbonyls catalyzed by high-valent rhenium(V)-di-oxo complexes

Density functional theory (DFT) calculations have been performed to elucidate the reaction mechanism of hydrosilylation of carbonyl compounds catalyzed by high-valent rhenium(V)-di-oxo complexes ReO2I(PR3)2 (R = Me, Ph). The calculations suggest that the most favorable mechanism involves the rate-determining dissociative [2 + 2] addition of the Si-H bond across a Re=O bond to form a Re(V) hydrido siloxy intermediate; this is followed by carbonyl coordination, reduction of the carbonyl, rearrangement, and final intramolecular nucleophilic attack from the alkoxy group to the silyl center (dissociative retro-[2 + 2] addition). It was also found that the additional oxo ligand in the ReO2I(PR3)2 complexes promotes the [2 + 2] addition across the rhenium-oxo bond both kinetically and thermodynamically, as compared to the neutral rhenium(V)-mono-oxo complex ReOCl3(PMe3)2. The effect of different silanes on the [2 + 2] addition barriers is also studied.     

Generation and reaction of tungsten-containing carbonyl ylides: [3 + 2]-cycloaddition reaction with electron-rich alkenes

Novel tungsten-containing carbonyl ylides 7, generated by the reaction of the o-alkynylphenyl carbonyl derivatives 1 with a catalytic amount of W(CO)(5)(thf), reacted with alkenes to give polycyclic compounds 5 through [3 + 2]-cycloaddition reaction followed by intramolecular C-H insertion of the produced nonstabilized carbene complex intermediates 8. In the presence of triethylsilane, these tungsten-containing carbene intermediates 8 were smoothly trapped intermolecularly by triethylsilane to give silicon-containing cycloadducts 17 with regeneration of the W(CO)(5) species. By this procedure, the scope of alkenes employable for this reaction was clarified. The presence of the tungsten-containing carbonyl ylide 7c was confirmed by direct observation of the mixture of o-ethynylphenyl ketone 1c and W(CO)(5)(thf-d(8)). Careful analysis of the intermediate by 2D NMR, along with the observation of the direct coupling with tungsten-183 employing the (13)C-labeled substrate, confirmed the structure of the ylide 7c. Examination using (E)- or (Z)- vinyl ether revealed that the [3 + 2]-cycloaddition reaction proceeded in a concerted manner and that the facial selectivity of the reaction differed considerably depending on the presence or absence of triethylsilane. These results clarified the reversible nature of this [3 + 2]-cycloaddition reaction.     

Calcium‐Catalyzed Formal [2+2+2] Cycloaddition

A formal intermolecular [2+2+2] cycloaddition reaction of enynes to aldehydes is presented, which can be realized in the presence of a simple and benign calcium catalyst. The reaction proceeds with excellent chemo, regio‐ and diastereoselectivity and leads to a one‐step assembly of highly interesting bicyclic building blocks containing up to three stereocenters from simple precursors via a new type of skeletal rearrangement of enynes. The observed diastereoselectivity is accounted for by two different mechanistic proposals. The first one engages mechanistic prospects arising from a gold catalyzed reaction in the absence of the stabilizing gold substituent. The second proposal involves an unprecedented cyclization–carbonyl allene ene reaction–hydroalkoxylation cascade.     

Synthesis of benzyl halide derivatives of spirohydantoins via [2+2+2] cyclotrimerization reaction

Generally, synthesis of hydantoin derivatives involve use of carbonyl compounds which in turn require multistep synthesis. Here, we report a new approach to assemble spirohydantoins via [2+2+2] cyclotrimerization reaction using commercially available, inexpensive hydantoin as a starting material.     

Ru-catalyzed intermolecular [3+2+1] cycloaddition of alpha,beta-unsaturated ketones with silylacetylenes and carbon monoxide leading to alpha-pyrones

Ruthenium catalyzes a carbonylative [3+2+1] cycloaddition, using silylacetylenes, alpha,beta-unsaturated ketones, and CO as the starting materials, providing the new method for the synthesis of tetrasubstituted alpha-pyrones. In this reaction, the carbonyl group and alpha-carbon of vinyl ketones are incorporated as a three-atom assembling unit. [reaction: see text].     

Recent advances in [2+2+2] cycloaddition reactions

The [2+2+2] cycloaddition is an elegant, atom-efficient and group tolerant process for the synthesis of carbo- and heterocycles, mostly aromatic, involving the formation of several C-C bonds in a single step. Cyclotrimerisation is catalyzed by a variety of organometallic complexes, including more than 15 different metals. The aim of this tutorial review is to point out the most recent advances in this field and to encourage the use of this reaction enroute to complex molecules. After summarizing the most common catalysts and reaction conditions generally used, we survey the mechanistic features currently accepted for this reaction. Section 4 covers the scope of the different [2+2+2] cycloaddition versions starting with the cyclotrimerisation of three triple bonds, including nitriles, with especial emphasis on asymmetric reactions that create central, axial or planar chirality. Then, reactions that use double bonds are addressed. Finally, the most outstanding examples of natural products synthesis using [2+2+2] cycloadditions as a key step reported recently are shown.     

三价磷介入的Kukhtin-Ramirez反应研究进展

Kukhtin-Ramirez反应是有机化学中一类重要的极性反转反应.利用三价磷的还原性对α-羰基酮化合物进行极性反转,所生成的Kukhtin-Ramirez活性中间体在诸多转化中都展现出了其作为1,1-偶极子的化学性质.近年来关于该活性中间体的反应研究主要包括:极性X—H键插入反应、还原性加成反应、形式[2+1]环加成反应、形式[4+1]环加成反应、形式[4+2]环加成反应.这些转化为一些重要的多官能团化合成中间体及结构复杂的环状化合物提供了高效简洁的合成方法,凸显了Kukhtin-Ramirez极性反转反应在有机合成中的重要性.     

[2+2] Cycloaddition of 1,3‐Dienes by Visible Light Photocatalysis

[2+2] Photocycloadditions of 1,3‐dienes represent a powerful yet synthetically underutilized class of reactions. We report that visible light absorbing transition metal complexes enable the [2+2] cycloaddition of a diverse range of 1,3‐dienes. The ability to use long‐wavelength visible light is attractive because these reaction conditions tolerate the presence of sensitive functional groups that might be readily decomposed by the high‐energy UVC radiation required for direct photoexcitation of 1,3‐dienes. The resulting vinylcyclobutane products are poised for a variety of further diversification reactions, and this method is consequently expected to be powerfully enabling in the synthesis of complex organic targets.     

General and Efficient Intermolecular [2+2] Photodimerization of Chalcones and Cinnamic Acid Derivatives in Solution through Visible‐Light Catalysis

[2+2] Photocycloaddition, for example, the dimerization of chalcones and cinnamic acid derivatives, is a unique strategy to construct cyclobutanes, which are building blocks for a variety of biologically active molecules and natural products. However, most attempts at the above [2+2] addition have focused on solid‐state, molten‐state, or host–guest systems under ultraviolet‐light irradiation in order to overcome the competition of facile geometric isomerization of nonrigid olefins. We report a general and simple method to realize the intermolecular [2+2] dimerization reaction of these acyclic olefins to construct cyclobutanes in a highly regio‐ and diastereoselective manner in solution under visible light, which provides an efficient solution to a long‐standing problem.     

Understanding the electronic reorganization along the nonpolar [3 + 2] cycloaddition reactions of carbonyl ylides

The nonpolar [3 + 2] cycloaddition (32CA) reaction of the carbonyl ylide (CY) 23 with tetramethylethylene (TME) 24 has been studied with DFT methods at the B3LYP/6-31G* level. This cycloaddition reaction, which has a very low activation energy of 4.7 kcal/mol, takes place through a synchronous transition structure. A topological analysis of the ELF along the 32CA reaction provides a new scope of the electronic structure of CY 23 as a pseudodiradical species offering a sound explanation of the high reactivity of this CY in nonpolar reactions. In addition, this analysis points to the nonparticipation of the oxygen lone pairs in the 32CA reaction. This cycloaddition can be seen as a pseudodiradical attack of the terminal carbon atoms of the CY 23 on the π system of TME 24. Therefore, the present study establishes that this 32CA reaction, which is not a pericyclic electron reorganization, may be electronically classified as a [2n + 2π] process.     

Structurally novel Bi- and tricyclic beta-lactams via [2 + 2] cycloaddition or radical reactions in 2-azetidinone-tethered enallenes and allenynes

[reaction: see text] Thermolysis of beta-lactam-tethered enallenyl alcohols gave tricyclic ring structures via a formal [2 + 2] cycloaddition of the alkene with the distal bond of the allene, while the tin-promoted radical cyclization in 2-azetidinone-tethered allenynes proceeded to provide bicyclic beta-lactams containing a medium-sized ring. The access to cyclization precursors was achieved by regio- and stereoselective metal-mediated carbonyl allenylation of 4-oxoazetidine-2-carbaldehydes in an aqueous environment.     

Polar [3 + 2] cycloaddition of ketones with electrophilically activated carbonyl ylides. Synthesis of spirocyclic dioxolane indolinones

The [3 + 2] cycloaddition reaction between carbonyl ylides generated from epoxides and ketones (ethyl pyruvate, ethyl phenylglyoxylate, isatin, N-methylisatin and 5-chloroisatin) to give substituted dioxolanes and spirocyclic dioxolane indolinones was investigated. The effect of microwave irradiation on the outcome of the reaction was studied. The thermal reaction between 2,2-dicyano-3-phenyloxirane and N-methylisatin was theoretically studied using DFT methods. This reaction is a domino process that comprises two steps. The first is the thermal ring opening of the epoxide to yield a carbonyl ylide intermediate, whereas the second step is a polar [3 + 2] cycloaddition to yield the final spiro cycloadducts. The cycloaddition presents a low stereoselectivity and a large regio- and chemoselectivity. Analysis of the electrophilicity values and the Fukui functions of the reagents involved in the cycloaddition step allowed the chemical outcome to be explained.     

Photocatalytic [2 + 2] cycloadditions of enones with cleavable redox auxiliaries

α,β-Unsaturated 2-imidazolyl ketones undergo [2 + 2] cycloaddition with a variety of Michael acceptors upon irradiation with visible light in the presence of Ru(bpy)(3)(2+). Cleavage of the imidazolyl auxiliary from the cycloadducts affords cyclobutane carboxamides, esters, thioesters, and acids that would not be accessible from direct cycloaddition of the corresponding unsaturated carbonyl compounds.     

[2 + 2]-Cycloreversions

Four-membered rings can be cleaved thermally, Photochemically, or catalytically into two π bonded fragments. Theoretical calculations, kinetic studies, and investigations of stereo- and regioselectivity have been undertaken to clarify the question of whether the reaction involves one or two steps and to permit predictions on its course. [2 + 2]-Cycloreversions have been used to clarify the structure of four-membered rings, to prepare highly reactive π electron-systems and–in combination with a [2 + 2]-cycloaddition–to protect double bonds. The combination of a cycloaddition and-reversion can be used to convert a carbonyl group into an olefin. Starting with compounds containing annelated four-membered rings, compounds with two functional groups or large ring systems can be prepared. [2 + 2]-Cycloreversions have also been discussed in connection with storage of solar energy.     

Efficient visible light photocatalysis of [2+2] enone cycloadditions

We report that Ru(bipy)3Cl2 can serve as a visible light photocatalyst for [2+2] enone cycloadditions. A variety of aryl enones participate readily in the reaction, and the diastereoselectivity in the formation of the cyclobutane products is excellent. We propose a mechanism in which a photogenerated Ru(bipy)3+ complex promotes one-electron reduction of the enone substrate, which undergoes subsequent radical anion cycloaddition. The efficiency of this process is extremely high, which allows rapid, high-yielding [2+2] cyclizations to be conducted using incident sunlight as the only source of irradiation.     

Co-Catalyzed Asymmetric Intramolecular [3+2] Cycloaddition of Yne-Alkylidenecyclopropanes and its Reaction Mechanism

Developing new transition metal-catalyzed asymmetric cycloadditions for the synthesis of five-membered carbocycles (FMCs) is a research frontier in reaction development due to the ubiquitous presence of chiral FMCs in various functional molecules. Reported here is our discovery of a highly enantioselective intramolecular [3+2] cycloaddition of yne-alkylidenecyclopropanes (yne-ACPs) to bicyclo[3.3.0]octadiene and bicyclo[4.3.0]nonadiene molecules using a cheap Co catalyst and commercially available chiral ligand (S)-Xyl-BINAP. This reaction avoids the use of precious Pd and Rh catalysts, which are usually the choices for [3+2] reactions with ACPs. The enantiomeric excess in the present reaction can be up to 92 %. Cationic cobalt(I) species was suggested by experiments as the catalytic species. DFT calculations showed that this [3+2] reaction starts with oxidative cyclometallation of alkyne and ACP, followed by ring opening of the cyclopropyl (CP) group and reductive elimination to form the cycloadduct. This mechanism is different from previous [3+2] reactions of ACPs, which usually start from CP cleavage, not from oxidative cyclization.     

A photocatalytic acid- and base-free Meerwein-Ponndorf-Verley-type reduction using a [Ru(bpy)3]2+/viologen couple

A photocatalytic system to effect the Meerwein-Ponndorf-Verley reduction of carbonylic compounds to alcohols has been developed. The system comprises [Ru(bpy)3]2+ as a photosensitizer, triethanolamine as a sacrificial electron donor, viologen as an electron acceptor, and the carbonyl compound and iPrOH as Meerwein-Ponndorf-Verley reagents. The photocatalytic reaction can be performed in neat iPrOH or in 1-butyl-3-methylimidazolium ionic liquid. Mass spectrometric detection of the viologen hydride derivative VH+ confirms that this species is the reducing agent responsible for the carbonyl compound reduction. The reaction intermediates involved in the photocatalytic system have also been characterized by laser flash photolysis.     

Solid-supported [2+2+2] cyclotrimerizations

The transition-metal-catalyzed [2+2+2] cyclotrimerization of a diyne and an alkyne provides a convergent route to highly-substituted aromatic rings. This reaction possesses distinct drawbacks, especially low chemo- and regioselectivities, which hamper its application in combinatorial synthesis. These problems have been solved by the development of solid-supported [2+2+2]-cycloaddition reactions. If conducted on a solid-support, this reaction enables rapid combinatorial access to diverse sets of carbo- and heterocyclic small-molecule arrays. The scope of this methodology has been investigated by examining different immobilization strategies, different diyne precursors, and a variety of functionalized alkyne reaction partners. Overall, isoindoline, phthalan, and indan libraries were assembled in good to excellent yields and with high purities.     

Platinum(II)-catalyzed reaction of 2-alkynylbenzoates or benzothioates with vinyl ethers: a concise method for synthesis of 1-acyl-4-alkoxy- or 1-acyl-4-alkylsulfanylnaphthalene derivatives

[reaction: see text] A concise method for the preparation of 1-acyl-4-alkoxy- or 1-acyl-4-alkylsulfanylnaphthalenes has been developed by the reaction of o-ethynylbenzoates or benzothioates with vinyl ethers, in the presence of a catalytic amount of PtCl(2). It is proposed that the reaction proceeds through [3 + 2]-cycloaddition of the platinum-containing carbonyl ylides followed by 1,2-alkyl migration.