Propargylic Carbonates Research Articles

One‐pot carboxylative cyclization of propargylic alcohols and CO2 catalysed by N‐heterocyclic carbene/Ag systems

A series of N‐heterocyclic carbene (NHC)/Ag systems were developed for the carboxylative assembly of propargylic alcohols and carbon dioxide (CO2). With the catalysis of these catalytic systems, a variety of target α‐alkylidene cyclic carbonates could be obtained smoothly under atmospheric CO2 pressure in straightforward one‐pot processes. Particularly, these reactions could be performed without any stoichiometric addition of bases or additives. Further mechanistic investigation reveals that the excellent activities are attributed to the effective activations of CO2 accomplished by the NHCs via the formation of the NHC‐CO2 adducts.

One–pot Selective Synthesis of 2,3‐Dihydro‐4H‐Furo[3,2‐c]coumarins by Palladium‐Catalyzed Silver‐Assisted Propargylation/Intramolecular 5‐exo–dig Cyclization

AbstractA new catalytic system using bis(triphenylphosphine)palladium(II) dichloride and Ag2CO3 was developed for the one‐pot selective synthesis of dihydrofuro[3,2‐c]coumarin 3 from 4‐hydroxycoumarin (1) and propargylic carbonate 2 under the mild condition. Our catalytic system afforded distinct regioselectivity compared to reported methodologies using palladium catalysts, 2 and active methylene compounds. In addition, furo[3,2‐c]coumarin 4 was derived from 3 with Et3N. The proposed reaction mechanism involved 4‐hydroxycoumarin (1) reacting with the η1–(propargyl)palladium complex to generate a terminal alkyne, and subsequent intramolecular 5‐exo‐dig cyclization selectively synthesized 3 in one‐pot. The newly developed methodology is beneficial in the construction of a novel compound library related to furocoumarins with distinct regioselective preference.

Manganese(I)-Catalyzed Regioselective C-H Allenylation: Direct Access to 2-Allenylindoles.

A MnI -catalyzed regioselective C-H allenylation is reported that allows a broad range of 2-allenylindoles to be synthesized regioselectively on a gram scale under simple conditions. Notably, a highly efficient chirality transfer was observed (up to 93 % ee) in this transformation. This procedure was further found to allow, for the first time, the direct preparation of ketones by MnI -catalyzed C-H activation. Mechanistic investigations revealed that the precoordination of the oxygen atom to the manganese center as well as the congested tertiary carbon atom in the propargylic carbonates play a crucial role.

Silver(I)-Promoted Cascade Reaction of Propargylic Alcohols, Carbon Dioxide, and Vicinal Diols: Thermodynamically Favorable Route to Cyclic Carbonates.

A silver(I)-promoted cascade reaction was developed for the synthesis of cyclic carbonates from terminal propargylic alcohols, carbon dioxide, and vicinal diols. Compared with direct condensation of vicinal diols with CO2, this protocol provides a thermodynamically favorable route to cyclic carbonates and α-hydroxyl ketones in excellent yields (up to 97%) without the additional dehydration step. Such a cascade procedure proceeds presumably through initial reaction of propargylic alcohol with CO2 and subsequent nucleophilic attack of vicinal alcohol on in situ-formed α-alkylidene cyclic carbonate, resulting in successive generation of α-alkylidene cyclic carbonate, unsymmetrical β-oxoalkyl carbonate, cyclic carbonate, and α-hydroxyl ketone.

A simple and robust AgI/KOAc catalytic system for the carboxylative assembly of propargyl alcohols and carbon dioxide at atmospheric pressure

A simple, robust and economical AgI/KOAc system was developed for the carboxylative assembly of propargyl alcohols and CO2 under mild conditions applying an unprecedentedly low level of 0.05 mol% Ag loading.

Palladium-Catalyzed Three-Component Reaction of Propargyl Carbonates, Isocyanides, and Alcohols or Water: Switchable Synthesis of Pyrroles and Its Bicyclic Analogues.

In the presence of a catalytic amount of Pd(OAc)2 and a stoichiometric amount of tert-butylamine, the reaction of propargyl carbonates, isocyanides, and alcohols afforded polysubstituted aminopyrroles in good yields. Using water as a nucleophile instead of alcohol, the same reaction provided 1,4-dihydro-6H-furo[3,4-b]pyrrol-6-imines. A triple isocyanide insertion to the hypothetic (σ-allenyl)palladium(II) intermediate was involved in these ABC3-type multicomponent reactions. The key role of tert-butylamine was accounted for by its reaction with in situ generated carbon dioxide to form the carbamic acid, which in turn served as a nucleophile to trap the nitrilium intermediate.

Experimental and Kinetic Modeling Study of 2-Methylfuran Pyrolysis at Low and Atmospheric Pressures

The pyrolysis of 2-methylfuran (MF) was studied from 900 to 1530 K in a flow reactor at 30 and 760 Torr. Synchrotron vacuum ultraviolet photoionization mass spectrometry and gas chromatography were used for identification and mole fraction measurements of pyrolysis products, especially free radicals and aromatics. Specific products were observed for the two main unimolecular decomposition pathways of MF, such as propargyl radical, methyl radical, 1-butyne, and carbon monoxide. A previous kinetic model of MF was updated on the basis of recent theoretical and modeling progresses, especially for the aromatic formation sub-mechanism. The updated model was validated by the new pyrolysis data. Kinetic analyses including rate of production analysis, and sensitivity analysis were used to provide insight into the pyrolysis chemistry of MF, especially the decomposition of MF and aromatic formation. The pyrolysis of MF was found with the kinetic characteristics of both furan pyrolysis and 2,5-dimethylfuran (DMF) pyr...

Palladium-Catalyzed Multicomponent Reaction (MCR) of Propargylic Carbonates with Isocyanides.

A palladium-catalyzed multicomponent reaction (MCR) of propargylic carbonates with isocyanides is reported. Remarkably, the orderly insertion of isocyanides affords two types of valuable N-heterocyclic products (Z)-6-imino-4,6-dihydro-1H-furo[3,4-b]pyrrol-2-amines and (E)-5-iminopyrrolones in high yields. Systematic analysis of the reaction conditions indicates that the selectivity of these N-heterocyclic products can be controlled by ligands and temperature.

Gold(I)-Induced Rearrangements of Propargyl Derivatives: A Gas-Phase Study

The gold(I)-induced rearrangements of a variety of propargyl derivatives (ethers, acetals, acetates, and carbonates) were explored in the gas phase with experiments in an ion-trap mass spectrometer as well as with computations at the M06/QZVP level. In accord with condensed-phase studies, it appears that propargyl ethers and acetals prefer 1,3-migrations to give allenes with the release of aldehydes. With propargyl acetates, we show that the preferred path is also a 1,3-migration of the acetate to give an allene species, but that a 1,2-migration to give a gold(I) carbene species is competitive. However, with the kinetic window of our gas-phase instrumentation, only systems that can be locked into a gold(I) carbene structure give carbenoid chemistry. Finally, we found that propargyl carbonates react with gold(I) species and release CO2 in the gas phase; the likely pathway involves sequential 1,3-migrations, leading to a propargyl ether. Overall, the results highlight the dynamic nature of gold(I)-induced r...

Palladium-Catalyzed Regiodivergent Substitution of Propargylic Carbonates.

The palladium(0)-catalyzed, ligand-controlled, regioselective addition of diaryl acetonitrile pronucleophiles to propargylic carbonates is reported. Selective formation of either terminal 1,3-dienyl or propargylated products is proposed to arise from a change in reaction mechanism controlled by the denticity of the coordinating ligand.

Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation.

Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C–C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility.

Gold-Catalyzed Cyclization of Furan-Ynes bearing a Propargyl Carbonate Group: Intramolecular Diels-Alder Reaction with In Situ Generated Allenes.

Gold-catalyzed cyclization of various furan-ynes with a propargyl carbonate or ester moiety results in the formation of a series of polycyclic aromatic ring systems. The reactions can be rationalized through a tandem gold-catalyzed 3,3-rearrangement of the propargyl carboxylate moiety in furan-yne substrates to form an allenic intermediate, which is followed by an intramolecular Diels-Alder reaction of furan and subsequent ring-opening of the oxa-bridged cycloadduct. It was found that the steric and electronic properties of phosphine ligands on the gold catalyst had a significant impact on the reaction outcome. In the case of 1,5-furan-yne, the cleavage of the oxa-bridge in the cycloadduct with concomitant 1,2-migration of the R(1) group occurs to furnish anthracen-1(2H)-ones bearing a quaternary carbon center. For 1,4-furan-yne, a facile aromatization of the cycloadduct takes place to give 9-oxygenated anthracene derivatives.

ChemInform Abstract: Robust Silver(I) Catalyst for the Carboxylative Cyclization of Propargylic Alcohols with Carbon Dioxide under Ambient Conditions.

Inspired by the bulkier bis(triphenylphosphine)–silver cation-induced mechanism of propargylic alcohols and carbon dioxide through the alkyl carbonate intermediate, a robust dual-component catalytic system consisting of silver acetate and tetraheptylammonium bromide was rationally developed for the synthesis of α-methylene cyclic carbonates under ambient conditions without employing any additional organic base and ligand. This is one of the most effective catalysts reported to date for this conversion, with a very high turnover number of up to 6024, probably due to the synergistic effect of Lewis basic and Lewis acidic species for the activation of both propargylic alcohol and carbon dioxide by the formation of the alkyl carbonate with a bulkier counterion. Notably, this catalyst also worked well for the carboxylative cyclization of propargylic amines with carbon dioxide with the highest turnover number of 544.

Synthesis of Spirocyclic and Fused Cyclic Compounds by Transition-Metal-Catalyzed Intramolecular Friedel–Crafts-Type Reactions of Phenol Derivatives

This account describes the development of novel dearomatization reactions of phenols using transition-metal-catalyzed ipso-Friedel–Crafts-type processes. In general, phenols function as O-nucleo­philes in transition-metal-catalyzed allylic substitution reactions, providing the corresponding aryl ethers. We found that, however, an intramolecular ipso-Friedel–Crafts allylic alkylation of phenols proceeded smoothly in the presence of a palladium catalyst, producing various spiro[4.5]cyclohexadienone derivatives. This finding led us to launch detailed investigations into this type of reaction. Pd-catalyzed intramolecular Friedel–Crafts allylic alkylation of phenols was next examined to synthesize 10-vinyl 9,10-dihydrophenanthrene derivatives. This reaction was successfully extended to a catalytic asymmetric process. We also developed a novel synthetic method for spiro[5.5]cyclohexadienones based on a Pd-catalyzed intramolecular ipso-Friedel–Crafts-type addition of phenols to η3-propargylpalladium(II) intermediates. Mechanistic studies revealed that the present reaction proceeds through a rearomatization-assisted oxidative addition. Moreover, a Au-catalyzed intramolecular ipso-Friedel–Crafts alkenylation of phenols with a terminal alkyne is discussed. 1 Introduction 2 Pd-Catalyzed Intramolecular Friedel–Crafts Allylic Alkylation of Phenols 2.1 Synthesis of Spirocyclohexadienone Derivatives by Pd-Catalyzed Intramolecular ipso-Friedel–Crafts Allylic Alkylation of Phenols 2.2 Mechanistic Considerations 2.3 Application to Cascade Reaction Processes 2.4 Asymmetric Synthesis of Dihydrophenanthrene Derivatives by Pd-Catalyzed Asymmetric Intramolecular Friedel–Crafts Allylic Alkylation of Phenols 3 Dearomatization of Phenols by Activation of Propargyl Carbonates with a Pd Catalyst 4 Au-Catalyzed Intramolecular ipso-Friedel–Crafts Alkenylation of Phenols 5 Summary and Outlook

ChemInform Abstract: Palladium‐Catalyzed Modular Synthesis of Substituted Piperazines and Related Nitrogen Heterocycles.

AbstractThis novel method for the synthesis of substituted piperazine‐and piperazinone‐type compounds proceeds by a palladium‐catalyzed decarboxylative cyclization of propargyl carbonates with bis‐nitrogen nucleophiles with good functional group tolerance.

ChemInform Abstract: Synthesis of Allenes by Catalytic Coupling of Propargyl Carbonates with Aryl Iodides in the Presence of Diboron Species.

Bimetallic copper-/palladium-catalyzed multicomponent reaction of propargyl carbonates, aryl iodides, and diboron species was studied. This procedure can be used for synthesis of di-, tri-, and tetra-substituted allenes. Using diboronic acid, the reaction is supposed to proceed via allenylboronic acid intermediate.

ChemInform Abstract: Silver‐Catalyzed Three‐Component Reaction of Propargylic Amines, Carbon Dioxide, and N‐Iodosuccinimide for Stereoselective Preparation of (E)‐Iodovinyloxazolidinones.

The stereoselective synthesis of (E)-bromovinyloxazolidinones was developed by the three-component reaction of propargylic amines, carbon dioxide, and N-bromosuccinimide in the presence of a silver...

ChemInform Abstract: Cascade Synthesis of 3‐Alkylidene Dihydrobenzofuran Derivatives via Rhodium(III)‐Catalyzed Redox‐Neutral C—H Functionalization/Cyclization.

AbstractThe scalable reaction of substituted N‐phenoxyacetamides with 3‐aryl, hetaryl, and alkyl substituted propargyl carbonates furnishes 3‐alkylidene dihydrobenzofuran derivatives in moderate to high yields.

Platinum-Catalyzed Friedel-Crafts-Type C-H Coupling-Allylic Amination Cascade to Synthesize 3,4-Fused Tricyclic Indoles.

A novel platinum-catalyzed cascade cyclization reaction was developed by intramolecular Friedel-Crafts-type C-H coupling of aniline derivatives with a propargyl carbonate unit-allylic amination sequence. Treatment of various propargyl carbonates tethered to meta-aniline derivatives with a Pt(dba)3/DPEphos catalyst system afforded the corresponding 3,4-fused tricyclic 3-alkylidene indolines in 42-99% yield, which were transformed into 3,4-fused indole derivatives by reaction with trifluoroacetic acid. The reaction products exhibited antiproliferative activities against cancer cells, but not normal cells, revealing the potential usefulness of this reaction for medicinal chemistry.

Palladium Tandem Catalysis in the Atropodiastereoselective Synthesis of Indenes Bearing Central and Axial Chirality

The conversion of propargylic carbonates into allenes via Pd-catalyzed coupling with arylboronic acids, followed by tandem intramolecular Alder-ene cyclization, proceeds with remote diastereocontrol in the formation of indenes possessing two stereogenic elements (stereocenter and chiral axis). Highly configurationally stable atropisomers have been obtained with dr values up to >98:2. The reaction tolerates a range of commercially available functionalized arylboronic acids and allows the creation of C(sp2)–C(sp2) and C(sp2)–C(sp3) bonds in a single operation. Control experiments suggest that synergetic thermal and Pd-catalyzed cyclizations are likely to be involved in the second elementary step.