Allene Chemistry Research Articles

Palladium-Catalyzed Asymmetric Cycloaddition/Cope Rearrangement Relay: Synthesis of Chiral Endocyclic Allenes

AbstractThe synthesis of chiral endocyclic allenes, especially the medium-sized ones, remains a challenge in allene chemistry due to unfavorable tension and difficult stereocontrol. Herein, an efficient protocol for the construction of chiral nine-membered endocyclic allenes via palladium-catalyzed asymmetric cycloaddition/Cope rearrangement relay of vinyl carbonates with activated enynes is highlighted. This process provides rapid access to a variety of chiral nine-membered endocyclic allenes in good yields with excellent enantioselectivities. In particular, a chiral P,S-ligand shows good performance on stereoinduction, generating central and axial chirality in a single transformation, which is rationalized by DFT calculations and by a proposed transition state.1 Introduction2 Pd-Catalyzed Asymmetric Cycloaddition/Cope Rearrangement Relay3 Plausible Mechanism and Stereochemical Outcome4 Conclusion and Outlook

Synthesis of Chiral Endocyclic Allenes by Palladium-Catalyzed Asymmetric Annulation Followed by Cope Rearrangement.

Catalytic asymmetric synthesis of chiral endocyclic allenes remains a challenge in allene chemistry owing to unfavored tension and complex chirality. Here, we present a new relay strategy merging Pd-catalyzed asymmetric [3+2] annulation with enyne-Cope rearrangement, providing a facile route to chiral 9-membered endocyclic allenes with high efficiency and enantioselectivity. Moreover, theoretical calculations and experimental studies were performed to illustrate the critical, but unusual Cope rearrangement that allows for the complete central-to-axial chirality transfer.

Synthesis of Chiral Endocyclic Allenes by Palladium‐Catalyzed Asymmetric Annulation Followed by Cope Rearrangement

AbstractCatalytic asymmetric synthesis of chiral endocyclic allenes remains a challenge in allene chemistry owing to unfavored tension and complex chirality. Here, we present a new relay strategy merging Pd‐catalyzed asymmetric [3+2] annulation with enyne‐Cope rearrangement, providing a facile route to chiral 9‐membered endocyclic allenes with high efficiency and enantioselectivity. Moreover, theoretical calculations and experimental studies were performed to illustrate the critical, but unusual Cope rearrangement that allows for the complete central‐to‐axial chirality transfer.

Synthesis of 5H-chromeno[3,4-b]pyridines via DABCO-catalyzed [3 + 3] annulation of 3-nitro-2H-chromenes and allenoates.

The DABCO-catalyzed [3 + 3] annulation between 3-nitro-2H-chromenes and benzyl 2,3-butadienoate has been developed as a route to 5H-chromeno[3,4-b]pyridine derivatives. Under optimal reaction conditions, 5H-chromeno[3,4-b]pyridines incorporating two allenoate units were obtained in moderate to good yields (30-76%). The same type of transformation could be carried out using butynoates as allene surrogates. Mechanistic studies by mass spectrometry allowed the identification of the key intermediates involved in the reaction mechanism. The reported synthetic methodology represents an entirely new approach for the synthesis of the 5H-chromeno[3,4-b]pyridine core structure based on allene chemistry.

Palladium-catalyzed C-P cross-coupling of allenic alcohols with H-phosphonates leading to 2-phosphinoyl-1,3-butadienes.

The first facile, efficient, atom-economical and regioselective palladium-catalyzed direct C-P cross-coupling of unprotected allenic alcohols with H-phosphonates for the one-pot synthesis of structurally diverse multisubstituted 2-phosphinoyl-1,3-butadienes was developed. This strategy would enrich the allene chemistry and afford new scaffolds to construct complex molecular skeletons.

Phosphine‐Catalyzed [3+2] and [2+4] Annulations of γ‐Methyl Allenoates with Aryl α‐Keto Esters: Stereoselective Syntheses of Functionalized Tetrahydrofurans and 4‐Chromanols

AbstractPhosphine‐catalyzed [3+2] and [2+4] annulation reactions of γ‐methyl allenoates with aryl α‐keto esters are described. Under the catalysis of triarylphosphine, γ‐methyl allenoates participate in both the [3+2] annulation with aroylformates and [2+4] annulation with ortho‐hydroxy aroylformates smoothly to bring about functionalized tetrahydrofurans and 4‐chromanols, respectively, in moderate to excellent yields with high stereoselectivity. The reactions herein also represent rare successful examples of phosphine‐catalyzed allene−ketone transformations, and further expand the scope of ketones in allene chemistry under phosphine catalysis.

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.

Exploring allene chemistry using phosphorus-based allenes as scaffolds

Abstract In this paper, we review some of our results on cycloaddition and cyclization reactions of allenylphosphonates/and allenyl phosphine oxides. Thus nitro-substituted propargylic alcohols react with P(III)–Cl substrates to lead to unprecedented phosphono-benzazepines or -hydroxyindolinones. A similar reaction using a higher stoichiometry of P(III)–Cl precursor has led to the first observation of spontaneous resolution by crystallization in allene chemistry. In the reaction of these phosphorus based allenes with diphenyl isobenzofuran (DPBF), depending on the substituents, both [α, β] and [β, γ]-cycloaddition products are formed. Extension of this work to sulfur based allenes and leading to a new [4+2] cycloadduct with DPBF is reported. A novel cyclization reaction of a functionalized allenylphosphine oxide with diethylamine leading to 3-diethylamino-4-diphenylphosphinoyl-1-naphthol is discovered. Base-catalyzed reactions of allenylphosphonates with 2-substituted benzaldehdes lead to novel thiochromans, chromenes, and quinolines. Allenylphosphonates undergo phosphonylation in the presence of tetrabutyl ammonium fluoride (TBAF). Vinyl azides derived from allenylphosphonates undergo thermolysis to form bis-phosphonopyrazines. [Pd]-catalyzed reactions of allenes with 2-iodophenols, 2-iodobenzyl alcohol and 3-iodo-indole-2-carboxylic acids lead to a variety of benzofurans, benzopyrans and benzopyranones, respectively.

Unique Reactivity of α‐Substituted Electron‐Deficient Allenes using Sulfinate Salts as Lewis Base Organocatalysts

AbstractThe efficient sulfinate‐catalyzed intermolecular addition reaction of α‐substituted allenyl sulfones and allenoates with Michael acceptors is highlighted. The sequence proceeds under mild conditions to provide a scalable and efficient access to versatile functionalized alkynes, displaying a quaternary stereocentre at the propargylic position. This work enriches the diversity of Lewis base organocatalysts in the field of allene chemistry, in addition to the well‐established phosphine and amine catalysts.magnified image

3-Imidoallenylphosphonates: In Situ Formation and β-Alkoxylation.

3-Imidoallenylphosphonates, allenes bearing both an electron-withdrawing and -donating group, were isolated for the first time. An alkoxy substituent was introduced into these unprecedented intermediates in a one-pot approach, yielding β-functionalized aminophosphonates in excellent yields and short reaction times. The mechanistic insights gained are important additions to the domain of allene chemistry. Addition of biologically important molecules, including monoglycerides, amino acids, and nucleosides, proves the general applicability of the developed method.

ChemInform Abstract: α‐Allenyl Ethers as Starting Materials for Palladium Catalyzed Suzuki—Miyaura Couplings of Allenylphosphine Oxides with Arylboronic Acids.

We disclose here the first palladium-catalyzed Suzuki–Miyaura couplings of aryl ethers functionalized allenylphosphine oxides with arylboronic acids. This new methodology with α-allenyl ethers as starting materials provides a novel approach to generate phosphinoyl 1,3-butadienes and derivatives with medium to excellent yields. The reaction tolerates a variety of functional groups to afford ranges of structurally diverse substituted phosphionyl 1,3-butadienes. For unsymmetrical allene substrates, high stereospecific additions to give E-isomers are usually observed. On the basis of the known palladium and allene chemistry, a mechanism is proposed.

Spontaneous resolution upon crystallization of allenyl-bis-phosphine oxides.

The first example of 'spontaneous resolution by crystallization' in allene chemistry, by means of crystal structures and solid state CD spectra of the R and S enantiomers, is presented. These allenes are prepared by the simple reaction of Ph2PCl with o-nitro functionalized propargyl alcohols.

α-Allenyl Ethers as Starting Materials for Palladium Catalyzed Suzuki-Miyaura Couplings of Allenylphosphine Oxides with Arylboronic Acids.

We disclose here the first palladium-catalyzed Suzuki-Miyaura couplings of aryl ethers functionalized allenylphosphine oxides with arylboronic acids. This new methodology with α-allenyl ethers as starting materials provides a novel approach to generate phosphinoyl 1,3-butadienes and derivatives with medium to excellent yields. The reaction tolerates a variety of functional groups to afford ranges of structurally diverse substituted phosphionyl 1,3-butadienes. For unsymmetrical allene substrates, high stereospecific additions to give E-isomers are usually observed. On the basis of the known palladium and allene chemistry, a mechanism is proposed.

ChemInform Abstract: Gold‐Catalyzed Cyclization Reactions of Allenol and Alkynol Derivatives

AbstractReview: 53 refs.

Gold-Catalyzed Cyclization Reactions of Allenol and Alkynol Derivatives

Although gold is chemically inert as a bulk metal, the landmark discovery that gold nanoparticles can be effective catalysts has opened up new and exciting research opportunities in the field. In recent years, there has been growth in the number of reactions catalyzed by gold complexes [gold(I) and gold(III)], usually as homogeneous catalysts, because they are soft Lewis acids. In addition, alkynes and allenes have interesting reactivities and selectivities, notably their ability to produce complex structures in very few steps. In this Account, we describe our work in gold catalysis with a focus on the formation of C-C and C-O bonds using allenes and alkynes as starting materials. Of these, oxa- and carbo-cyclizations are perhaps the best known and most frequently studied. We have divided those contributions into sections arranged according to the nature of the starting material (allene versus alkyne). Gold-catalyzed carbocyclizations in allenyl C2-linked indoles, allenyl-β-lactams, and allenyl sugars follow different mechanistic pathways. The cyclization of indole-tethered allenols results in the efficient synthesis of carbazole derivatives, for example. However, the compound produced from gold-catalyzed 9-endo carbocyclization of (aryloxy)allenyl-tethered 2-azetidinones is in noticeable contrast to the 5-exo hydroalkylation product that results from allenyl sugars. We have illustrated the unusual preference for the 4-exo-dig cyclization in allene chemistry, as well as the rare β-hydride elimination reaction, in gold catalysis from readily available α-allenols. We have also observed in γ-allenols that a (methoxymethyl)oxy protecting group not only masks a hydroxyl functionality but also exerts directing effects as a controlling unit in a gold-catalyzed regioselectivity reversal. Our recent work has also led to a combined experimental and computational study on regioselective gold-catalyzed synthetic routes to 1,3-oxazinan-2-ones (kinetically controlled products) and 1,3-oxazin-2-one derivatives (thermodynamically favored) from easily accessible allenic carbamates. In addition, we discuss the direct gold-catalyzed cycloketalization of alkynyldioxolanes, as well as aminoketalization of alkynyloxazolidines. We performed labeling studies and density functional calculations to gain insight into the mechanisms of the bis-heterocyclization reactions. We also describe the controlled gold-catalyzed reactions of primary and secondary propargylic hydroperoxides with a variety of nucleophiles including alcohols and phenols, allowing the direct synthesis of β-functionalized ketones. Through computations and (18)O-labeling experiments, we discovered various aspects of the controlled reactivity of propargylic hydroperoxides with external nucleophiles under gold catalysis. The mechanism resembles a Meyer-Schuster rearrangement, but notably, the presence and geometry characteristics of the OOH functional group allow a new pathway to happen, which cannot apply to propargylic alcohols.

Progress in allene chemistry

Progress in allene chemistry

Development of a Nonenzymatic Kinetic Resolution of α-Allenic Alcohols

This personal viewpoint lays out the development of a silver-catalyzed kinetic resolution of alpha-allenic alcohols inspired by the biomimetic synthesis of natural products. The corresponding selectivity factor (s) indicates that this resolution protocol can deliver chiral allenic alcohols and 2,5-dihydrofurans in high enantioselectivity with synthetically applicable isolated yields. The broad substrate scope makes it an attractive approach for building synthetically useful chiral building blocks. From the recent progress in allene chemistry, silver was considered as an anion metathesis reagent to prepare highly efficient Au catalysts. Our discovery of the unique reactivity of a chiral silver phosphate should stimulate more interesting discoveries in this field.

“Total Synthesis of Bioactive Natural Products by Palladium-Catalyzed Domino Cyclization of Allenes and Related Compounds”

Chemistry Research Laboratory, University of Oxford, 12 Mansfi eld Road, Oxford OX1 3TA, UK Email: edward.anderson@chem.ox.ac.uk In the latest contribution to the “Springer Theses” series, which celebrate outstanding graduate research from the physical sciences, Shinsuke Inuki provides a detailed account of his PhD research, entitled “Total Synthesis of Bioactive Natural Products by Palladium-Catalyzed Domino Cyclization of Allenes and Related Compounds”. Inuki carried out this work in the laboratory of Professor Hiroaki Ohno (Kyoto University, Japan), whose young research group has established a reputation in the fi eld of late transition metal-catalysed ‘cascade’ organic reactions (also known as ‘domino’ reactions) involving alkynes and allenes. The target audience for the book includes practicing organic chemists with interests in synthesis, and those with specifi c interests in palladium-catalysed organic reactions, and as such is suited to graduate level and above. As the title suggests, the book delves extensively into mechanistic aspects of palladium-catalysed allene chemistry, with a focus on two reaction types: intramolecular reactions of allenylpalladium(II) complexes with pendant nucleophiles, and intramolecular reactions of allenes activated by pendant palladium(II) species (Scheme I). The key feature of these processes is the ability of the palladium(II) catalyst to enhance the electrophilicity of the allene through coordination to the metal atom in its +2 oxidation state, thus triggering nucleophilic attack. Having established an understanding of each metal-catalysed bicyclisation, Inuki goes on to apply this chemistry to the synthesis of a number of bioactive alkaloid natural products. The overall aims of the work are fi rstly to extend the state of the art in palladium-activated allene chemistry through a “Total Synthesis of Bioactive Natural Products by Palladium-Catalyzed Domino Cyclization of Allenes and Related Compounds”

Applications of the in situ Propargyl-Allenyl Isomerization in Organic Synthesis

Allenes have been shown to be versatile building blocks in organic synthesis. However, the diversity of the allene chemistry offers a challenging and exquisite task for organic chemists bent on building the suitable allene substrates. A good solution might be propargyl-allenyl isomerization, which means to prepare readily available propargyl substrates. This review focuses on recent progress in the in situ propargyl-allenyl isomerization in organic synthesis, published in 1990 and later.

ChemInform Abstract: How Easy Are the Syntheses of Allenes?

AbstractReview: 309 refs.