Allenyl Group Research Articles

Nickel-Catalyzed Photoredox Allenylation of Alkyl Halides.

We report a dual Ni/photoredox-catalyzed cross-coupling method for propargyl carbonates and nonactivated alkyl bromides, facilitating the synthesis of a variety of substituted allenes under mild and practical conditions. Mechanistically, the reaction integrates Ni-catalyzed activation of the propargyl electrophile via SN2' oxidative addition at Ni(I) with silyl radical-induced activation of the alkyl halide through halogen-atom transfer. This methodology provides a gentle approach for introducing allenyl groups into complex halogenated aliphatic molecules, offering further opportunities for derivatization.

Chemoselectivity Switch between Enantioselective [2,3]-Wittig Rearrangement and Conia-Ene-Type Reactions of Propargyloxyoxindoles.

Despite the existence of three competing reactions for propargyloxyoxindoles, we report a chemoselectivity switch between enantioselective propargyl [2,3]-Wittig rearrangement and Conia-ene-type reactions, with suppression of the [1,2]-Wittig-type rearrangement. Using C1-symmetric imidazolidine-pyrroloimidazolone pyridine as the ligand and Ni(acac)2 as the Lewis acid, diverse 3-hydroxy 3-substituted oxindoles containing allenyl groups were obtained in up to 98 % yield and 99 % ee via asymmetric propargyl [2,3]-Wittig rearrangement. In the presence of AgOTf-Duanphos, chiral spiro dihydrofuran oxindoles were given in up to 98 % yield and 91 % ee through a Conia-ene-type reaction.

Stereodivergent Synthesis of Allenes with α,β‐Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis

AbstractThe stereodivergent synthesis of allene compounds bearing α,β‐adjacent central chiralities has been realized via the Pd/Cu‐catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl‐substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non‐natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommonη3‐butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2−Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT).

Stereodivergent Synthesis of Allenes with α,β-Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis.

The stereodivergent synthesis of allene compounds bearing α,β-adjacent central chiralities has been realized via the Pd/Cu-catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl-substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non-natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo- and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommon η3 -butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2 -Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT).

The [3]Dendralene Motif as an Entry into Nazarov Cyclizations by Silylium-Ion Initiation

Geminal alkenes bearing an aryl and an allenyl group contain the motif of [3]dendralenes. The central alkene double bond in these cross-conjugated polyenes can be reacted with a silylium ion, thereby initiating a Nazarov cyclization. The cationic intermediate emerging from the electrocyclic ring closure is captured by hydride in the presence of excess hydrosilane. The resulting benzannulated methylenecyclopentene derivatives bearing a silylalkyl group then engage in silylium-ion regeneration followed by an unusual endo-selective intramolecular hydrosilylation. This cascade eventually leads to the formation of a silicon-containing bicyclo[3.2.1]octane skeleton.

A mild method for the replacement of a hydroxyl group by halogen: 3. the dichotomous behavior of α-haloenamines towards allylic and propargylic alcohols

A study of the deoxyhalogenation of allylic and propargylic alcohols with tetramethyl-α-halo-enamines is reported. Primary allylic and primary and secondary propargylic alcohols gave the corresponding halides in high yields. Secondary allylic and propargylic alcohols yielded the corresponding secondary halides but the reaction also produced some rearranged primary halides (I > Br > Cl). The reactions with tertiary allylic and tertiary propargylic alcohols gave several products and was therefore of little synthetic value. However, the addition of triethylamine to the reaction mixture or the use of lithium alkoxide instead of alcohol brought about a major change of the course of the reaction which led to amides carrying an allyl or an allenyl group at C 2 . This was shown to result from a Claisen-Eschenmoser rearrangement of an intermediate α-allyloxy- or propargyloxy-enamine.

Formation of o-Allyl- and Allenyl-Modified Amides via Intermolecular Claisen Rearrangement.

We developed a new transition-metal-free intermolecular Claisen rearrangement process to introduce allyl and allenyl groups into the α position of tertiary amides. In this transformation, amides were activated by trifluoromethanesulfonic anhydride to produce the keteniminium ion intermediates that exhibit strong electrophilic activity. This atom-economical process delivers α position-modified amides under mild conditions in moderate to good yields and showcases a broad substrate compatibility.

Acid-catalyzed allenylation of pyrazolones with propargyl alcohols

A TsOH-catalyzed allenylation of pyrazolones with propargylic alcohols has been developed. The established reaction system is well tolerated by a wide scope of pyrazolones and propargylic alcohols. The process has the salient features of operational simplicity, facile scale-up and high yield. In particular, the integration of the pharmaceutical-related pyrazolone skeleton and the allenyl group into a single molecule not only enriches the structural diversity of the pyrazolone scaffold, but potentially also contributes to a broader spectrum of biological activity. Furthermore, it is easy to synthesize 3aa in gram-scale with the yield and efficiency basically maintained, making the practical application of this process more prominent.

Synthesis of Azocane- and Oxocane-Annulated Furans by a [2+2] Photocycloaddition–Ring-Opening Cascade

AbstractThe title compounds were synthesized from readily available quinolone and coumarin derivatives by a cascade reaction (12 examples, 90–98% yield). The cascade comprised a [2+2] photocycloaddition which occurred upon sensitized irradiation at λ = 420 nm (or direct UV irradiation at λ = 366 nm) and a subsequent acid-catalyzed ring-opening reaction. A variety of substituents are compatible with the conditions and a 3-alkyl group in the coumarin (or quinolone) is crucial to achieve a high chemoselectivity. Key to the success of the ring opening is the formation of a 4,5,5a-trihydrocyclobuta-2H-furan containing a strained bridgehead double bond which stems from the allenyl group tethered to the 4-position of the starting materials.

A Comparison between the Cycloadditions of Allenyl- and Vinyl-Cyclopentanes Using Density Functional Theory and GRRM Program.

Cycloaddition catalyzed by transition metals such as rhodium (I) is an important way to synthesize functionalized molecules in medicinal chemistry. When the reagent has a saturated ring containing more than five carbons (or heavy atoms), the reaction can progress when the compound has an allenyl group, but not for a vinyl group. Here, we constructed two computational models for allenylcyclopentane-alkyne and vinylcyclopentane-alkyne, and obtained their reaction pathways using density functional theory (DFT). From the reaction pathways, we confirmed that the former model has a much lower reaction energy than the latter. We also found that the molecular orbitals of the transition state structure at the rate-controlling step contribute significantly to the difference in reactivity between the two models.

Effect of ring size on the properties of μ3-Cycloalkyne complexes: Synthesis of triruthenium complexes containing a perpendicularly coordinated μ3-Allenyl ligand

A series of triruthenium complexes, [{Cp*Ru(μ-H)}3(μ3-η2:η2-CnH2n-4)] (2a, n = 6; 2b, n = 7; 2c,n = 8), containing a triply bridgin cycloalkyne ligand was synthesized. Although no noticeable differences were detected in the ground state, the rate of dynamic motion of the cycloalkyne ligand increased remarkably as the ring size increased. Owing to the flexibility of the larger rings, an allylic CH bond can interact with one of the metal centers, stabilizing the transition state of the dynamic process. This interaction also caused allylic CH bond scission upon chemical oxidation. In the case of 2b and 2c, a cationic μ3-η2:η2:η2-allenyl complex, [{Cp*Ru(μ-H)}3(μ3-η2:η2:η2-CnH2n-5)]+ (3b, n = 7; 3c, n = 8), was obtained. X-ray diffraction studies of 3 clearly show that the allenyl group is coordinated to one of the Ru-Ru bonds in a perpendicular fashion, unlike the known "parallel" μ3-allenyl complexes. In contrast to the reactions of 2b and 2c, chemical oxidation of 2a occurred via the incorporation of adventitious H2O rather than intramolecular C-H bond cleavage. Consequently, cationic μ3-cyclohexyne-μ-hydroxo complex, [{Cp*Ru(μ-H)}3(μ-OH)(μ3-η2-C6H8)]+ (5a) was obtained in 38% yield by the reaction with 2 equiv [Cp2Fe]+ in the presence of excess water. These results clearly show that the reaction pathway of the μ3-cycloalkyne complex varies with the ring size.

N-Heterocyclic Carbene-Cu-Catalyzed Enantioselective Allenyl Conjugate Addition.

A catalytic enantioselective conjugate addition with commercially available allenylboronic acid pinacol ester as nucleophile promoted by a chiral copper complex of N-heterocyclic carbene (NHC) is disclosed. This process constitutes an unprecedented instance of the conjugate addition that introduces an allenyl group into α,β-unsaturated carbonyl compounds, affording products that are otherwise difficult to access in up to 92% yield, >98% allenyl addition selectivity and 96:4 enantiomeric ratio. DFT calculations were performed to elucidate the origins of enantioselectivity.

Computational Mechanistic Analysis of Intramolecular Cycloadditions of the 1,3-Dithiolium Cation with Adjacent Alkene and Allene Functional Groups.

In this work, the molecular mechanisms for the intramolecular cycloaddition reactions of the 1,3-dithiolium cation with adjacent alkenyl and allenyl groups were investigated by density functional theory calculations. Transition states for the mechanistic steps were searched, and their connections to corresponding reactive intermediates were validated by the intrinsic reaction coordinate method. Our studies demonstrate that both the alkenyl and allenyl groups can readily react with a neighboring 1,3-dithiolium cation first through a one-step asynchronous [3 + 2] cycloaddition path, with moderate activation energy barriers (ca. 20–30 kcal/mol) to overcome. Subsequent to the intramolecular dithiolium–alkene/allene cycloadditions, the resulting intermediates continue to undergo a series of reactions, including rearrangement, ring opening, and deprotonation to eventually yield the thermodynamically favored products, which carry a fused tricyclic molecular skeleton, 3,8-dihydro-2H-indeno[2,1-b]thiophene. Detailed geometric and energetic properties for all of the stationary points (transition states and intermediates) on the reaction potential surfaces have been calculated and examined. Key transition states and reactive intermediates were subjected to quantum theory of atoms in molecules and natural bonding orbital calculations to elucidate their bonding features and the stabilizing effects arising from orbital interactions. Finally, a comparative study using the continuum solvation model based on the charge density was conducted to evaluate the solvent effects on the intramolecular dithiolium–alkene/allene cycloadditions, which are the rate-limiting steps of the overall reactions. The results show that different organic solvents (polar and nonpolar) do not lead to much variations in the heights of activation energy barriers and hence indicate that solvent effects are actually insignificant on the reactions.

Nickel(II)‐Catalyzed Asymmetric Propargyl [2,3] Wittig Rearrangement of Oxindole Derivatives: A Chiral Amplification Effect

AbstractA highly enantioselective [2,3] Wittig rearrangement of oxindole derivatives was realized by using a chiral N,N′‐dioxide/NiII complex as the catalyst under mild reaction conditions. A strong chiral amplification effect was observed, and allowed access to chiral 3‐hydroxy 3‐substituted oxindoles bearing allenyl groups in high yields and enantioselectivities (up to 92 % ee) by using a ligand with only 15 % ee. A reasonable explanation was given based on the experimental investigations and X‐ray crystal structures of enantiomerically pure and racemic catalysts. Moreover, the first catalytic kinetic resolution of racemic oxindole derivatives by a [2,3] Wittig rearrangement was realized with high efficiency and stereoselectivity.

Nickel(II)-Catalyzed Asymmetric Propargyl [2,3] Wittig Rearrangement of Oxindole Derivatives: A Chiral Amplification Effect.

A highly enantioselective [2,3] Wittig rearrangement of oxindole derivatives was realized by using a chiral N,N'-dioxide/NiII complex as the catalyst under mild reaction conditions. A strong chiral amplification effect was observed, and allowed access to chiral 3-hydroxy 3-substituted oxindoles bearing allenyl groups in high yields and enantioselectivities (up to 92 % ee) by using a ligand with only 15 % ee. A reasonable explanation was given based on the experimental investigations and X-ray crystal structures of enantiomerically pure and racemic catalysts. Moreover, the first catalytic kinetic resolution of racemic oxindole derivatives by a [2,3] Wittig rearrangement was realized with high efficiency and stereoselectivity.

ChemInform Abstract: Palladium‐Catalyzed Decarbonylative Rearrangement of N‐Allenyl Seleno‐ and Tellurocarbamates.

Decarbonylative rearrangement of seleno- and tellurocarbamates carrying an allenyl group on the nitrogen was found to proceed in the presence of a palladium catalyst to afford 3-chalcogeno-1-azadienes. This transformation may involve oxidative addition of Pd to a carbon–chalcogen bond, decarbonylation from a carbamoylpalladium unit (R2N-C(O)-PdChPh: Ch = Se or Te), Pd shift, and reductive elimination.

ChemInform Abstract: First Iodocyclization Reaction of Allene—Thioureas: An Efficient Approach to Bicyclic β‐Lactams.

AbstractDepending on the substituents on the allenyl group of the substrates the regioselective iodocyclization provides either six‐membered 3‐thia‐1‐dethiacephems or seven‐membered thiazepines in a mixture with five‐membered isopenams.

Truncateols A–N, new isoprenylated cyclohexanols from the sponge-associated fungus Truncatella angustata with anti-H1N1 virus activities

Fourteen new isoprenylated cyclohexanols namely truncateols A–N (1–14) were isolated from the solid culture of the sponge-associated fungus Truncatella angustata. Their structures were determined on the basis of extensive spectroscopic analyses, including the modified Mosher's method and ECD, as well as X-ray diffraction for the assignment of absolute configurations. The structures of truncateols are characterized by the presence of unique alkynyl or allenyl groups. Truncateol M (13) exerted potent inhibitory effect against influenza-A viral infection by targeting virion assembly/release step.

Palladium‐Catalyzed Decarbonylative Rearrangement of N‐Allenyl Seleno‐ and Tellurocarbamates

ABSTRACTDecarbonylative rearrangement of seleno‐ and tellurocarbamates carrying an allenyl group on the nitrogen was found to proceed in the presence of a palladium catalyst to afford 3‐chalcogeno‐1‐azadienes. This transformation may involve oxidative addition of Pd to a carbon–chalcogen bond, decarbonylation from a carbamoylpalladium unit (R2N‐C(O)‐PdChPh: Ch = Se or Te), Pd shift, and reductive elimination.

ChemInform Abstract: Regulation of Diastereoselectivity in the Carbocyclization of Allenyl (S)‐N‐tert‐Butylsulfinimines Through a Three‐Component Assembly.

AbstractA diastereoselective carbocyclization with readily available sulfinimines is described.