Δ-acetoxy Allenoates Research Articles

Synthesis of Isoxazol-5(2H)-one Derivatives via (tBuO)2Mg Promoted [3 + 2] Annulations of δ-Acetoxy Allenoates with Hydroxylamine.

Herein, an efficient (tBuO)2Mg promoted [3 + 2] annulation of δ-acetoxy allenoates with N-benzylhydroxylamine has been developed. This method provides a concise and facile protocol to synthesize vinylated isoxazol-5(2H)-one derivatives stereospecifically in a broad substrate scope with high efficiency (31 examples, up to 87% yield).

Divergent Reactivity of δ-Acetoxy Allenoates with 1,3-Bisnucleo­philes: Synthesis of Multisubstituted Pyran, Dihydropyran, and 3-Vinylpent-2-enedioate Scaffolds

AbstractBase-dependent synthesis of tetrasubstituted pyrans or 3,4-dihydropyrans using δ-acetoxy allenoates and enolizable carbonyls like cyclohexan-1,3-dione and ethyl benzoylacetate is reported. Thus, the use of DMAP as an organocatalytic base gives tetrasubstituted pyrans while DBU affords isomeric tetrasubstituted 3,4-dihydropyrans. The reaction of δ-acetoxy allenoates with ethyl benzoylacetate mediated by KO t Bu furnishes diethyl 3-vinylpent-2-enedioates.

δ-Acetoxy Allenoate as a 5C-Synthon in Domino-Annulation with Sulfamidate Imines: Ready Access to Coumarins.

A DMAP-catalyzed sequential benzannulation and lactonization strategy in which δ-acetoxy allenoate functions as a 5C-synthon in its reaction with cyclic sulfamidate imines is reported. This platform delivers π-extended coumarin frameworks under metal-free conditions via allylic elimination followed by Mannich coupling, proton shifts, C-N bond cleavage, and lactonization as key steps. The driving force for this domino reaction is the formation of the diene-ammonium intermediate and O-S bond cleavage. ESI-HRMS has been useful in gaining insights into the reaction pathway.

(3 + 3) Annulation of acetoxy allenoates with enolisable carbonyl substrates leading to fused pyrans.

Lewis base dependent (3 + 3) annulation of δ-acetoxy allenoates with benzofuranone, pyrazolone, and Boc-protected oxindole is reported. In the presence of catalytic DBU, oxindole, benzofuranone, and pyrazolone undergo (3 + 3) annulation with δ-acetoxy allenoates via 6-exo-dig cyclisation at room temperature (25 °C) to afford fused pyran scaffolds. On the other hand, by employing catalytic DMAP, the reaction between N-Boc-oxindole and δ-acetoxy allenoates goes through 6-endo-dig cyclisation, leading to distinct dihydropyrans that contain an exocyclic double bond; similar products were also obtained by using benzofuranone and pyrazolone.

NHC-catalyzed formal [3 + 3] annulations of δ-acetoxy allenoates for the synthesis of 4H-pyran derivatives.

Herein, an N-heterocyclic carbene (NHC) catalyzed formal [3 + 3] annulation of δ-acetoxy allenoates with 1C,3O-bisnucleophiles for the construction of 4H-(fused)pyrans has been developed. This protocol provides a facile method to synthesize highly functionalized 4H-pyrans and has a broad substrate scope (30 examples, up to 77% yield).

Ag2O-Induced Regioselective Huisgen Cycloaddition for the Synthesis of Fully Substituted Pyrazoles as Potential Anticancer Agents.

Efficient regioselective synthesis of novel fully substituted pyrazoles has been achieved through Huisgen cycloaddition reaction of δ-acetoxy allenoates with hydrazonoyl chlorides by the addition of Ag2O. The present approach offers the advantages of simpleness, high efficiency, mild conditions, wide substrate scope, and good-to-excellent regioselectivities. The strategy could be performed on a large-scale pattern to allow access to structurally versatile pyrazoles, of which a key intermediate of lonazolac (303), a nonsteroidal anti-inflammatory drug, could be synthesized efficiently. Moreover, several pyrazoles show obvious growth-inhibitory activity of Huh-7 cells, expected as potential anticancer agents.

Pyridine vs DABCO vs TBAB in Annulations of δ-Acetoxy Allenoates with Thioamides Leading to Dihydrothiophene, Thiopyran, and Thiazole Scaffolds.

The same δ-acetoxy allenoates and thioamides, under DABCO, pyridine, or tetra-n-butyl ammonium bromide (TBAB) catalysis, undergo distinctly different annulations giving chemoselective routes to dihydrothiophene, thiopyran, or thiazole motifs. Thus, using pyridine in [3 + 2] annulation, dihydrothiophenes are obtained as essentially single diastereomers. By contrast, under DABCO catalysis, allenoates deliver thiopyran motifs in good to high yields through 6-exo-dig cyclization. In the thiazole forming [3 + 2] annulation, tetra-n-butyl ammonium bromide (TBAB) facilitates addition-elimination and 5-exo-trig cyclization in which β- and γ-carbons of allenoates participate to deliver thiazole cores exclusively with a Z-isomeric exocyclic double bond. A possible rationale for these observations is delved into.

Stereo- and Regioselective [3+2] Cycloaddition of Acetoxy Allenoates with Azides: Metal-Free Synthesis of Multisubstituted Triazoles

AbstractWe have developed a regio- and stereoselective thermal [3+2]-cycloaddition protocol involving acetoxy allenoates as 1,2-dipoles under metal-free conditions for the synthesis of 1,4,5-tri/1,5-disubstituted 1,2,3-triazoles. δ-Acetoxy allenoates act as α- and β-carbon donors and lead to trisubstituted 1,2,3-triazoles with an alkenyl functionality at the 5-position. In sharp contrast to this, β- and γ-carbons participate in the case of β′-acetoxy allenoates to afford 1,5-disubstituted triazole cores. This [3+2] cycloaddition shows a broad substrate scope concerning acetoxy allenoate as well as azide and offers essentially E-stereoisomers in good to high yields. Divergently, the reaction of δ-acetoxy allenoate with trimethylsilyl azide gives an acyclic, nitrogen-inserted product with the cleavage of C–C bonds.

Divergent Reactivity of δ- and β'-Acetoxy Allenoates with 2-Sulfonamidoindoles via Phosphine Catalysis: Entry to Dihydro-α-carboline, α-Carboline, and Spiro-cyclopentene Motifs.

The reactivity of 2-sulfonamidoindoles with acetoxy allenoates under phosphine catalysis depends on the disposition of the acetoxy (OAc) group on the allenoate. In the temperature-controlled [3 + 3] annulations, δ-acetoxy allenoates afforded dihydrocarboline and carboline scaffolds with carbon-nitrogen nucleophilic 2-sulfonamidoindoles, in which allenoate serves as a β-, γ-, and δ-carbon donor. At room temperature (25 °C), dihydro-α-carboline motifs were obtained exclusively through Michael addition, 1,4-proton shift, isomerization, 1,2-proton transfer, phosphine elimination, and aza-Michael addition. The higher temperature (80 °C) cascade protocol using Ph3P-Cs2CO3 combination involves addition-elimination, aza-Claisen rearrangement, tosyl migration, and aromatization as key steps to give α-carbolines containing tosyl functionality at the γ-carbon. In contrast, with β'-acetoxy allenoate, 2-sulfonamidoindole acts only as a carbo-nucleophile in (p-tolyl)3P-directed [4 + 1] spiro-annulation, leading to five-membered spiro-carbocyclic motifs essentially as single diastereomers (dr >20:1) via chemoselective carbo-annulation.

Contrasting Carboannulation Involving δ-Acetoxy Allenoate as a Four-Carbon Synthon Using DABCO and DMAP: Access to Spiro-carbocyclic and m-Teraryl Scaffolds.

Spiro-annulation involving δ-acetoxy allenoate and alkyl benzoisothiazole dioxide (N-sulfonyl ketimine) triggered by DABCO/MeCO2H combination leads to an essentially single diastereomer via chemo- and regiospecific [4 + 2]-carboannulation and a new hydroxyl group is introduced. In contrast, DMAP-catalyzed benzannulation using the same reactants affords unsymmetrical m-teraryls via Mannich coupling, sequential proton transfers, and C-N bond cleavage. Here, δ-acetoxy allenoate serves as a 4C-synthon and the carboannulation is completely base dependent and mutually exclusive.

Lewis Base-Switched [3 + 3] and [4 + 2] Annulation Reactions of δ-Acetoxy Allenoates with Cyclic N-Sulfonyl Imines: Divergent Synthesis of Functionalized α-Pyridyl Acetates and Teraryl Scaffolds.

Under metal-free conditions, δ-acetoxy allenoates react with cyclic N-sulfonyl imines (sulfamidate imines/sulfonyl imines) to afford functionalized 2-pyridinyl acetates (α-pyridyl acetates) or teraryl motifs by a simple Lewis base switch. Thus, while DBU/Na2CO3 combination-directed [3 + 3] annulation involves sulfonyl elimination via O-S or C-S bond cleavage, affording 2-pyridinyl acetates, Ph3P-catalyzed [4 + 2] annulation leads to functionalized teraryls via Mannich coupling and C-N bond cleavage with retention or cleavage of the sulfamoyloxy group depending on the reaction conditions.

Access to Aryl-Naphthaquinone Atropisomers by Phosphine-Catalyzed Atroposelective (4+2) Annulations of δ-Acetoxy Allenoates with 2-Hydroxyquinone Derivatives.

Although asymmetric phosphine catalysis is a powerful tool for the construction of various chiral carbon centers, its synthetic potential toward an enantioenriched atropisomer has not been explored yet. Reported herein is a phosphine-catalyzed atroposelective (4+2) annulation of δ-acetoxy allenoates and 2-hydroxyquinone derivatives. The reaction provides expedient access to aryl-naphthaquinone atropisomers by the de novo construction of a benzene ring. The two functionalities of the catalyst, a tertiary phosphine (Lewis base) and a tertiary amine (Brønsted base), cooperatively enable this process with high regio- and enantioselectivities.

Phosphine-Promoted Divergent Annulations of δ-Acetoxy Allenoates with α-Hydroxy-β-carbonyl Ester Derivatives: Synthesis of Tetrasubstituted Cyclopentadienes and Benzenes.

The substrate-dependent annulations of δ-acetoxy allenoates with α-hydroxy-β-carbonyl ester derivatives are reported. 2-[(Methoxycarbonyl)oxy]malonate as a C1 partner is able to undergo (1 + 4) annulations with allenoates in the presence of a catalytic amount of phosphine, affording cyclopentadienes in good yields. However, (2 + 4) annulations of allenoates with 2-(tosyloxy)-3-ketoesters are instead observed with the assistance of stoichiometrical phosphine and base, leading to tetrasubstituted benzene products. In these two reactions, δ-acetoxy allenoate serves as a 1,4-disubstituted diene synthon.

Phosphine-Catalyzed (3 + 2) Annulation of δ-Acetoxy Allenoates with 2-Sulfonamidomalonate: Synthesis of Highly Substituted 3-Pyrrolines and Mechanistic Insight.

A mild and efficient synthetic protocol for 3-pyrrolines via the phosphine-catalyzed (3 + 2) annulation of δ-acetoxy allenoates with 2-sulfonamidomalonate is reported. The asymmetric version (up to 83% ee) is also achieved by using phosphine ( R)-SITCP as the catalyst. Mechanistic experiments disclose that the involved deprotonation of amide N-H and aza-addition to vinyl phosphonium might proceed in a concerted manner.

Facile Access to 1,5-Benzodiazepines via Amine-Promoted (4+3) Annulations of δ-Acetoxy Allenoates with o-Diaminobenzenes under Mild Conditions

An amine-promoted (4+3) annulation of δ-acetoxy allenoate with o-diaminobenzene is reported, providing a facile access to 1,5-benzodiazepine. This method features wide reaction scope, mild conditions, and readily available starting materials. The cascade reaction involves aza-Michael addition of o-diaminobenzene to allenoate, elimination of acetate group, and subsequent 1,6-aza-Michael addition.

Phosphine-catalysed α-umpolung addition of nucleophiles to δ-acetoxy allenoates: stereoselective synthesis of 2,4-dienoates.

The first example of phosphine-catalyzed α-umpolung addition of nucleophiles to allenoates is described, which features the use of δ-acetoxy allenoate to generate a 3-phosphonium-2,4-dienoate intermediate, thus facilitating the α-umpolung addition of nucleophiles. Both sulfinate and diarylphosphine oxide are competitive nucleophiles, affording highly activated conjugated dienes with good to excellent stereoselectivities.

Phosphine-Catalyzed Asymmetric (3+2) Annulations of δ-Acetoxy Allenoates with 2-Naphthols.

Phosphine-catalyzed (3+2) annulations of δ-acetoxy allenoates with 2-naphthols are reported, wherein the δC of allentoate reacts with the αC of 2-naphthol to form the C-C bond while a C-O bond is formed between the γC of allenoate and the hydroxyl group of 2-naphthol. When (R)-SITCP is used as the catalyst, 1,2-dihydronaphtho[2,1-b]furans are obtained in moderate to good yields and with high enantioselectivity. This method is useful for the construction of enantiomerically enriched atropoisomeric furans via a central to axial chirality conversion strategy.

Three-Component Synthesis of Benzopyrans from δ-Acetoxy Allenoates

Key words organocatalysis - [4+2] annulation - acetoxy allenoates - cyclization - benzopyrans

Construction of Complex 1,3-Cyclohexadienes via Phosphine-Catalyzed (4 + 2) Annulations of δ-Acetoxy Allenoates and Ketones.

The phosphine-catalyzed substrate-dependent (4 + 2) annulations of δ-acetoxy allenoates with ketones is described. Allenoates 1 with an alkyl substituent at δC are able to react with cyclic 1,3-diketones 2, wherein the δC is attacked by the methenyl carbon of 2 while the αC attacks the ketone of 2. Allenoates 5 with an aryl group at δC is poised to react with cyclic β-carbonyl amides 6, in which the αC is attacked by the methenyl carbon of 6 and the δC undergoes 1,2-addition to the ketone of 6.

Phosphine-Catalyzed Asymmetric (3 + 2) Annulations of δ-Acetoxy Allenoates with β-Carbonyl Amides: Enantioselective Synthesis of Spirocyclic β-Keto γ-Lactams.

While the phosphine catalysis is a powerful tool for the construction of N-heterocycles, the phosphine-catalyzed annulations toward lactam motif are still extremely scarce. Here, we report the asymmetric (3 + 2) annulations of δ-acetoxy allenoates with β-carbonyl amides by using the (R)-SITCP catalyst. The δC and γC of allenoate respectively engage in annulation with the αC and N of the amide, forging a γ-lactam with good to excellent stereoselectivity.