Allenic Acids Research Articles

Utilizing Allenic Acids and Heterocyclic Diazo Compounds in the Synthesis of Polysubstituted Spirocyclic Butenolides and β-Methylidene 2-Furanones.

Herein, we report a novel approach for the assembly of spirocyclic Δα,β-butenolides and β-methylidene 2-furanones via Rh(II)-catalyzed O-H insertion of heterocyclic diazo compounds into allenic acids followed by base-promoted cyclization. Utilizing various diazo heterocycles, including α-diazo homophthalimides, 3-diazo tetramic acids, and diazo oxindoles, diverse spirocyclic scaffolds were produced. The research revealed that the allenic acid substitution pattern is decisive for the product type, enabling extraordinary target compound switching between two types of spirocyclic 2-furanones with exo- and endocyclic C═C bonds.

Synthesis of Pyrrolidin-5-one-2-carboxamides through Cyclization of N-Substituted-2-alleneamides

The synthesis of pyrrolidin-5-one-2-carboxamides 6a-p has been developed via a one-pot Ugi reaction of allenic acids, primary amines, isocyanides, and aldehydes followed by regioselective cyclization of the resultant N-substituted-2-allenamides with KOt-Bu at room temperature. The cyclization reaction was carried out through a 5-exo-dig approach, which resulted in good yields and high atom-economy under transition-metal-free and mild reaction conditions.

Review: Pharmacological Activity, Chemical Composition and Medical Importance of Leonotis nepetifolia R.Br.

India is perhaps the most unique country in the world, with the richest tradition of indigenous and health care medical practices. Most of these practices are unique and known to very few individuals or communities. Leonotis nepetifolia Family (Lamiaceae) commonly known as ‘Klip dagga’ which has a long history of several traditional medicinal uses in many countries in the world. A huge number of phytoconstituents have been reported from the plant are allenic acid, iridoids, glycosides, terpenoids, and many more. This plant exhibited various biological activities and has been attributed to a variety of physiological effects like antifungal, antidiabetic, anxiolytic, arthritic, and many more activities. This literature review presents important species covering phytochemistry and pharmacological activities aspects systematically.

Synthesis of biologically active heterocyclic compounds from allenic and acetylenic nitriles and related compounds

Abstract Cyclic and polycyclic compounds containing moieties such as imidazole, pyrazole, isoxazole, thiazoline, oxazine, indole, benzothiazole and benzoxazole benzimidazole are prized molecules because of the various pharmaceutical properties that they display. This led Prof. Landor and co-workers to engage in the synthesis of several of them such as alkylimidazolenes, oxazolines, thiazolines, pyrimidopyrimidines, pyridylpyrazoles, benzoxazines, quinolines, pyrimidobenzimidazoles and pyrimidobenzothiazolones. This review covers the synthesis of biologically active heterocyclic compounds by the Michael addition and the double Michael addition of various amines and diamines on allenic nitriles, acetylenic nitriles, hydroxyacetylenic nitriles, acetylenic acids and acetylenic aldehydes. The heterocycles were obtained in one step reaction and in most cases, did not give side products. A brief discussion on the biological activities of some heterocycles is also provided.

Total Syntheses of Atrovenetin and Atrovenetinone: A Naphthalene-Annulation Approach to a Discoid Tricycle Using Allenic Acid

A total synthesis of atrovenetin has been achieved. The discoid tricyclic motif was constructed by a novel three-carbon annulation of naphthalene derivative and allenic acid under acidic conditions. An effective protocol for the conversion of atrovenetin into atrovenetinone has been established.

Ugi/Himbert Arene/Allene Diels-Alder Cycloaddition to Synthesize Strained Polycyclic Skeleton.

The present work disclosed an efficient multicomponent reaction of isocyanide, allenic acid, aldehyde (ketone), and aniline. This protocol undergoes Ugi reaction followed by an intramolecular arene/allene Diels-Alder sequence, thus providing a rapid access to synthesize strained polycyclic skeletons.

ChemInform Abstract: Taming the Carboxyl Group for Directed Carbometalation: Observations on the Use of Anions, Dianions and Ester Enolates.

AbstractThe copper‐mediated directed metalation of allenic acid (I) and ester (XIV) is investigated to yield β,γ‐unsaturated products (III) and (XV) regioselectively.

Synthesis and Reactivity of β,γ-Dihalogenated Unsaturated Acids: Application to the Synthesis of 4-Substituted 5H-Furan-2-ones

β,γ-Dihalogenated unsaturated acids were prepared regio- and stereoselectively from allenic acid, and some aspects of their reactivities were studied.

ChemInform Abstract: Cycloaddition of Carbodiimides with a Heteroaromatic Substituent to Allenic Acids.

Cycloaddition of the allenic acid 3 with the N -cyclohexyl-N′ -heteroaromatic carbodiimides 2a and 2b gave the isomeric pyrido[1,2-a]pyrimidinones 4 and 5 and thiazolo[3,2-a]pyrimidinones 6 and 7, respectively, instead of the expected Diels-Alder adducts analogous to 1. The compounds of the latter type, i.e.8 and 9, were formed from 3 and carbodiimides 2c and 2d, respectively, containing an N′-(pyrazin-2-yl) or N′-(pyrimidin-2-yl) substituent.

ChemInform Abstract: Preparation of a Serine-Derived Organozinc Reagent in Tetrahydrofuran: Synthesis of Novel, Enantiomerically Pure Allenic, Acetylenic, and Heteroaryl Amino Acids.

ChemInform Abstract: Preparation of a Serine-Derived Organozinc Reagent in Tetrahydrofuran: Synthesis of Novel, Enantiomerically Pure Allenic, Acetylenic, and Heteroaryl Amino Acids.

ChemInform Abstract: Stereoselective Total Synthesis of the Pseudopterolide Kallolide A.

A total synthesis of the pseudopterolides, kallolide A (36) and kallolide A acetate (35), has been achieved. The racemic forms were prepared from the syn adduct 20 of furan 13 and stannane 17 (BF(3).OEt(2)-promoted addition) via the 15-membered propargylic allylic ether 25. [2,3]Wittig ring contraction led to the cis, anti, cis product 26. Alcohol 26 was transformed to butenolide 34 with net retention of configuration by Pd(PPh(3))(4)-catalyzed carbonylation of the mesylate 27 and ensuing AgNO(3)-catalyzed cyclization of the derived allenic acid 29. Solvolysis of the SEM ether (at C2) 34 in acetic acid or aqueous t-BuOH afforded racemic kallolide A acetate (35) and kallolide A (36), respectively, with inversion of stereochemistry by an S(N)1 process. Key elements of stereocontrol, including the steric outcome of the [2,3]Wittig ring contraction, the allenic ester isomerization, and the solvolysis reactions, were predicted from molecular mechanics calculations. The C8 and C2 epimers 45 and 46 of the cis, anti, cis kallolide A SEM ether precursor 34 were also prepared. The synthetic route originated from the anti adduct 19 of aldehyde 13 and the allylic chloride 16 and CuCl (cat), HSiCl(3), and i-Pr(2)NEt. Adduct 19 was subjected to the same sequence as the syn counterpart 20 to produce the trans, anti, cis [2,3]Wittig ring contraction product 42. The derived allenoate 44 afforded a 1:1 mixture of butenolides 45 and 46 upon sequential treatment with TBAF and AgNO(3). Finally, the natural enantiomer (+)-36 of kallolide A was synthesized from the enantioenriched syn adduct (+)-20, prepared by addition of allylic stannane 17 to aldehyde 13 promoted by a modified chiral acyloxyborane Lewis acid.

Allene epoxidation: synthesis of functionalized lactones by the DMDO oxidation of allenic acids

A series of allenic carboxylic acids has been converted to functionalized lactones by oxidation–cyclization promoted by dimethyldioxirane. These transformations are rationalized by the involvement of unisolated allene oxide and spirodioxide intermediates. The structures of the starting allenic acids and the reaction conditions determine which of these two intermediate species serves as the source of the isolated products. The use of prepared solutions of the oxidant generally proceed via spirodioxides; whereas in situ reactions normally give products derived from the allene oxides. When products are formed directly from allene oxides, keto lactones are formed. The corresponding spirodioxide intermediates give lactones with appropriately situated α-hydroxyketone moieties. An understanding of the regiochemistry of the epoxidations and the subsequent cyclizations of the reactive intermediates is developed, as are methods for the manipulation of the experimental conditions to favor the desired products.

Regioselective Cationic 1,2- and 1,4-Additions Forming Carbon−Carbon Bonds to Methyl Santalbate, a Conjugated Enyne

Lewis acid-induced carbocationic addition reactions to methyl santalbate [methyl (E)-octadec-11-en-9-ynoate] [(E)-1] give products by regioselective formation of a new carbon−carbon bond at C-9 of the molecule chain. The allenic fatty acid derivatives methyl 12-chloro-9-(1-oxoheptyl)-9,10-octadecadienoate (2) and methyl 9-isopropyl-9,10-octadecadienoate (3) were obtained by Friedel−Crafts acylation of 1 with heptanoyl chloride and alkylation of 1 with isopropyl chloroformate, respectively. While the reaction between 1 and formaldehyde induced by Me2AlCl or Et3Al2Cl3 gives a mixture of the conjugated chlorodienes 5a and 5b, the corresponding reaction carried out in the presence of AlCl3 affords the α,β-unsaturated ketone 6.

Stereoselective Total Synthesis of the Pseudopterolide Kallolide A.

A total synthesis of the pseudopterolides, kallolide A (36) and kallolide A acetate (35), has been achieved. The racemic forms were prepared from the syn adduct 20 of furan 13 and stannane 17 (BF(3).OEt(2)-promoted addition) via the 15-membered propargylic allylic ether 25. [2,3]Wittig ring contraction led to the cis, anti, cis product 26. Alcohol 26 was transformed to butenolide 34 with net retention of configuration by Pd(PPh(3))(4)-catalyzed carbonylation of the mesylate 27 and ensuing AgNO(3)-catalyzed cyclization of the derived allenic acid 29. Solvolysis of the SEM ether (at C2) 34 in acetic acid or aqueous t-BuOH afforded racemic kallolide A acetate (35) and kallolide A (36), respectively, with inversion of stereochemistry by an S(N)1 process. Key elements of stereocontrol, including the steric outcome of the [2,3]Wittig ring contraction, the allenic ester isomerization, and the solvolysis reactions, were predicted from molecular mechanics calculations. The C8 and C2 epimers 45 and 46 of the cis, anti, cis kallolide A SEM ether precursor 34 were also prepared. The synthetic route originated from the anti adduct 19 of aldehyde 13 and the allylic chloride 16 and CuCl (cat), HSiCl(3), and i-Pr(2)NEt. Adduct 19 was subjected to the same sequence as the syn counterpart 20 to produce the trans, anti, cis [2,3]Wittig ring contraction product 42. The derived allenoate 44 afforded a 1:1 mixture of butenolides 45 and 46 upon sequential treatment with TBAF and AgNO(3). Finally, the natural enantiomer (+)-36 of kallolide A was synthesized from the enantioenriched syn adduct (+)-20, prepared by addition of allylic stannane 17 to aldehyde 13 promoted by a modified chiral acyloxyborane Lewis acid.

Palladium-catalyzed intramolecular 1,2-oxidation of allenes

Palladium(II)-catalyzed intramolecular 1,2-oxidation of allenic acids proceeds smoothly under mild conditions in the presence of LiBr and p-benzoquinone to give bromolactones in good to high yields.

アリルニッケル触媒によるアレン類のリビング配位重合の開拓と応用

This article describes our recent works on the living coordination polymerization of allene derivatives by allylnickel catalysts. The polymerization of alkoxyallenes by allylnickel catalysts proceeds via a living process to give polymers with predictable molecular weights and narrow molecular weight distributions in excellent yields. The polymerization was carried out with allylnickel complexes bearing various ligands to figure out the clear effect on the polymer structures and the polymerization behavior. Similarly, allene derivatives bearing various substituents such as phenylallene, alkylallenes, allenylsulfide, allenylpyrrolidone, allenyloxazolidone, esters of allenic acid, and macromonomers bearing allenyloxy end groups undertake the living polymerization. Macromolecular designs based on the living polymerization of allene derivatives (e.g., block copolymerizations) are also described.

ChemInform Abstract: Synthetic Routes to Allenic Acids and Esters and Their Stereospecific Conversion to Butenolides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Predictable chromatographic separations of enantiomers: aryl allenic acids and their derivatives

Designed to distinguish between the enantiomers of compounds having certain rather common structural features, the chiral selector used in chiral stationary phase (CSP) 1 columns is broadly applicable. The validity of the chiral recognition mechanism used to design the selector is supported by NMR and chromatographic studies and one can honestly claim to have a relatively good understanding of when and how this selector will differentiate between enantiomers. Consequently, one can often confidently predict not only that this column will separate the enantiomers of a given compound but also specify the relation between absolute configuration and elution order. A recent paper describing the use of a chiral allenic acid to aid in assigning absolute configurations by exciton-coupled circular dichroic measurements focused our attention on these allenes. A priori, these aromatic allenic acids appeared to contain structural features which would allow enantio-separation on CSP 1. Accordingly, a series of chiral allenic acids and their ester and amide derivatives were prepared for chromatographic study. Indeed, the enantiomers of the acids and esters are readily resolved, eluting in the expected order. The amides resolve more poorly for reasons that are clearly defined. Relevant data and mechanistic explanations are presented to convey an understanding of how CSP 1 differentiates between enantiomers.

Synthetic Routes to Allenic Acids and Esters and Their Stereospecific Conversion to Butenolides.

The synthesis of allenic acids and esters and their conversion to butenolides has been examined in some detail. Racemic butenolides 10 are efficiently prepared from the esters 8 through treatment with BCl(3) and exposure of the derived acid 9 to catalytic AgNO(3) in acetone. Conversion of the enantioenriched allenylstannane (S)-17 to the acid 18 through lithiation and subsequent carboxylation with CO(2) afforded racemic product. The enantioenriched propargylic mesylates 16 and 22 afforded the allenic esters 19 and 23 with inversion of configuration through treatment with Pd(Ph(3)P)(4), CO, and the appropriate alcohol in THF. These reactions proceeded with ca. 10% or less of racemization. The allenic esters 23 yielded the iodobutenolides 24 by reaction with IBr. Hydrogenolysis to the butenolide 25 was achieved with Pd(PPh(3))(4) and Bu(3)SnH. Alternatively, the allenic acids 27 could be prepared directly from mesylates 22 with Pd(PPh(3))(4) and CO in aqueous THF. Cyclization to the butenolides 25 was achieved, as before, with catalytic AgNO(3).

A new approach in exciton-coupled circular dichroism (ECCD)--insertion of an auxiliary stereogenic center.

There are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane-1,4-diols (both ee or ea) and a wide variety of 3-hydroxy carotenoids, 3-hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROM-CH = C = CH-COOH. The allenic bond introduces a 90 degrees twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases.