Allenic Esters Research Articles

Palladium-Catalyzed [2+3] Cycloaddition/Cross-Coupling Reaction: Z/E and Diastereoselective Synthesis of Dendralene-Functionalized Dihydrofurans.

Herein, we describe a Pd-catalyzed [2+3] cycloaddition/cross-coupling reaction of allenyl acetates for the Z/E selective and diastereoselective synthesis of dendralene-functionalized dihydrofurans. Remarkably, mechanistic studies show the formation of an epoxide from a carbonyl bond via cycloaddition, which is practically and mechanistically significant for the construction of other bioactive heterocyclic epoxides. This research also revealed the utility and potential of allenic esters as C2 synthons and 1,2-biselectrophiles in cycloaddition reactions.

Visible‐Light‐Assisted Gold‐Catalyzed Fluoroarylation of Allenoates

AbstractA strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β‐fluoroalkyl‐containing cinnamate derivatives. The reaction proceeds through visible‐light‐promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio‐ and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.

Visible‐Light‐Assisted Gold‐Catalyzed Fluoroarylation of Allenoates

A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.

Substrate-controlled, PBu3-catalyzed annulation of phenacylmalononitriles with allenoates enables tunable access to cyclopentenes.

Divergence in the PBu3-catalyzed [3+2] annulation of phenacylmalononitriles with allenoates, controlled by the γ-substitution on allenoates, offers a tunable synthesis of multifunctionalized cyclopentene carboxamides and cyclopentenols. An unprecedented formation of cyclopentene carboxamide was observed when allenic esters bearing a substitution at the γ-position were employed, while unsubstituted allenoates produced cyclopentenols. The former reaction likely involves a Michael/aldol/nucleophilic cyclization sequence in a domino manner.

Phosphine‐Catalyzed β‐Selective Conjugate Addition of α‐Fluoro‐β‐ketoamides to Allenic Esters

A Strategy for the β‐selective conjugate addition of α‐fluoro‐β‐ketoamides to allenic esters has been developed via phosphine catalysis. This protocol exhibits a broad substrate scope, and a wide range of compounds bearing fluorinated quaternary carbon center was obtained in good to excellent yields. This protocol allows the use of γ‐substituted allenic esters to furnish the products with exclusive β‐selectivity.

Phosphane‐Catalyzed [3+2] Annulation of Allenoates with 3‐Nitro‐2H‐chromenes: Synthesis of Tetrahydrocyclopenta[c]chromenes

The synthesis of carbocyclic‐fused chromene derivatives based on allene chemistry is described. The phosphane‐catalyzed [3+2] annulation reactions of allenic esters with 3‐nitrochromenes have been established affording 3a‐nitro‐tetrahydrocyclopenta[c]chromenes in good yields (up to 87 %) with high stereo‐ and regioselectivity. Quantum chemical calculations, carried out at the DFT level of theory, were in agreement with the observed selectivity. The trichlorosilane‐mediated reduction of the 3a‐nitro‐tetrahydrocyclopenta[c]chromenes into the corresponding amines is also reported.

Thioallenoates in catalytic enantioselective [2+2]-cycloadditions with unactivated alkenes

The application of thioallenoates to catalytic enantioselective [2+2]-cycloadditions with unactivated alkenes is reported. In many cases, the thioallenoates examined exhibit superior reactivity and selectivity compared to the allenic esters generally used in these cycloadditions.

Regioselectivity Switch in Palladium-Catalyzed Allenylic Cycloadditions of Allenic Esters: [4+1] or [4+3] Cycloaddition/Cross-Coupling.

The first Pd-catalyzed asymmetric allenylic [4+1] cycloaddition was successfully developed. Alternatively, tuning the Pd catalyst switched the reactivity toward an unprecedented [4+3] cycloaddition/cross-coupling. Ligands play a vital role in controlling the reaction pathway, allowing highly selective access to different products from identical substrates. Biological evaluation of the obtained compounds led to the discovery of new antitumor targets. A possible mechanism is proposed, suggesting two interesting catalytic cycles for the cycloaddition with palladium-butadienyls. This study also demonstrated the potential and utility of allenic esters as 1,4-biselectrophiles and C4 synthons for participating in cycloaddition reactions.

Regioselectivity Switch in Palladium‐Catalyzed Allenylic Cycloadditions of Allenic Esters: [4+1] or [4+3] Cycloaddition/Cross‐Coupling

AbstractThe first Pd‐catalyzed asymmetric allenylic [4+1] cycloaddition was successfully developed. Alternatively, tuning the Pd catalyst switched the reactivity toward an unprecedented [4+3] cycloaddition/cross‐coupling. Ligands play a vital role in controlling the reaction pathway, allowing highly selective access to different products from identical substrates. Biological evaluation of the obtained compounds led to the discovery of new antitumor targets. A possible mechanism is proposed, suggesting two interesting catalytic cycles for the cycloaddition with palladium‐butadienyls. This study also demonstrated the potential and utility of allenic esters as 1,4‐biselectrophiles and C4 synthons for participating in cycloaddition reactions.

Additive-free regio- and diastereoselective construction of fully-substituted isoxazolidines employing diazo compounds

An efficient additive-free three-component access to densely functionalized isoxazolidines using diazo compounds, nitrosoarene, and allenic esters has been uncovered.

Phosphine-catalyzed regiospecific (3 + 2) cyclization of 3-nitroindoles with allene esters.

A phosphine-catalyzed regiospecific (3 + 2) cyclization of 3-nitroindoles with allene esters has been established, which constructed indole-fused five-membered rings in good yields (up to 86%). This reaction serves as a powerful method for the construction of indole-fused five-membered rings. In addition, this reaction provides a useful strategy toward settling the challenge of utilizing other 1,3-dipoles or 1,3-dipole surrogates to perform (3 + 2) cyclizations with 3-nitroindoles in different catalytic modes, which will enrich the chemistry of nitroindoles and catalytic asymmetric dearomatization cyclizations.

Palladium-catalyzed [3+2] annulation of allenyl carbinol acetates with C,N-cyclic azomethine imines.

In this paper, a palladium-catalyzed [3+2] annulation of allenyl carbinol acetates with azomethine imines has successfully been developed under mild reaction conditions, affording biologically interesting tetrahydropyrazoloisoquinoline derivatives in high to excellent yields and with excellent stereoselectivity. The reaction follows a tandem [3+2] cycloaddition/allylation/elimination of AcOH pathway. Allenyl carbinol acetates also reacted well with in situ generated azomethine imine under cocatalysis of Ag(i)/Pd(0) catalysts in a similar reaction pathway.

Synthesis of Functionalized 1,3-Butadienes via Pd-Catalyzed Cross-Couplings of Substituted Allenic Esters in Water at Room Temperature.

An environmentally responsible, mild method for the synthesis of functionalized 1,3-butadienes is presented. It utilizes allenic esters of varying substitution patterns, as well as a wide range of boron-based nucleophiles under palladium catalysis, generating sp-sp2, sp2-sp2, and sp2-sp3 bonds. Functional group tolerance measured via robustness screening, along with room temperature and aqueous reaction conditions highlight the methodology's breadth and potential utility in synthesis.

Fluoride-Mediated α-Selective 1,6-Conjugate Addition of Allenic Esters to p-Quinone Methides.

An efficient and expedient fluoride-mediated α-selective 1,6-conjugate addition of allenic esters to para-quinone methides has been developed. The reaction exhibited an excellent substrate scope, and a wide range of α-diarylmethylated allenic esters were obtained in good to excellent yields. It was further shown that the strategy could be extended to isatin-derived quinone methides yielding allenic esters containing 3,3-disubstituted oxindoles. The tert-butyl ester of α-diarylmethylated allenoate was effectively converted into γ-butenolide through a Au/Ag catalyzed cyclization strategy.

Gold-Catalyzed Formal [4 + 2] Cycloaddition of 5-(Ethynylamino)pent-2-yn-1-yl Esters to 1,2,3,5-Tetrahydrobenzo[ g]quinolines.

A synthetic method to prepare 1,2,3,5-tetrahydrobenzo[ g]quinolines efficiently that relies on gold(I)-catalyzed cycloisomerization of 5-(ethynylamino)pent-2-yn-1-yl esters at room temperature under atmospheric conditions is described. The proposed reaction mechanism presents a unique instance of an in situ formed allenic ester and gold keteniminium species to undergo a formal [4 + 2] cycloaddition pathway.

Kinetic studies of conjugate addition of amines to allenic and acrylic esters and their correlation with antibacterial activities against Staphylococcus aureus

Kinetic reactivities of various allenic and acrylic esters in conjugate addition reactions with various amines were investigated. Competition experiments showed that amines reacted selectively with allenic esters, which was also confirmed by quantitative determination of the rate constants. The antibacterial activity against Staphylococcus aureus of allenic and acrylic ester derivatives were also determined. Allenic esters were found to exhibit a higher antibacterial activity than its acrylic counterparts. A correlation between the kinetic property and the antibacterial activity suggested that a conjugate addition may involve in the antibacterial mechanism of these unsaturated esters.

Diastereoselective Synthesis of C-Vinyl Glycosides via Gold(I)-Catalyzed Tandem 1,3-Acyloxy Migration/Ferrier Rearrangement.

A novel gold-catalyzed C-glycosylation has been developed to gain access to α,(Z)-selective C-vinyl glycosides, starting from readily available glycals and propargylic carboxylate. This reaction involves a tandem intermolecular gold-catalyzed 1,3-acyloxy migration/Ferrier rearrangement with the involvement of allenic ester as the glycosyl acceptor. A wide range of substrate scope with good to excellent yields was achieved with complete diastereoselectivity.

Selective Palladium-Catalyzed Allenic C-H Bond Oxidation for the Synthesis of [3]Dendralenes.

A highly selective palladium-catalyzed allenic C-H bond oxidation was developed, and it provides a novel and straightforward synthesis of [3]dendralene derivatives. A variety of [3]dendralenes with diverse substitution patterns are accessible with good efficiency and high stereoselectivity. The reaction tolerates a broad substrate scope containing various functional groups on the allene moiety, including ketone, aldehyde, ester, and phenyl groups. Also, a wide range of olefins with both electron-donating and electron-withdrawing aryls, acrylate, sulfone, and phosphonate groups are tolerated.

Selective Palladium‐Catalyzed Allenic C−H Bond Oxidation for the Synthesis of [3]Dendralenes

AbstractA highly selective palladium‐catalyzed allenic C−H bond oxidation was developed, and it provides a novel and straightforward synthesis of [3]dendralene derivatives. A variety of [3]dendralenes with diverse substitution patterns are accessible with good efficiency and high stereoselectivity. The reaction tolerates a broad substrate scope containing various functional groups on the allene moiety, including ketone, aldehyde, ester, and phenyl groups. Also, a wide range of olefins with both electron‐donating and electron‐withdrawing aryls, acrylate, sulfone, and phosphonate groups are tolerated.

Enantioselective Reactions of 2‐Sulfonylalkyl Phenols with Allenic Esters: Dynamic Kinetic Resolution and [4+2] Cycloaddition Involving ortho‐Quinone Methide Intermediates

AbstractWe report herein a dynamic kinetic resolution (DKR) involving ortho‐quinone methide (o‐QM) intermediates. In the presence of Et3N and the cinchonine‐derived nucleophilic catalyst D, the DKR of 2‐sulfonylalkyl phenols with allenic esters afforded chiral benzylic sulfones in 57–79 % yield with good to excellent enantioselectivity (85–95 % ee). Furthermore, with 2‐(tosylmethyl)sesamols or 2‐(tosylmethyl)naphthols, from which stable o‐QM substrates can be generated, a formal [4+2] cycloaddition delivered 4‐aryl‐ or alkyl‐substituted chromans with excellent enantioselectivity (88–97 % ee).