Microwave-mediated nickel-catalyzed cyclotrimerization reactions: total synthesis of illudinine

Rapid and efficient [2 + 2 + 2] cyclotrimerization reactions were discovered through the application of microwave irradiation in conjunction with a Ni(CO)(2)(PPh(3))(2) catalyst. This enables the facile construction of highly substituted indane, isoindoline, and tetraline core structures. The developed microwave-mediated Ni-catalyzed cyclotrimerization reaction was employed as the key step in a concise synthesis of the isoquinoline natural product illudinine. This represents the first example of a Ni-catalyzed cyclotrimerization reaction in total synthesis.     

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。     

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.     

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.     

Cobalt-catalyzed cyclotrimerization of diynes with norbornenes in one efficient step

An efficient cobalt-catalyzed [2+2+2] cyclotrimerization of diynes and norbornene is described. Treatment of diyne with norbornene in the presence of CoI₂(PPh₃)₂ and zinc powder in 1,2-dichloroethane at 80 °C for 12 h afforded [2+2+2] cyclotrimerization adduct exclusively in good yields. These cobalt-catalyzed results are in contrast to the ruthenium-catalyzed reaction of diyne with norbornene reported previously.     

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.     

Mechanisms of the thermal cyclotrimerizations of fluoro- and chloroacetylenes: density functional theory investigation and intermediate trapping experiments

Theoretical studies of the mechanisms of the thermal cyclotrimerization of fluoro- and chloroacetylenes, which were reported by Viehe and Ballester, respectively, were conducted with the aid of density functional theory calculations of the (U)B3LYP functional, indicating that the thermal cyclotrimerizations of fluoro- and chloroacetylenes involve tandem processes of regioselectively stepwise [2+2] and stepwise [4+2] cycloadditions. These tandem processes generate 1,2,6-trihalo-Dewar benzenes and 1,2,4-trihalo-Dewar benzenes, which then isomerize to the corresponding benzenes when heated. The rate-determining step of the cyclotrimerizations of haloacetylenes is the dimerization step involving open-shell singlet diradical transition states and intermediates. The substituent effects in the thermal cyclotrimerization of haloacetylenes have been rationalized using frontier molecular orbital theory. The higher reactivity of fluoroacetylenes compared to that of chloroacetylenes is due to the fact that fluoroacetylenes have lower singlet-triplet gaps than chloroacetylenes and more easily undergo dimerization and cyclotrimerization. In this report, additional experiments were performed to verify the theoretical prediction about the cyclotrimerization of chloroacetylene and to trap the proposed 1,4-dichlorocyclobutadiene intermediate. Experiments revealed that the thermal reaction of phenylchloroacetylene at 110 °C gave 1,2,3-triphenyltrichlorobenzene and 1,2,4-triphenyltrichlorobenzene together with a tetramer, cis-1,2,5,6-tetrachloro-3,4,7,8-tetraphenyltricyclo[4.2.0.0(2,5)]octa-3,7-diene. The proposed 1,4-diphenyldichlorocyclobutadiene intermediate in the thermal cyclotrimerization of phenylchloroacetylene was successfully trapped using dienophiles of maleic anhydride and dimethyl acetylenedicarboxylate.     

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.     

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.     

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.     

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.     

New efficient construction of the ABC core of the taxoids via a sequence of consecutive cobalt(I)-mediated [2 + 2 + 2] and [4 + 2] cyclizations

[reaction: see text] A new and efficient sequence of two consecutive cyclizations, a cobalt(I)-mediated [2 + 2 + 2] cyclotrimerization and a Diels-Alder reaction, is proposed to allow the formation of the ABC core of the taxoids in 65% overall yield, starting from an acyclic polyunsaturated precursor.     

Ru(II)-catalyzed chemo- and regioselective cyclotrimerization of three unsymmetrical alkynes through boron temporary tether. One-pot four-component coupling via cyclotrimerization/Suzuki-Miyaura coupling

The Ru(II)-catalyzed [2+2+2] cyclotrimerization of alkynylboronates, propargyl alcohol, and terminal alkynes proceeded chemo- and regioselectively to give rise to arylboronates, which were subjected to Suzuki-Miyaura cross-coupling with aryliodides to afford highly substituted biaryls in 53-76% yields.     

Synthesis of anthracene and azaanthracene fluorophores via [2+2+2] cyclotrimerization reactions

A highly convergent [2+2+2] cyclotrimerization approach to anthracenes and 2-azaanthracenes has been developed. It allows for the facile introduction of the anthracene moiety on alkyne and nitrile bearing molecules and the rapid construction of compound arrays. This is showcased in the assembly of a collection of fluorophores and their photochemical evaluation.     

Metal‐Free [2+2+2] Cycloaddition of Ynamides and Nitriles: Mild and Regioselective Synthesis of Fully Substituted Pyridines

A metal‐free trimolecular [2+2+2] cycloaddition of internal ynamides and nitriles for de novo synthesis of fully substituted pyridines is disclosed. With the versatile Brønsted acid catalyst HNTf₂, the mild intermolecular cyclotrimerization process proceeds with complementary chemoselectivity and excellent regioselectivity.     

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.     

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.     

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.     

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.     

Lanthanide triflate-catalyzed preparation of beta,beta-difluorohomopropargyl alcohols in aqueous media. Application to the synthesis of 4,4-difluoroisochromans

An indium-mediated Barbier-type reaction of difluoropropargyl bromide with several aldehydes in aqueous media was enhanced by a catalytic amount of a lanthanide triflate (5 mol %). The reaction gave the corresponding beta,beta-difluorohomopropargyl alcohols with high regioselectivity. The [2 + 2 + 2] alkyne cyclotrimerization of beta,beta-difluorohomopropargyl alcohols with monosubstituted acetylenes produced 4,4-difluoroisochromans in good yields with moderate regioselectivity.