A mechanistic study of the utilization of arachno-diruthenaborane [(Cp*RuCO)2B2H6] as an active alkyne-cyclotrimerization catalyst

The reaction of nido-[1,2-(Cp*RuH)(2)B(3)H(7)] (1a, Cp*=η(5)-C(5)Me(5)) with [Mo(CO)(3)(CH(3)CN)(3)] under mild conditions yields the new metallaborane arachno-[(Cp*RuCO)(2)B(2)H(6)] (2). Compound 2 catalyzes the cyclotrimerization of a variety of internal- and terminal alkynes to yield mixtures of 1,3,5- and 1,2,4-substituted benzenes. The reactivities of nido-1a and arachno-2 with alkynes demonstrates that a change in geometry from nido to arachno drives a change in the reaction from alkyne-insertion to catalytic cyclotrimerization, respectively. Density functional calculations have been used to evaluate the reaction pathways of the cyclotrimerization of alkynes catalyzed by compound 2. The reaction involves the formation of a ruthenacyclic intermediate and the subsequent alkyne-insertion step is initiated by a [2+2] cycloaddition between this intermediate and an alkyne. The experimental and quantum-chemical results also show that the stability of the metallacyclic intermediate is strongly dependent on the nature of the substituents that are present on the alkyne.     

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.     

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.     

Synthesis of the pyridine core of cyclothiazomycin

A highly convergent synthesis of the pyridine core of the thiopeptide antibiotic cyclothiazomycin has been developed based on a [2+2+2] cyclotrimerization key step. The regioselective assembly of the heterocyclic center of this important class of antibiotics takes advantage of a temporary silicon tether and the ruthenium-catalyzed cyclotrimerization reaction of a diyne and an electron-poor thiazole nitrile.     

A cyclotrimerization route to cannabinoids

Three members of the cannabinoid class, cannabinol, cannabinol methyl ether, and cannabinodiol, were synthesized using a microwave-mediated [2 + 2 + 2] cyclotrimerization reaction as the key step. This approach provides a high level of synthetic flexibility allowing for the facile synthesis of cannabinoid analogues.     

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.     

Total syntheses of the marine illudalanes alcyopterosin I, L, M, N, and C

The combination of a modular assembly of enantiopure triynes and a powerful rhodium-catalyzed [2 + 2 + 2] alkyne cyclotrimerization reaction opens new and efficient entries to a set of alcyopterosins, including the first total synthesis of the alcyopterosins L, M, and C.     

[1+1+1] Cyclotrimerization for the Synthesis of Cyclopropanes

The synthesis of small rings by functionalization of C(sp³)?H bonds remains a great challenge. We report for the first time a copper‐catalyzed [1+1+1] cyclotrimerization of acetophenone derivatives under mild reaction conditions. The reaction has a broad scope for the stereoselective synthesis of cyclopropanes by trimerization of acetophenone. The developed transformation is based on an extraordinary copper‐catalyzed cascade process that allows saturated carbocycles to be obtained for the first time by cyclotrimerization through functionalization of C(sp³)?H bonds. The cascade of sixfold C(sp³)?H bond functionalization allows the synthesis of cyclopropanes in a highly stereoselective approach.     

Synthesis of New Phosphahelicene Scaffolds and Development of Gold(I)‐Catalyzed Enantioselective Allenene Cyclizations

This paper reports on the development of an efficient synthesis of enantiopure phospha[6]helicenes through a [2+2+2] alkyne cyclotrimerization reaction. The corresponding gold complexes proved to be highly efficient both in terms of catalytic activity and enantioselectivity in [2+2] and [4+2] cycloaddition reactions. Furthermore, in the presence of an external nucleophile, such as water or alcohols, the tandem cyclization/addition reactions take place in high yields and excellent diastereo‐ and enantioselectivities.     

Transition metal-mediated intramolecular [2+2+2] cycloisomerizations of cyclic triynes and enediynes

[reaction: see text] Nitrogen-containing 15-membered triacetylenic macrocycles known as 1,6,11-tris(arylsulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-triynes (1) and enediynic macrocycles called 1,6,11-tris(arylsulfonyl)-1,6,11-triazacyclopentadeca-3-ene-8,13-diynes (4 and 5) were satisfactorily prepared. [2+2+2] cycloisomerization processes catalyzed by transition metals were tested in the above-mentioned macrocycles. Readily available and familiar cyclotrimerization precatalysts were examined for efficiency. Among them, the RhCl(CO)(PPh(3))(2) complex was found to catalyze the cycloisomerization reaction giving the desired cycloadducts in high yields.     

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.     

Cyclotrimerization reactions of arynes and strained cycloalkynes

The use of arynes and related species as substrates in metal-catalyzed cycloaddition reactions leads to structurally interesting products. Palladium-catalyzed cyclotrimerization of arynes provides a new method for the synthesis of polycyclic aromatic hydrocarbons. For instance, the chemoselective formal [2 + 2 + 2] cocycloaddition of 2,3-triphenylynes with alkynes affords extended triphenylenes, which are good candidates to behave as liquid crystals. Cotrimerization of benzyne and electron-deficient alkenes selectively affords dihydrophenanthrenes or ortho-olefinated biaryls depending on the catalytic system employed. The use of 2,2'-bis(diphenylphosphino)-1,1'-binophythyl (BINAP)-based palladium(0) catalysts in the cocyclotrimerization of 7-methoxynaphthalyne and dimethyl acetylenedicarboxylate affords an enantiomerically enriched tetrasubstituted pentahelicene, the first example of a metal-catalyzed enantioselective reaction involving arynes. Strained cyclic alkynes can also participate in the palladium-catalyzed cyclotrimerization reactions, which again lead to structurally interesting products.     

钯催化的炔烃芳构化反应研究

综述了钯络合物催化的炔烃环三聚芳构化反应的历史沿革及最新研究进展,并结合该研究小组的工作,重点阐述了钯催化炔烃 [ 2+2+2 ] 环三聚芳构化、双炔烃、共轭烯炔 [ 4+2 ] 芳构化反应。同时对反应的几种典型催化体系和反应机理,以及该领域的一些前沿热点也作了综述。     

Design,Synthesis and Late-Stage Modification of Indane-Based Peptides via [2+2+2] Cyclotrimerization

Here, we prepared several dipeptides containing 2-aminoindane-2-carboxylic acid (Aic) and carried out further synthetic transformations. Synthesis and purification of modified peptides by using [2+2+2] cyclotrimerization is a challenging task. We are able to modify the unusual amino acids and peptide derivatives by late-stage incorporation of benzylhalo functionality. To incorporate benzylhalo moiety we used [2+2+2] cyclotrimerization in the presence of Mo(CO)₆. These halo derivatives are potential substrates for further modification by Sonogashira reaction, Suzuki–Miyaura cross-coupling, sultine formation, and the Diels–Alder reaction sequence.     

Fine‐Tuning the Reactivity and Stability by Systematic Ligand Variations in CpCoI Complexes as Catalysts for [2+2+2] Cycloaddition Reactions

CpCo^I‐olefin‐phosphite and CpCo^I‐bisphosphite complexes were systematically prepared and their reactivity in [2+2+2] cycloaddition reactions compared with highly active [CpCo(H₂C?CHSiMe₃)₂] ( 1 ). Whereas 1 is an excellent precursor for the synthesis of [CpCo(olefin)(phosphite)] complexes ( 2 a – f ), [CpCo(phosphite)₂] complexes ( 3 a – e ) were prepared photochemically from [CpCo(cod)]. The complexes were evaluated in the cyclotrimerization reaction of diynes with nitriles yielding pyridines. For [CpCo(olefin)(phosphite)], as well as some of the [CpCo(phosphite)₂] complexes, reaction temperatures as low as 50 °C were sufficient to perform the cycloaddition reaction. A direct comparison showed that the order of reactivity for the complex ligands was olefin₂>olefin/phosphite>phosphites₂. The complexes with mixed ligands favorably combine reactivity and stability. Calculations on the ligand dissociation from [CpCo(olefin)(phosphite)] proved that the phosphite is dissociating before the olefin. [CpCo(H₂C?CHSiMe₃){P(OPh)₃}] ( 2 a ) was investigated for the co‐cyclization of diynes and nitriles and found to be an efficient catalyst at rather mild temperatures.     

Synthesis of indanones via solid-supported [2+2+2] cyclotrimerization

A new facile approach toward natural and unnatural indanones has been developed, featuring a solid-supported [2+2+2] cyclotrimerization as the key step. This strategy has been applied to the chemo- and regioselective assembly of indanone arrays and to the total synthesis of a recently isolated indanone marine natural product.     

Reactive N-protonated isocyanate species stabilized by bis(μ-hydroxo)divanadium(IV)-substituted polyoxometalate

O- or N-protonated? The bis(μ-hydroxo)divanadium(IV)-substituted γ-Keggin-type polyoxometalate (see picture, left) (TBA)(4)[γ-SiV(IV)(2)W(10)O(36)(μ-OH)(4)] (TBA = tetra(n-butyl)ammonium) was synthesized and characterized by X-ray crystallography. Its reaction with phenyl isocyanate gave (TBA)(4)[γ-SiV(IV)(2)W(10)O(38)(μ-OH)(2)(PhNHCO)(2)], which contains two N-protonated phenyl isocyanate species and catalyzes the cyclotrimerization of phenyl isocyanate.     

The fascinating construction of pyridine ring systems by transition metal-catalysed [2 + 2 + 2] cycloaddition reactions

Cycloaddition reactions compose one of the most important classes of reactions when it comes to the simultaneous formation of several bonds in one reaction step. The de novo construction of carbocyclic aromatic systems from acetylenes was also found as an excellent possibility for the assembly of heteroaromatic systems. The transition metal-catalysed [2 + 2 + 2] cycloaddition reaction constitutes a fascinating tool for the synthesis of pyridines from nitriles and the most recent developments demonstrate the ability to control the substitution pattern as well as the possibility of introducing chirality by the use of achiral substrates and a chiral catalyst under mild conditions. In this tutorial review we are focusing on the de novo construction of pyridine ring systems by the transition metal-catalysed [2 + 2 + 2] cycloaddition reaction. After surveying the mechanistic features and intermediates of the reaction depending on the different metal complexes used, we depict the preparation of achiral pyridine derivatives. The last section describes the advances in the synthesis of chiral pyridines and biaryls using the cyclotrimerization method. The various possibilities of introducing chirality by catalytic means are presented and illustrated by instructive examples. This review will be of interest for people active in: Organic Chemistry, Organometallic Chemistry, Transition Metal Chemistry, Stereoselective Synthesis, Heterocyclic Chemistry.     

Acetylene cyclotrimerization catalyzed by TiO2 and VO2 in the gas phase: a DFT study

Density functional theory (DFT) calculations have been used to investigate acetylene cyclotrimerization catalyzed by titanium and vanadium dioxides. The calculated results illustrate that the overall process is highly favorable at room temperature from both thermodynamic and kinetic points of view. The mechanism of C2H2 cyclotrimerization over MO2 (M = Ti, V) can be understood as four steps: (1) a four-membered ring (-O-M-C=C-) formation that coordinates and activates the first C2H2 molecule; (2) the second C2H2 insertion into the M-C bond to form a six-membered ring (-O-M-C=C-C=C-); (3) the third C2H2 insertion into the M-C bond to form an eight-membered ring (-O-M-C=C-C=C-C=C-); and (4) contraction of the eight-membered ring and benzene formation and desorption. All of the reaction steps are overall barrierless with respect to the separated reactants (MO2C2xH2x + C2H2, x = 0, 1, 2). This theoretical study predicts that the M=O double bond in MO2 is very catalytic toward the C2H2 cyclotrimerization. The metal center in this study can be considered always in the same +4 oxidation state (Ti4+ and V4+). In contrast, two-electron cycling of the metal center is present in the documented mechanism for the C2H2 cyclotrimerization. The C2H2 cyclotrimerization over the Ti atom and TiO molecule is also studied, and the documented mechanism applies in this case. The new mechanism is suggested to apply to reactions using titanium and vanadium oxides as catalysts.     

Target cum flexibility: synthesis of C(3′)-spiroannulated nucleosides

We report a simple strategy for the synthesis of a collection of C(3′)-spirodihydroisobenzo-furannulated nucleosides featuring a [2+2+2]-cyclotrimerization as the key reaction. The cyclotrimerization reactions are facile with the unprotected nucleosides having a diyne unit. When both alkynes of the diyne are terminal, the regioselectivity is poor. However, when one of the terminal alkynes is additionally substituted, the cyclotrimerizations are highly diastereoselective. Since the key bicycloannulation is the final step, this strategy provides flexibility in terms of the alkynes and is thus amenable for the synthesis of a focussed small molecule library.