Vicinal Tricarbonyl Compounds Research Articles

Diethyl Mesoxalate, A Representative Tricarbonyl Compound – A Useful Synthetic Tool Possessing Diverse Reactivities

AbstractDiethyl mesoxalate, a vicinal tricarbonyl compound, possesses multiple functionalities that facilitate diverse chemical conversions. The central carbonyl group with two ester functionalities exhibits high electrophilicity to accept nucleophilic attacks of various reagents. This unusual electrophilicity enables the reaction with acid amides that are not common nucleophiles in organic syntheses. Condensation with active methylene compounds or amines leads to electron‐deficient alkenes and imines, respectively, which can be transformed into more complex polyfunctionalized compounds by a second nucleophilic addition. Chemical transformations between the central and adjacent ester carbonyls furnish new ring systems that are useful in material and pharmaceutical sciences. The central carbonyl group can also be built into a ring system by reacting with reagents possessing nucleophilic and electrophilic sites. Furthermore, the central carbonyl serves as a dienophile that undergoes cycloaddition to form functionalized heterocyclic compounds in a single step.

B(C6F5)3-Catalyzed Multicomponent Reactions of 2,3-Diketoesters, Amines, Allenes, and Nucleophiles: Synthesis of 2α-Functionalized Pyrroles.

An efficient B(C6F5)3-catalyzed multicomponent reaction of 2,3-diketoesters, amines, allenes, and nucleophiles was reported, which afforded 2α-functionalized pyrroles in moderate to good yields. The reaction features low catalyst loading, usage of a small amount of solvent, high atom economy, tunable installation of diverse functional groups at 2α-position, and water being formed as the byproduct. This is the first multicomponent reaction that combines vicinal tricarbonyl compounds with allenes.

Facile synthesis of 5α-functionalized pyrroles via multicomponent reactions of vicinal tricarbonyl compounds, enamines, and nucleophiles

A simple and general strategy was developed for the efficient synthesis of diverse flexible variant α-functionalized pyrrole derivatives.

Asymmetric Construction of α,α‐Disubstituted Piperazinones Enabled by Benzilic Amide Rearrangement

AbstractAn unprecedent asymmetric catalytic benzilic amide rearrangement for the synthesis of α,α‐disubstituted piperazinones is reported. The reaction proceeds via a domino [4+1] imidazolidination/formal 1,2‐nitrogen shift/1,2‐aryl or alkyl migration sequence, employing readily available vicinal tricarbonyl compounds and 1,2‐diamines as starting materials. This approach provides an efficient access to chiral C3‐disubsituted piperazin‐2‐ones with high enantiocontrol, which are exceedingly difficult to access from the existing synthetic methodologies. The observed enantioselectivity was proposed to be controlled by dynamic kinetic resolution in the 1,2‐aryl/alkyl migration step. The resulting densely functionalized products are versatile building blocks to bioactive natural products, drug molecules and their analogues.

Asymmetric Construction of α,α-Disubstituted Piperazinones Enabled by Benzilic Amide Rearrangement.

An unprecedent asymmetric catalytic benzilic amide rearrangement for the synthesis of α,α-disubstitutedpiperazinones is reported. The reaction proceeds via a domino [4+1] imidazolidination/formal 1,2-nitrogen shift/1,2-aryl or alkyl migration sequence, employing readily available vicinal tricarbonyl compounds and 1,2-diamines as starting materials. This approach provides an efficient access to chiral C3-disubsituted piperazin-2-ones with high enantiocontrol, which are exceedingly difficult to access from the existing synthetic methodologies. The observed enantioselectivity was proposed to be controlled by dynamic kinetic resolution in the 1,2-aryl/alkyl migration step. The resulting densely functionalized products are versatile building blocks to bioactive natural products, drug molecules and their analogues.

Permanganate oxidation of α,β-unsaturated carbonyls to vicinal tricarbonyls

An expedient synthesis of vicinal tricarbonyl compounds from α,β-unsaturated carbonyls through permanganate oxidation is reported. The key to this process is the presence of acetic acid additive, which enhances the oxidation ability of permanganate.

Rhodium-catalyzed aerobic conversion of 2-diazo-1,3-dicarbonyls to vicinal tricarbonyl compounds and their in-situ stability toward oxidative degradation

Several types of 2-diazo-1,3-dicarbonyl compounds (3), including α-diazo-β-ketoesters, 2-diazo-1,3-diketones and diazomalonates, are converted into the corresponding vicinal tricarbonyls (VTCs) (4) upon exposure to Rh2(OAc)4 catalyst and oxygen gas. The transformation is proposed to occur through the aerobic oxygenation of the rhodium carbenoid intermediate, facilitated by the suppression of a Wolff rearrangement via weak interaction with the substrate carbonyl group (ROC=O or RC=O). The reactions of α-diazo-β-ketoesters and 2-diazo-1,3-diketones give the desirable α,β-diketoesters and vic-triketones in 27-78% isolated yields, along with carboxylic acids and/or 2-oxoacids generated by in-situ oxidative C-C single bond cleavage of the former products. Moreover, the bond cleavage process is completely inhibited when the reactions are performed with diazomalonates, leading to the good to excellent formation of oxomalonates (up to 92% yield).

Synthesis of polymers containing vicinal tricarbonyl moiety and construction of reversible crosslinking–decrosslinking polymer system

AbstractVicinal tricarbonyl compounds, in which three carbonyl groups are consecutively connected, are intriguing reactive molecules with a highly electrophilic nature. The center carbonyl group activated by two adjacent electron‐withdrawing carbonyl groups reacts efficiently with weak nucleophiles such as water, alcohols, thiols and aromatic amines to afford the corresponding adducts. In addition, because the reactions of the center carbonyl group with nucleophiles are intrinsically in equilibrium, the adducts undergo dissociation into the corresponding tricarbonyl compounds and nucleophiles under the appropriate conditions. Based on the reversible nature of vicinal tricarbonyl compounds with nucleophiles, a reversible crosslinking–decrosslinking system can be constructed where appropriately designed polymers and crosslinkers bearing vicinal tricarbonyl compounds are effectively used. © 2021 Society of Chemical Industry

Convergent Synthesis of Dihydropyrans from Catalytic Three-Component Reactions of Vinylcyclopropanes, Diazoesters, and Diphenyl Sulfoxide.

A novel Rh(I)/La(III) cocatalytic three-component reaction of vinylcyclopropanes, diazoesters, and diphenyl sulfoxide has been developed. The reaction gives polysubstituted dihydropyrans as the reaction products. Mechanistic studies indicate that isomerization of vinylcyclopropanes gives conjugated dienes, which then undergo [4 + 2]-cycloaddition with vicinal tricarbonyl compounds generated by oxygen atom transfer from diphenyl sulfoxide to diazoesters.

Practical Approach for the Preparation of α-Keto Amides by Direct Aminocarbonylation of Carboxylic Esters with a Carbamoylsilane

A novel and practical method has been developed for the preparation of α-keto amides by a catalyst-free aminocarbonylation of carboxylic esters with N,N-dimethylcarbamoyl(trimethyl)silane under neutral conditions. A new protocol for the synthesis of vicinal tricarbonyl compounds was also developed by using this method. In the case of diesters, only one ester group reacted selectively with 1.2 equivalents of the carbamoylsilane, leading to the formation of a single α-keto amide. The reaction was suitable for aryl, hetaryl, or open-chain esters containing strongly electron-withdrawing groups.

Preparation of Biscarbonylmethylenetriphenylphosphorane Derivatives: A Mini-Review

Biscarbonylmethylenetriphenylphosphoranes are versatile compounds derived from stabilized α-carbonylmethylenetriphenylphosphoranes, mainly prepared by transylidation or by analogue methodologies; other procedures include electrochemical oxidation, palladium-catalized insertions and displacements reactions with tellurol esters, as well as the use of Bestmann’s ylide with different reagents and reaction conditions. These biscarbonylmethylenetriphenylphosphoranes are usually converted into acetylenes by thermal treatments. Biscarbonylmethylenetriphenylphosphoranes and their oxidation products -vicinal tricarbonyl compounds- are of high importance due to their use as synthons of more complex molecules and their promising biological activity.

Gold(I)-Catalyzed Oxidation of Acyl Acetylenes to Vicinal Tricarbonyls.

Efficient gold(I)-catalyzed oxidation of COR2-functionalized internal alkynes to vicinal tricarbonyl compounds by 2,6-dichloropyridine N-oxide proceeds under mild conditions (DCM, rt). This catalytic reaction provides a good to excellent yielding route to diverse tricarbonyls such as α,β-diketoesters, 1,2,3-triketones, and α,β-diketoamides. The utility of these compounds was also demonstrated by facile one-pot synthesis of important azaheterocyclic systems.

Unsymmetrical Tetra-Acceptor-Substituted Alkenes as Polyfunctionalized Building Blocks: A Divergent Synthesis of Densely Functionalized Pyrrolizines

Abstract Various tetra-acceptor-substituted alkenes possessing unsymmetrical substituents have been effectively synthesized from vicinal tricarbonyl compounds. The alkenes have polyfunctionality and high electron deficiency. In addition, they easily react with pyrroles to give divergent pyrrolizine derivatives via the conjugate addition of pyrroles followed by intramolecular cyclization. We successfully controlled the chemoselectivity of the intramolecular cyclization (ester/ketone attack) to afford a wide range of valuable pyrrolizine derivatives.

ChemInform Abstract: Reversible Capture and Release of Aromatic Amines by Vicinal Tricarbonyl Compound.

Abstract In this paper, we report reversible capture and release of aromatic amines by diphenylpropanetrione (DPPT). Addition of aromatic amines to the central carbonyl group occurred readily at ambient temperature to provide the aromatic amine adducts of DPPT (DPPT–aromatic amines), which has a hemiaminal structure. On the other hand, washing a solution of DPPT–aromatic amine with diluted hydrochloric acid (HCl) enabled successful recovery of DPPT to demonstrate the reversible nature of this system.

Vicinal Tricarbonyl Compounds: Versatile Building Blocks for Natural Product Synthesis

Due to their high density of functional groups, vicinal tri­carbonyl compounds are versatile building blocks for the synthesis of complex target molecules. Methods for their preparation and their use in stereoselective C–C bond formations, as well as for the synthesis of heteroaromatics, are summarised for the period 2006–2016. Several examples for their applications in natural product synthesis (awajanomycin, cladoniamide, wailupemycin) are presented. 1 Introduction 2 Preparation of Vicinal Tricarbonyl Compounds 3 Use in Stereoselective C–C Bond Formations 4 Use for the Synthesis of Heteroaromatics 5 Examples from Natural Product Synthesis 6 Conclusion

Hemithioketal formation of vicinal tricarbonyl compound with thiols and their recovery

In this paper, we report hemithioketal formation of diphenylpropanetrione (DPPT) with thiols and their recovery. Addition of thiols to the central carbonyl group occurred readily at ambient temperature to provide the thiol adducts of DPPT (DPPT–thiols), which has a hemithioketal structure. On the other hand, oxidizing DPPT–thiols with an oxidation reagent enabled successful recovery of DPPT, which indicated the reversible nature of this system.

Reversible capture and release of aromatic amines by vicinal tricarbonyl compound

In this paper, we report reversible capture and release of aromatic amines by diphenylpropanetrione (DPPT). Addition of aromatic amines to the central carbonyl group occurred readily at ambient temperature to provide the aromatic amine adducts of DPPT (DPPT–aromatic amines), which has a hemiaminal structure. On the other hand, washing a solution of DPPT–aromatic amine with diluted hydrochloric acid (HCl) enabled successful recovery of DPPT to demonstrate the reversible nature of this system.

ChemInform Abstract: Friedel—Crafts Reaction of Indoles with Vicinal Tricarbonyl Compounds Generated in situ from 1,3‐Dicarbonyl Compounds and TEMPO: Highly Selective Synthesis of Tertiary Alcohols.

A novel Friedel–Crafts reaction of indoles with vicinal tricarbonyl compounds generated in situ from 1,3-dicarbonyl compounds, which produces indole substituted tertiary alcohols in good to excellent yields and with good functional group tolerance, has been developed. The mechanistic pathway for this process involves the initial disproportionation of TEMPO, α-oxyamination of the 1,3-dicarbonyl compound followed by N–O bond cleavage to form the tricarbonyl intermediate. Addition of indole to this intermediate then generates the tertiary alcohol product. This method can also be used for the synthesis of pyrrole-containing tertiary alcohols. Further efforts aimed at elucidating the mechanism of the reaction and boardening the substrate scope of this process are ongoing.

Lanthanide-Catalyzed Oxyfunctionalization of 1,3-Diketones, Acetoacetic Esters, And Malonates by Oxidative C-O Coupling with Malonyl Peroxides.

The lanthanide-catalyzed oxidative C-O coupling of 1,3-dicarbonyl compounds with diacyl peroxides, specifically the cyclic malonyl peroxides, has been developed. An important feature of this new reaction concerns the advantageous role of the peroxide acting both as oxidant and reagent for C-O coupling. It is shown that lanthanide salts may be used in combination with peroxides for selective oxidative transformations. The vast range of lanthanide salts (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Y) catalyzes oxidative C-O coupling much more efficiently than other used Lewis and Bronsted acids. This oxidative cross-coupling protocol furnishes mono and double C-O coupling products chemo-selectively in high yields with a broad substrate scope. The double C-O coupling products may be hydrolyzed to vicinal tricarbonyl compounds, which are otherwise cumbersome to prepare. Based on the present experimental results, a nucleophilic substitution mechanism is proposed for the C-O coupling process in which the lanthanide metal ion serves as Lewis acid to activate the enol of the 1,3-dicarbonyl substrate. The side reactions-chlorination and hydroxylation of the 1,3-dicarbonyl partners-may be minimized under proper conditions.

Iodosobenzene-mediated direct and efficient oxidation of β-dicarbonyls to vicinal tricarbonyls catalyzed by iron(iii) salts

The direct and efficient oxidation of β-dicarbonyls to vicinal tricarbonyl compounds has been achieved, which was mediated by PhIO and catalyzed by Fe(NO3)3·9H2O under mild and environmentally friendly conditions.