Cyclization Of Enynes Research Articles

Palladium-Catalyzed Intramolecular Alder-Ene Type Cycloisomerization Reactions.

An overview of the recent literature on palladium-catalyzed intramolecular Alder-ene (IMAE) reaction of a variety of 1,n-unsaturated systems is presented. The reaction which was first reported by Trost and Lautens provided an efficient alternative to the thermal or Lewis acid catalyzed cycloisomerizations involving ene-type reaction. The IMAE cyclization of enynes and dienes has emerged as an important area and found significant applications in building up of complex molecular architectures and in the synthesis of several bioactive natural products. Since highly impactful reviews on this subject have covered the literature till 2015, this article focuses on summarizing the works subsequent to 2015.

Highly Strained Unsaturated Carbocycles

Highly strained unsaturated carbocyclic rings are high‐energy compounds which are attracting increasing interest – not just for their peculiar structural and reactivity features – but also as modern chemical tools for bioorthogonal and in vivo chemistry, especially via inverse‐electron demand Diels–Alder (iEDDA) and strain‐promoted azide‐alkyne cycloaddition (SPAAC) reactions. This mini‐review covers two main classes of compounds: 3 to 10 membered‐ring cycloalkynes and trans‐cycloalkenes, including some examples of cyclic enynes, dienes and bridgehead alkenes. Their molecular properties, synthesis and reactivity are presented and discussed, with an emphasis on their functionalization and reactivity.

Cover Picture: Carbon–Carbon Bond Formation via Catalytically Generated Aminocarbene Complexes: Rhodium‐Catalyzed Hydroaminative Cyclization of Enynes with Secondary Amines (Angew. Chem. Int. Ed. 29/2020)

Cover Picture: Carbon–Carbon Bond Formation via Catalytically Generated Aminocarbene Complexes: Rhodium‐Catalyzed Hydroaminative Cyclization of Enynes with Secondary Amines (Angew. Chem. Int. Ed. 29/2020)

Carbon–Carbon Bond Formation via Catalytically Generated Aminocarbene Complexes: Rhodium‐Catalyzed Hydroaminative Cyclization of Enynes with Secondary Amines

AbstractWe report a hydroaminative cyclization of enynes using phosphine‐quinolinolato rhodium catalysts. The hydroaminative cyclization of 2‐vinylphenylacetylene derivatives with secondary amines gives 2‐aminoindenes in good yields. The reaction is considered to proceed through carbon–carbon bond formation on a catalytically generated aminocarbene ligand.

Carbon-Carbon Bond Formation via Catalytically Generated Aminocarbene Complexes: Rhodium-Catalyzed Hydroaminative Cyclization of Enynes with Secondary Amines.

We report a hydroaminative cyclization of enynes using phosphine-quinolinolato rhodium catalysts. The hydroaminative cyclization of 2-vinylphenylacetylene derivatives with secondary amines gives 2-aminoindenes in good yields. The reaction is considered to proceed through carbon-carbon bond formation on a catalytically generated aminocarbene ligand.

A Stiboranyl Platinum Triflate Complex as an Electrophilic Catalyst

With the view of developing electrophilic late-transition-metal catalysts, we have now synthesized [(o-(Ph2P)C6H4)2Sb(OTf)2]Pt(OTf) (2) and [(o-(iPr2P)C6H4)2Sb(OTf)2]Pt(OTf) (4) by treatment of the corresponding trichlorides ([(o-(R2P)C6H4)2SbCl2]PtCl (R = Ph, iPr)) with 3 equiv of AgOTf. The crystal structures of 2 and 4 confirmed that the chloride ligands have been fully substituted by more labile triflate ligands. Despite structural similarities in the dinuclear cores of 2 and 4, only 2 acts as a potent carbophilic catalyst in enyne cyclization reactions. The high activity of 2 is also reflected by its ability to promote the addition of pyrrole and thiophene derivatives to alkynes. Structural and computational analyses suggest that the superior reactivity of 2 results from both favorable steric and electronic effects. Finally, a comparison of 2 with the previously reported self-activating catalyst [(o-(Ph2P)C6H4)2Sb(OTf)2]PtCl underscores the benefits of triflate for chloride substitution.

Cobalt-Catalyzed Enantioselective Hydroarylation of 1,6-Enynes.

An asymmetric hydroarylative cyclization of enynes involving a C-H bond cleavage is reported. The cobalt-catalyzed cascade generates three new bonds in an atom-economical fashion. The products were obtained in excellent yields and excellent enantioselectivities as single diastereo- and regioisomers. Preliminary mechanistic studies indicate that the reaction shows no intermolecular C-H crossover. This work highlights the potential of cobalt catalysis in C-H bond functionalization and enantioselective domino reactivity.

Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones

The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.01,5]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.01,5]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio- and enantioselectivities (92–99% ee).

Visible-Light Mediated Hydrosilylative and Hydrophosphorylative Cyclizations of Enynes and Dienes.

Described herein is a visible-light mediated intermolecular radical cyclization approach to access heterocycles. Heteroatom radicals, such as silicon and phosphorus atom radicals, were generated via direct hydrogen atom abstraction by the photoexcited catalyst species with hydro-silanes and phosphine oxides. The radical addition/cyclization/HAT (hydrogen atom transfer) reaction sequences of 1,6-enynes and 1,6-dienes were highly efficient delivering the desired heterocycles in good yields.

Synthesis and Rh-catalyzed reductive cyclization of 1,6-enynes and 1,6-diynes containing alkynylboronate termini

Ir-catalyzed dehydrogenative borylation of terminal alkynes (DHBTA) has been used to borylate the C(sp)-H bond in a series of 1,6-enynes and 1,6-diynes. Ir catalysts based on the diarylamido/bis(phosphine) PNP ligands proved to be capable of performing DHBTA on these substrates. The alkynylboronate products were then explored as substrates in reductive cyclization reactions designed to yield five-membered carbocycles and heterocycles with preservation of the carbon-boron bond. The reductive cyclization of enynes with H2 was carried out using cationic Rh catalysts (after the work of Krische et al.) supported by bidentate phosphine ligands, of which BINAP proved to be the generally best performing. Reductive cyclization of borylated enynes typically resulted in mixtures of isomeric products. Attempts to optimize the reductive cyclization of borylated 1,6-enynes to yield a single product were not successful; in addition, the distribution of products in these reactions was poorly reproducible. On the other hand, reductive cyclization of 1,6-diynes with the same Rh catalysts was better behaved, allowing for selectivity and reproducibility. In particular, alkynylboronate derivatives of bis(propargyl)amine underwent smooth reductive cyclization to 3,4-substituted pyrroles. The influence of substituents and conditions on the product distribution was explored and representative reactions utilizing new borylated heterocycles in Suzuki coupling reactions were carried out.

Gold(i)-catalyzed tandem cyclization of cyclopropylidene-tethered propargylic alcohols: an approach to functionalized naphtho[2,3-c]pyrans.

An unprecedented gold(i)-catalyzed cyclization of cyclopropylidene-tethered propargylic alcohols via a 6-endo-dig enyne cyclization followed by a ring-opening of cyclopropane and nucleophilic closure reaction to construct naphtho[2,3-c]pyrans was developed. This transformation represents a highly efficient method for the synthesis of polycyclic compounds in one-pot, and two new rings are formed in an atom economic manner.

Ni-Catalyzed Cyclization of Enynes and Alkynylboronates: Atom-Economical Synthesis of Boryl-1,4-dienes.

We report a novel atom-economical Ni-catalyzed cyclization reaction of enynes with alkynylboronates. The reaction employs a non-expensive Ni salt, a phosphine-based ligand and easy-handling alkynylboronates as boron-carbon source. The reaction provides complex fused-bicyclic compounds containing borylated 1,4-cyclohexadienes in high yields in short reaction times, involving the formation of two C-C bonds in one step. A reasonable reaction mechanism is proposed based on mechanistic experimental results.

Gold-Catalyzed Enantioselective Cyclizations of Enynes through Remote Enantioinduction

Gold-Catalyzed Enantioselective Cyclizations of Enynes through Remote Enantioinduction

Direct Access to Trifluoromethyl-Substituted Carbamates from Carbon Dioxide via Copper-Catalyzed Cascade Cyclization of Enynes.

A copper-catalyzed cascade cyclization of enynes with Togni's reagent, carbon dioxide, and amines has been successfully developed. The reaction provides a direct and efficient route to a range of trifluoromethyl-substituted carbamates, which are difficult to access using existing methods. Mild reaction conditions, good functional tolerance, and wide substrate scope are the feactures of the protocol.

Atom-Economical Ni-Catalyzed Diborylative Cyclization of Enynes: Preparation of Unsymmetrical Diboronates.

We report a Ni-catalyzed diborylative cyclization of enynes that affords carbo- and heterocycles containing both alkyl- and alkenylboronates. The reaction is fully atom-economical, shows a broad scope, and employs a powerful and inexpensive catalytic Ni-based system. The reaction mechanism seems to involve activation of the enyne by Ni(0) through oxidative cyclometalation of the enyne prior to diboron reagent activation. An unprecedented dinuclear bis(organometallic) Ni(I) intermediate complex was isolated.

Synthesis of Diiodinated All-Carbon 3,3'-Diphenyl-1,1'-spirobiindene Derivatives via Cascade Enyne Cyclization and Electrophilic Aromatic Substitution.

A synthetic method for the construction of diiodinated all-carbon spirobiindene derivatives has been developed from the reaction of propargyl alcohol-tethered alkylidenecyclopropanes with iodine. The reaction proceeded through an iodination-initiated cascade intramolecular enyne cyclization and electrophilic aromatic substitution reaction process in 1,2-dichloroethane upon heating, giving desired spirocyclic products in moderate to excellent yields. Further transformation of the obtained products has also been presented.

Cover Picture: Rhodium(I)‐Catalyzed Enantioselective Cyclization of Enynes by Intramolecular Cleavage of the Rh−C Bond by a Tethered Hydroxy Group (Angew. Chem. Int. Ed. 26/2019)

Cover Picture: Rhodium(I)‐Catalyzed Enantioselective Cyclization of Enynes by Intramolecular Cleavage of the Rh−C Bond by a Tethered Hydroxy Group (Angew. Chem. Int. Ed. 26/2019)

Visible-Light-Driven Chlorotrifluoromethylative and Chlorotrichloromethylative Cyclizations of Enynes.

Described herein is a visible-light-driven chlorotrifluoromethylative and chlorotrichloromethylative cyclization reaction to synthesize chlorotrifluoromethylated and chlorotrichloromethylated cyclic compounds. Visible-light photochemistry was utilized to generate trifluoromethyl and trichloromethyl radicals and trigger radical addition/cyclization/chlorination sequences. The use of terminal alkene-derived enynes enables the regioselective and stereoselective synthesis of chlorotrifluoromethylated and chlorotrichloromethylated pyrrolidines, piperidines, and cyclopentanes.

Rhodium(I)‐Catalyzed Enantioselective Cyclization of Enynes by Intramolecular Cleavage of the Rh−C Bond by a Tethered Hydroxy Group

AbstractRhodium(I)‐catalyzed enantioselective intramolecular cyclization of enynes having a hydroxy group in the tether was investigated, and various cyclic compounds possessing a chiral quaternary carbon center were obtained in high yields with high ees. In this cyclization, a Rh−C(sp2) bond in the rhodacyclopentene intermediate, which was formed by enantioselective oxidative cycloaddition of enynes to a chiral rhodium(I) complex, was intramolecularly cleaved by σ‐bond metathesis of a tethered O−H bond in the substrate. Furthermore, it was found that the cyclic compounds were obtained with high ees even when the starting materials having a racemic secondary alcohol moiety were used in this reaction.

Rhodium(I)-Catalyzed Enantioselective Cyclization of Enynes by Intramolecular Cleavage of the Rh-C Bond by a Tethered Hydroxy Group.

Rhodium(I)-catalyzed enantioselective intramolecular cyclization of enynes having a hydroxy group in the tether was investigated, and various cyclic compounds possessing a chiral quaternary carbon center were obtained in high yields with high ees. In this cyclization, a Rh-C(sp2 ) bond in the rhodacyclopentene intermediate, which was formed by enantioselective oxidative cycloaddition of enynes to a chiral rhodium(I) complex, was intramolecularly cleaved by σ-bond metathesis of a tethered O-H bond in the substrate. Furthermore, it was found that the cyclic compounds were obtained with high ees even when the starting materials having a racemic secondary alcohol moiety were used in this reaction.