NHC-catalyzed enantioselective [2 + 2] and [2 + 2 + 2] cycloadditions of ketenes with isothiocyanates

The enantioselective N-heterocyclic carbene-catalyzed formal [2 + 2] and [2 + 2 + 2] cycloaddition of ketenes and isothiocyanates were developed. Reaction with N-aryl isothiocyanates at room temperature favors the [2 + 2] cycloaddition, while reaction with N-benzoyl isothiocyanates at -40 °C favors the [2 + 2 + 2] cycloaddition.     

Rhodium N-heterocyclic carbene-catalyzed [4 + 2] and [5 + 2] cycloaddition reactions

[reactions: see text] A rhodium complex of N-heterocyclic carbene (NHC) has been developed for intra- and intermolecular [4 + 2] and intramolecular [5 + 2] cycloaddition reactions. This is the first use of a transition-metal NHC complex in a Diels-Alder-type reaction. For the intramolecular [4 + 2] cycloaddition reactions, all the dienynes studied were converted to their corresponding cycloadducts in 91-99% yields within 10 min. Moreover, up to 1900 turnovers have been obtained for the intramolecular [4 + 2] cycloaddition at 15-20 degrees C. For the intermolecular [4 + 2] cycloadditions, high yields (71-99%) of the corresponding cycloaddition products were obtained. The reaction time and yield were highly dependent upon the diene and the dienophile. For the intramolecular [5 + 2] cycloaddition reactions, all the alkyne vinylcyclopropanes studied were converted to their corresponding cycloadducts in 91-98% yields within 10 min. However, the catalytic system was not effective for an intermolecular [5 + 2] cycloaddition reaction.     

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.     

Intramolecular pyridone/enyne photocycloaddition: partitioning of the [4 + 4] and [2 + 2] pathways

Intramolecular photocycloaddition (>290 nm) between a 1,3-enyne and a 2-pyridone is far more selective than the intermolecular version; a three-atom linkage both controls regiochemistry and separates the [2 + 2] and [4 + 4] pathways. All four head-to-head, head-to-tail, tail-to-head, and tail-to-tail tetherings have been investigated. Linkage via the ene of the enyne leads to [2 + 2] products regardless of alkene geometry, whereas linkage through the yne results in [4 + 4] cycloadducts. The bridged 1,2,5-cyclooctatriene products of [4 + 4] cycloaddition are unstable and undergo a subsequent [2 + 2] dimerization reaction.     

Mechanistic twist of the [8+2] cycloadditions of dienylisobenzofurans and dimethyl acetylenedicarboxylate: stepwise [8+2] versus [4+2]/[1,5]-vinyl shift mechanisms revealed through a theoretical and experimental study

Recently, it was reported that both dienylfurans and dienylisobenzofurans could react with dimethyl acetylenedicarboxylate (DMAD) to give [8+2] cycloadducts. Understanding these [8+2] reactions will aid the design of additional [8+2] reactions, which have the potential for the synthesis of 10-membered and larger carbocycles. The present Article is aimed to understand the detailed mechanisms of the originally reported [8+2] cycloaddition reaction between dienylisobenzofurans and alkynes at the molecular level through the joint forces of computation and experiment. Density functional theory calculations at the (U)B3LYP/6-31+G(d) level suggest that the concerted [8+2] pathway between dienylisobenzofurans and alkynes is not favored. A stepwise reaction pathway involving formation of a zwitterionic intermediate for the [8+2] reactions between dienylisobenzofurans that contain electron-donating methoxy groups present in their diene moieties and DMAD has been predicted computationally. This pathway is in competition with a Diels-Alder [4+2] reaction between the furan moieties of dienylisobenzofurans and DMAD. When there is no electron-donating group present in the diene moieties of dienylisobenzofurans, the [8+2] reaction occurs through an alternative mechanism involving a [4+2] reaction between the furan moiety of the tetraene and DMAD, followed by a [1,5]-vinyl shift. This computationally predicted novel mechanism was supported experimentally.     

Photochemically induced [4+2]- versus [3+2]-cycloreversion reaction of hexasubstituted 2,3-diaza-bicyclo[3.1.0]hex-2-enes

Hexasubstituted 2,3-diaza-bicyclo[3.1.0]hex-2-enes containing large substituents at C-4 and C-6 upon irradiation undergo a novel [4+2]cycloreversion reaction leading to 2,3-diazahexatriens besides the normal [3+2]cycloreversion.     

[7+2]- and [11+2]-cycloaddition reactions of diazo-azoles with isocyanates to azolo[5,1-d] [1,2,3,5] tetrazine-4-ones

Diazo-azoles react as 1,7- or 1,11-dipoles with isocyanates to form the hitherto unknown pyrazolo[5,1-d] [1,2,3,5]tetrazine-4-ones, [1,2,3,5]tetrazino[5,4-b]indazole-4-ones and [1,2,3]triazolo[5,1-d][1,2,3,5]tetrazine-4-ones in a [7+2]- or [11+2]-cycloaddition reaction.     

Transition metal-catalyzed [4 + 2 + 2] cycloadditions of bicyclo[2.2.1]hepta-2,5-dienes (norbornadienes) and bicyclo[2.2.2]octa-2,5-dienes

The transition-metal-catalyzed [4 + 2 + 2] cycloadditions of norbornadienes, bicyclo[2.2.2]octa-2,5-diene, and benzobarrelene with 1,3-butadienes proceed in excellent yields using cobalt-based catalytic systems. Two key distinctions between these [4 + 2 + 2] cycloadditions and the corresponding transition-metal-catalyzed [2 + 2 +2] reactions of norbornadiene are the requirement of a bimetal catalytic system with a bisphosphine ligand for the former and exclusive regioselectivity in the [4 + 2 + 2] reaction of 2-substituted norbornadienes to produce 1-substituted adducts. These distinctions may indicate two distinct mechanisms for the [4 + 2 + 2] and [2 + 2 + 2] reactions.     

[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.     

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.     

Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.     

Transition metal-catalyzed intermolecular [5+2] and [5+2+1] cycloadditions of allenes and vinylcyclopropanes

Initial examples of the intermolecular Rh(I)-catalyzed [5+2] cycloaddition reaction of bifunctional allenes and vinylcyclopropanes are described. The reactions proceed with facility and in yields of up to 99% with a variety of alkyne-, ester-, styrene-, or cyano-substituents on the allene to afford the corresponding cycloadducts. In the presence of CO, the reaction proceeds to an eight-membered ring cycloadduct and its transannularly closed product, providing the first example of a three-component [5+2+1] cycloaddition with allenes.     

Charge transfer chromophore-stopped [2]rotaxane through [2 + 2] cycloaddition

Three charge-transfer chromophore-terminated [2]rotaxanes were synthesized, using a high-yield [2 + 2]cycloaddition reaction in apolar solvent at room temperature. Two solvent-driving molecular shuttles were constructed, which exhibit distinct conformations in different solvent as a result of the shuttling movement of the macrocycle.     

过渡金属催化[2 + 2 + 2]环加成反应合成吡啶衍生物

环加成反应可以一步同时构建多个化学键,是目前国内外研究最为活跃的领域之一。相比于传统方法,过渡金属催化的[2+2+2]环加成反应是合成吡啶衍生物的有效手段。本文从反应机理、非手性吡啶化合物合成和手性吡啶化合物合成三个方面阐述了近年来吡啶衍生物的研究情况,涉及Co、Rh、Ru、Fe、Ni、Ti等金属催化体系。     

Diastereoselective synthesis of five- and seven-membered rings by [2+2+1], [3+2], [3+2+2], and [4+3] carbocyclization reactions of beta-substituted (alkenyl)(methoxy)carbene complexes with methyl ketone lithium enolates

beta-Substituted alkenylcarbene complexes react with methyl ketone lithium enolates to give different carbocyclization products depending on the structure of the lithium enolate, on the metal of the carbene complex, and on the reaction media. Thus, the reactions of aryl and alkyl methyl ketone lithium enolates with beta-substituted alkenyl chromium and tungsten carbene complexes in diethyl ether afford 1,3-cyclopentanediol derivatives derived from a formal [2+2+1] carbocyclization reaction. However, the lithium enolates of acetone and tungsten complexes furnish formal [3+2+2] carbocyclization products. In the case of alkynyl methyl ketone lithium enolates, competitive formal [2+2+1] and [3+2] carbocyclization reactions occur and 1,3-cyclopentanediol and 3-cyclopentenol derivatives are formed. Conversely, alkenyl methyl ketone lithium enolates react with alkenylcarbene complexes under the same reaction conditions to form 2-cycloheptenone derivatives by a formal [4+3] carbocyclization reaction. Finally, when the reaction was performed in the presence of a coordinating medium, the [3+2] carbocyclization pattern was observed independently of the nature of the methyl ketone lithium enolate used.     

Phenanthridine synthesis via [2+2+2] cyclotrimerization reactions

A concise synthesis of phenanthridines via a microwave-assisted [2+2+2] cyclotrimerization reaction has been developed.     

Photosensitized [4+2]- and [2+2]-Cycloaddition Reactions of N-Sulfonylimines

The synthesis of polycyclic compounds is of high interest due to the prevalence of these motifs in drugs and natural products. Herein, we report on the stereoselective construction of 3D bicyclic scaffolds and azetidine derivatives by modulation of N-sulfonylimines to achieve either [4+2]- or [2+2]-cycloaddition reactions. The utility of the method was established by further modulation of the product. Mechanistic studies are also included, which support reaction via Dexter energy transfer.     

Formal [3 + 2] and [3 + 3] additions of acceptor-substituted cyclopropylmethylsilanes to allenylsilanes

1,3-Dipolar synthons formed from vicinal TBDPS-substituted cyclopropyl alkyl/phenyl ketones on treatment with Lewis acids such as TiCl(4) and Et(2)AlCl reacted with allenylsilanes to furnish [3 + 2] and [3 + 3] adducts with high regio- and stereocontrol. [reaction: see text]     

Intramolecular ketenimine-ketenimine [2 + 2] and [4 + 2] cycloadditions

Bis(ketenimines), in which the two heterocumulenic functions are placed in close proximity on a carbon skeleton to allow their mutual interaction, show a rich and not easily predictable chemistry. Intramolecular [2 + 2] or [4 + 2] cycloadditions are, respectively, observed when both ketenimine functions are supported on either ortho-benzylic or 2,2'-biphenylenic scaffolds. In addition, nitrogen-to-carbon [1,3] and [1,5] shifts of arylmethyl groups in N-arylmethyl-C,C-diphenyl ketenimines are also disclosed.