Multicomponent cycloadditions: the four-component [5+1+2+1] cycloaddition of vinylcyclopropanes, alkynes, and CO

Prompted by the view that intermediates of transition metal-catalyzed reactions could be intercepted by one or more additional components, studies in our laboratory have led to the design and development of new three-component [5+2+1], [4+2+1], and [2+2+1] cycloadditions. These continuing studies have now led to the identification of a fundamentally new four-component [5+1+2+1] cycloaddition reaction of vinylcyclopropanes, alkynes and CO, yielding hydroxyindanone products in generally good yields. Terminal alkynes bearing aryl or alkyl groups are tolerated well. Substitution at any position of the VCP leads predictably to substituted hydroxyindanone products. Using a bis-alkynyl substrate, the reaction can be carried out bi-directionally, forming 10 C-C bonds and four new rings from seven components in a single, operationally simple process.     

Tethered 2 + 2 + 2 cycloaddition reactions of cobalt-cycloheptyne complexes

Cycloheptyne-dicobalt hexacarbonyl complexes, substituted by propargylic ether functions, undergo 2 + 2 + 2 cycloaddition reactions with alkynes to give tricyclic benzocycloheptanes; an all-intramolecular version of this transformation is also possible.     

Concerted Catalysis by Adjacent Palladium and Gold in Alloy Nanoparticles for the Versatile and Practical [2+2+2] Cycloaddition of Alkynes

A Pd‐Au alloy efficiently catalyzed the [2+2+2] cycloaddition of substituted alkynes. Whereas monometallic Pd and Au catalysts were totally ineffective, Pd‐Au alloy nanoparticle catalysts with a low Pd/Au molar ratio showed high activity to give the corresponding polysubstituted arenes in high yields. A variety of substituted alkynes participated in various modes of cycloaddition under Pd‐Au alloy catalysis. The Pd‐Au alloy catalysts exhibited high air tolerance and reusability.     

Synthesis of silafluorenes by iridium-catalyzed [2 + 2 + 2] cycloaddition of silicon-bridged diynes with alkynes

[reaction: see text] Silicon-bridged 1,6-diynes underwent [2 + 2 + 2] cycloaddition with alkynes in the presence of an iridium(I)-phosphine catalyst to afford densely substituted silafluorene derivatives. Extended silafluorene skeletons were constructed by the [2 + 2 + 2] cycloaddition of tetraynes.     

Nickel-mediated regioselective [2 + 2 + 2] cycloaddition of carboryne with alkynes

Transition metal-benzyne complexes have found many applications in organic synthesis, mechanistic studies, and the synthesis of functional materials. In sharp contrast, the chemistry of transition metal-carboryne complexes, especially late transition metal complexes, is virtually unknown. This communication reports a novel nickel-mediated regioselective [2 + 2 + 2] cycloaddition reaction of carboryne with alkynes via the Ni-carboryne intermediate (eta2-C2B10H10)Ni(PPh3)2. Because of the bulkiness of the carborane moiety, a high regioselectivity was achieved in the reactions involving unsymmetrical alkynes. This work furnishes a novel method for the preparation of highly substituted benzocarboranes which are difficult to obtain by other methods.     

Ruthenium-catalyzed regioselective [2 + 2 + 2] cyclotrimerization of trifluoromethyl group substituted internal alkynes

It found that the Ru(3)(CO)(12) coordinated with 2-(diphenylphosphino)benzonitrile (2-DPPBN) to effectively catalyze the [2 + 2 + 2] cyclotrimerization of the trifluoromethyl group substituted internal alkynes in high yields with up to >98% regioselectivity. Isolation of a ruthenacyclopentadiene was successful and confirmed that the complex is a reaction intermediate.     

One-pot synthesis of substituted benzene via intermolecular [2+2+2] cycloaddition catalyzed by air-stable Ru(II)-complex

Intermolecular [2+2+2] cycloaddition reaction employing an air-stable ruthenium perchloro-cyclobutenonyl complex as a catalyst is reported. A series of internal alkynes were incorporated with dimethyl acetylene-dicarboxylate in a ratio of 1:2 to give various substituted benzenes in high yield and high chemoselectivity.     

Rhodium(I)-catalyzed [4+2+2] cycloadditions of 1,3-dienes, alkenes, and alkynes for the synthesis of cyclooctadienes

The first [4+2+2] cycloadditions involving terminal alkynes and diene-enes, including a fully intramolecular example, are reported resulting in the formation of cyclooctadienes using [RhCl(CO)2]2 (5 mol %) treated with AgSbF6 (10 mol %) as a precatalyst. The reaction is general for a variety of terminal alkynes, as well as variously substituted diene-enes (yields up to 88%).     

Metal‐Free Synthesis of Highly Substituted Pyridines by Formal [2+2+2] Cycloaddition under Mild Conditions

The synthesis of pyridines through direct intermolecular cycloaddition of alkynes and nitriles is a contemporary challenge in organic synthesis. A Brønsted acid mediated formal [2+2+2] cycloaddition of heteroalkynes and nitriles was developed that proceeds under mild conditions. This constitutes a modular approach to highly substituted pyridine cores.     

Rhodium-catalyzed [2 + 2 + 2] cycloaddition of alkenyl isocyanates and alkynes

A rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition between alkenyl isocyanates and alkynes has been developed. Heating a mixture of an alkenyl isocyanate and a symmetrical internal alkyne in the presence of [Rh(ethylene)2Cl]2/P(4-OMe-C6H4)3 in toluene delivers substituted indolizinones and quinolizinones. Depending on the substrates, a rare fragmentation of the isocyanate unit can be involved within the cycloaddition process to furnish a vinylogous amide embedded in the indolizinone.     

A general and regioselective synthesis of cyclopentenone derivatives through nickel(0)-mediated [3 + 2] cyclization of alkenyl Fischer carbene complexes and internal alkynes

A broad range of substituted 2-cyclopentenone derivatives 3-6 are synthesized by the nickel(0)-mediated [3 + 2] cyclization reaction of chromium alkenyl(methoxy)carbene complexes 1 and internal alkynes 2. The reaction takes place with complete regioselectivity with both unactivated alkynes and activated alkynes (electron-withdrawing and electron-donating substituted alkynes). Representative cycloadducts containing boron and tin substituents are further demonstrated to be active partners in classical Pd-catalyzed C-C coupling processes to allow the production of 2-aryl- and 2-alkynyl-substituted cyclopentenones 9-13.     

Nickel(0)-mediated [2+2+1] cyclization reaction of chromium carbene complexes and internal alkynes

Alkyl, aryl, and heteroaryl chromium Fischer carbene complexes undergo Ni(0)-mediated [2+2+1] cyclization reaction with internal unactivated and electron-poor internal alkynes to yield highly substituted cyclopentadienes with complete regioselectivity in most cases. The intramolecular version of this cyclization has been accomplished with 1,8-diphenyl-1,7-octadiyne to produce indene derivatives. This three-component [2+2+1] cyclization represents a very uncommon process in the chemistry of Fischer carbene complexes.     

Cationic palladium(II)-catalyzed highly enantioselective [3+2] annulation of 2-acylarylboronic acids with substituted alkynes

A cationic palladium(II)-catalyzed enantioselective tandem [3+2] annulation of 2-acylarylboronic acids with substituted alkynes to yield optically active 1-indenols was developed in high yields and excellent enantioselectivities.     

A [2+2+2]‐Cyclotrimerization Approach to Selectively Substituted Fluorenes and Fluorenols,and Their Conversion to 9,9′‐Spirobifluorenes

Synthesis of selectively substituted fluorenes and fluorenols was achieved by using catalytic [2+2+2]cyclotrimerization. Various starting diynes were reacted with different alkynes in the presence of a catalytic amount of Wilkinson’s catalyst (RhCl(PPh₃)₃) providing the compounds possessing the fluorene scaffold in good isolated yields. A set of four regioselectively substituted fluorenols was converted to the corresponding 9,9′‐spirobifluorenes and their spectral characteristics were measured.     

One pot synthesis of maleimide and hydantoin by Fe(CO)5 catalyzed [2 + 2 + 1] co-cyclization of acetylene, isocyanate and CO

In the presence of a catalytic amount of Fe(CO)(5), terminal acetylenes, isocyanates and CO undergo [2 + 2 + 1] cyclization to form substituted maleimides and hydantoins; when internal alkynes are used, exclusive maleimide formation is observed. While the maleimides can be obtained as the major products, in up to 90% yield, when the reaction is carried out in CO atmosphere, in absence of CO, the hydantoins are formed in up to 87% yield. Formation of maleimides has been shown to occur via the formation of a ferrole intermediate, whereas the hydantoins are proposed to form through successive insertion of isocyanate into the iron-acetylide bond. All compounds were characterized by spectroscopic methods and molecular structures of some compounds were established by single crystal X-ray diffraction method.     

Trimethylsilyl‐Protected Alkynes as Selective Cross‐Coupling Partners in Titanium‐Catalyzed [2+2+1] Pyrrole Synthesis

Trimethylsilyl (TMS)‐protected alkynes served as selective alkyne cross‐coupling partners in titanium‐catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS‐protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido complexes yielded pentasubstituted 2‐TMS‐pyrroles with greater than 90 % selectivity over the other nine possible pyrrole products. The steric and electronic effects of the TMS group were both identified to play key roles in this highly selective pyrrole synthesis. This strategy provides a convenient method to synthesize multisubstituted pyrroles as well as an entry point for further pyrrole diversification through facile modification of the resulting 2‐silyl pyrrole products, as demonstrated through a short formal synthesis of the marine natural product lamellarin R.     

Nickel-catalyzed [4+2] cycloaddition for highly substituted arenes

Nickel(0) catalyzed [4+2] cycloaddition of electron-deficient dienes to alkynes and subsequent aromatization gave highly substituted arenes. This formal inverse electron-demand Diels-Alder cycloaddition is attributed to the formation of a seven-membered nickelacycle from a diene and an alkyne.     

Nickel‐Catalyzed Facile [2+2+2] Cyclotrimerization of Unactivated Internal Alkynes to Polysubstituted Benzenes

A catalytic [2+2+2] cyclotrimerization of unactivated internal alkynes providing cyclotrimerization products in excellent yields with high regioselectivity is described. The transformation is accomplished by using a simple catalytic mixture comprising Ni(acac)₂, an imidazolium salt and a Grignard reagent at room temperature or 60 °C for 20 min or 1 h.     

Visible‐Light‐Induced [4+2] Annulation of Thiophenes and Alkynes to Construct Benzene Rings

The [4+2] annulation represents an elegant and versatile synthetic protocol for the construction of benzene rings. Herein, a strategy for visible‐light induced [4+2] annulation of thiophenes and alkynes, to afford benzene rings, is presented. Under simple and mild reaction conditions, the ready availability and structural diversity of thiophenes and alkynes permit the facile synthesis of several substituted aromatic rings. Valuable drugs and amino acids are also well tolerated. Moreover, DFT calculations explain the high regioselectivity of the reaction.     

[5+2] Cycloaddition of 2‐(2‐Aminoethyl)oxiranes with Alkynes via Epoxide Ring‐Opening: A Facile Access to Azepines

A new FeCl₃ and BF₃?OEt₂ co‐catalyzed tandem hetero‐[5+2] cycloaddition of 2‐(2‐aminoethyl)oxiranes with a wide range of alkynes, including terminal alkynes and alkyl‐substituted internal alkynes is presented. This is the first example of rapid and facile production of diverse 2,3‐dihydro‐1H‐azepines through a sequence of epoxide ring‐opening, annulation, and dehydroxylation with broad substrate scope and exquisite selectivity control.