Allylation Of Ketones Research Articles

A simple and highly selective chalcone fluorescent chemical sensor for the detection of tryptophane

In this study, 1-ferrocenyl-3-(2-hydroxyphenyl) allyl ketone (probe A) was synthesized using a solvent-free method in conjunction with solid-phase grinding and employed as a probe for the detection of tryptophan (Trp). The probe exhibits selective recognition of Trp as evidenced by UV–Vis and fluorescence spectra. In complex scenarios, the probe’s recognition of Trp remains unaffected by both the presence of interfering substances and the duration of exposure. A pH range of 8 to 12 is found to be optimal for the detection of Trp. Job’s curve analysis revealed that the binding ratio between the probe and Trp is 1:1. Based on the Benesi-Hildebrand equation, the binding constant for the interaction between probe A and Trp is calculated to be 1.5 × 107 M−1. The detection limit for Trp was determined to be 9.55 × 10−5 M. The sensing mechanism of the probe for Trp was elucidated through 1H NMR and FT-IR analyses.

C‐C Bond Formation by Dual Pyrrolidine and Nickel Catalysis: Allylation of Ketones by Allylic Alcohols.

Whilst catalytic ketone allylation using palladium(0) is well–precedented, nickel(0)‐catalysed equivalents of such reactions remain scarce. We report here the first nickel‐catalysed allylation of ketones which uses an easily handled and inexpensive bench‐stable Ni(II) pre‐catalyst. This method avoids generation of stoichiometric by‐products via the use of readily available allyl alcohols, rather than the esters or related derivatives which are often used in such transformations. Under the optimised conditions, 25 monoallylated ketones were obtained in 16% to 98% yield and with high selectivity for the linear (E)–isomers.

Dynamic kinetic asymmetric allylation, propargylation and crotylation of ketones using copper catalysis

Dynamic kinetic asymmetric allylation, propargylation and crotylation of ketones using copper catalysis

Asymmetric Synthesis of Trisubstituted Vicinal Diols through Copper(I)‐Catalyzed Diastereoselective and Enantioselective Allylation of Ketones with Siloxypropadienes

AbstractChiral trisubstituted vicinal diols are a type of important organic compounds, serving as both common structure units in bioactive natural products and chiral auxiliaries in asymmetric synthesis. Herein, by using siloxypropadienes as the precursors of allyl copper(I) species, a copper(I)‐catalyzed diastereoselective and enantioselective reductive allylation of ketones was achieved, providing both syn‐diols and anti‐diols in good to excellent enantioselectivity. DFT calculations show that cis‐γ‐siloxy‐allyl copper species are generated favorably with either 1‐TBSO‐propadiene or 1‐TIPSO‐propadiene. Moreover, the steric difference of TBS group and TIPS group distinguishes the face selectivity of acetophenone, leading to syn‐selectivity for 1‐TBSO‐propadiene and anti‐selectivity for 1‐TIPSO‐propadiene. Easy transformations of the products were performed, demonstrating the synthetic utility of the present method. Moreover, one chiral diol prepared in the above transformations was used as a suitable organocatalyst for the catalytic asymmetric reductive self‐coupling of aldimines generated in situ with B2(neo)2.

Asymmetric Synthesis of Trisubstituted Vicinal Diols through Copper(I)-Catalyzed Diastereoselective and Enantioselective Allylation of Ketones with Siloxypropadienes.

Chiral trisubstituted vicinal diols are a type of important organic compounds, serving as both common structure units in bioactive natural products and chiral auxiliaries in asymmetric synthesis. Herein, by using siloxypropadienes as the precursors of allyl copper(I) species, a copper(I)-catalyzed diastereoselective and enantioselective reductive allylation of ketones was achieved, providing both syn-diols and anti-diols in good to excellent enantioselectivity. DFT calculations show that cis-γ-siloxy-allyl copper species are generated favorably with either 1-TBSO-propadiene or 1-TIPSO-propadiene. Moreover, the steric difference of TBS group and TIPS group distinguishes the face selectivity of acetophenone, leading to syn-selectivity for 1-TBSO-propadiene and anti-selectivity for 1-TIPSO-propadiene. Easy transformations of the products were performed, demonstrating the synthetic utility of the present method. Moreover, one chiral diol prepared in the above transformations was used as a suitable organocatalyst for the catalytic asymmetric reductive self-coupling of aldimines generated in situ with B2(neo)2.

Radical Addition-Enabled C-C σ-Bond Cleavage/Reconstruction to Access Functional Indanones: Total Synthesis of Carexane L.

C-C σ-bond cleavage and reconstruction is a significant tool for structural modification in synthetic chemistry but it remains a formidable challenge to perform on unstrained skeletons. Herein, we describe a radical addition-enabled C-C σ-bond cleavage/reconstruction reaction of unstrained allyl ketones to access various functional indanones bearing a benzylic quaternary center. The synthetic utility of this method has been showcased by the first total synthesis of carexane L, an indanone-based natural product.

Electrochemical allylation of aldehydes and ketones with allylic alcohols

We disclose herein an electrochemical allylation of unactivated aldehydes and ketones with allylic alcohols. Various homoallylic alcohols can be obtained by treatment of aldehydes/ketones with allyl alcohols in a simple undivided cell.

Copper-Catalyzed Umpolung Reactivity of Propargylic Carbonates in the Presence of Diboronates: One Stone Four Birds.

Allylation and propargylation are two powerful synthetic strategies for making new substances that have been of significant importance in chemistry, medicine, and material fields. Conventional tactics employ various preformed allylation and propargylation reagents. In this study, a conceptually novel copper-catalyzed and B2pin2-mediated Umpolung reactivity of propargylic carbonates has been achieved for the first time, realizing both allylation and propargylation of aldehydes and ketones without additional reductants. Three types of allylation products and one type of propargylation product are generated efficiently, and all allylation products are formed with syn-configurations predominantly. The choice of ligands plays a vital role in modulating the Umpolung modes. The synthetic applications have been demonstrated in a myriad of further transformations including natural product synthesis, and systematic mechanistic studies have been conducted to reveal detailed insights into the Umpolung processes.

Copper(I)-Catalyzed Asymmetric Allylation of Ketones with 2-Aza-1,4-Dienes.

Catalytic asymmetric allylation of ketones under proton-transfer conditions is a challenging issue due to the limited pronucleophiles and the electrophilic inertness of ketones. Herein, a copper(I)-catalyzed asymmetric allylation of ketones with 2-aza-1,4-dienes (N-allyl-1,1-diphenylmethanimines) is disclosed, which affords a series of functionalized homoallyl tertiary alcohols in high to excellent enantioselectivity. Interestingly, N-allyl-1,1-diphenylmethanimines work as synthetic equivalents of propanals. Upon the acidic workup, a formal asymmetric β-addition of propanals to ketones is achieved. An investigation on KIE effect indicates that the deprotonation of N-allyl-1,1-diphenylmethanimines is the rate-determining step, which generates nucleophilic allyl copper(I) species. Finally, the synthetic utility of the present method is demonstrated by the asymmetric synthesis of (R)-boivinianin A and (R)-gossonorol.

Copper(I)‐Catalyzed Asymmetric Allylation of Ketones with 2‐Aza‐1,4‐Dienes

AbstractCatalytic asymmetric allylation of ketones under proton‐transfer conditions is a challenging issue due to the limited pronucleophiles and the electrophilic inertness of ketones. Herein, a copper(I)‐catalyzed asymmetric allylation of ketones with 2‐aza‐1,4‐dienes (N‐allyl‐1,1‐diphenylmethanimines) is disclosed, which affords a series of functionalized homoallyl tertiary alcohols in high to excellent enantioselectivity. Interestingly, N‐allyl‐1,1‐diphenylmethanimines work as synthetic equivalents of propanals. Upon the acidic workup, a formal asymmetric β‐addition of propanals to ketones is achieved. An investigation on KIE effect indicates that the deprotonation of N‐allyl‐1,1‐diphenylmethanimines is the rate‐determining step, which generates nucleophilic allyl copper(I) species. Finally, the synthetic utility of the present method is demonstrated by the asymmetric synthesis of (R)‐boivinianin A and (R)‐gossonorol.

Defluorinative 1,3-Dienylation of Fluoroalkyl N-Triftosylhydrazones with Homoallenols.

A silver-catalyzed regioselective defluorinative 1,3-dienylation of trifluoromethyl phenyl N-triftosylhydrazones using homoallenols as 1,3-dienyl sources provides a variety of α-(di)fluoro-β-vinyl allyl ketones with excellent functional group tolerance in moderate to good yields. The reaction proceeds through a silver carbene-initiated sequential etherification and Claisen type [3,3]-sigmatropic rearrangement cascade. The synthetic utility of this protocol was demonstrated through the downstream synthetic elaboration toward diverse synthetically useful building blocks.

Copper‐Catalyzed Enantioselective and Regiodivergent Allylation of Ketones with Allenylsilanes

AbstractWe report herein a regiodivergent and enantioselective allyl addition to ketones with allenylsilanes through copper catalysis. With the combination of CuOAc, a Josiphos‐type bidentate phosphine ligand and PhSiH3, allyl addition to a variety of ketones furnishes branched products in excellent enantioselectivities. The regioselectivity is completely reversed by employing the P‐stereogenic ligand BenzP*, affording the linear products with excellent enantioselectivities and good Z‐selectivities. The linear Z‐product could be converted to E‐product via a catalytic geometric isomerization of the Z‐alkene group. The silyl group in the products could provide a handle for downstream elaboration.

Cobalt-Catalyzed Decarboxylative Allylations: Development and Mechanistic Studies.

In recent years, there has been a concerted drive to develop methods that are greener and more sustainable. Being an earth-abundant transition metal, cobalt offers an attractive substitute for commonly employed precious metal catalysts, though reactions engaging cobalt are still less developed. Herein, we report a method to achieve the decarboxylative allylation of nitrophenyl alkanes, nitroalkanes, and ketones employing cobalt. The reaction allows for the formation of various substituted allylated products in moderate-excellent yields with a broad scope. Additionally, the synthetic potential of the methodology is demonstrated by the transformation of products into versatile heterocyclic motifs. Mechanistic studies revealed an in situ activation of the Co(II)/dppBz precatalyst by the carboxylate salt to generate a Co(I)-species, which is presumed to be the active catalyst.

Organocatalytic Asymmetric Inverse-Electron-Demand Diels-Alder Reaction between Alkylidene Pyrazolones and Allyl Ketones: Access to Tetrahydropyrano[2,3-c]pyrazoles.

Herein we report a catalytic asymmetric inverse-electron-demand Diels-Alder reaction between alkylidene pyrazolones and allyl ketones. Allyl ketone gets activated by a bifunctional thiourea catalyst and acts as a dienolate in this reaction. The trisubstituted tetrahydropyrano[2,3-c]pyrazoles were obtained in moderate to good yields with high diastereo- and enantioselectivities. Few applications, including a decarbonylation reaction, have been demonstrated.

Visible-light-induced defluorinative allylation of difluoromethyl ketones using alkylamines as bifunctional agents

A visible-light-induced alkylamine-facilitated reductive defluoroallylation of difluoromethyl ketones with allylic chlorides is reported, enabling efficient access to α-fluoro alkenylketones with high efficiency.

Mechanistic Studies of Carbonyl Allylation Mediated by (NHC)CuH: Isoprene Insertion, Allylation, and β-Hydride Elimination.

The ability of Cu-H complexes to undergo selective insertion of unsaturated hydrocarbons under mild conditions has rendered them valuable, versatile catalysts. The direct formation of Cu allyl intermediates from unfunctionalized 1,3-dienes and transient Cu hydrides is an appealing strategy for upgrading conjugated diene feedstocks. However, empirical mechanistic studies of the underlying elementary steps and characterization of key intermediates in Cu-H catalysis are sparse. Using [(NHC)CuH]2 (NHC = N-heterocyclic carbene), we examined the steric effects of NHC ligands on two key elementary steps of CuH-catalyzed carbonyl allylation: the insertion of a diene into the Cu-H bond to produce a Cu-allyl complex, and the formation of C-C bonds from stoichiometric allylations of ketones and aldehydes. The resulting allyl and homoallylic alkoxide complexes have been characterized by NMR spectroscopy and single-crystal X-ray diffraction. Employing isolable (NHC)Cu-allyl complexes, we further evaluated the roles of the ligand size, electronic properties of carbonyl substrates, coordinating groups within the substrate, and solvent on the regioselectivity, diastereoselectivity, and relative rate of the C-C bond formation step. In contrast to the clean allylation of ketones, allylation of aldehydes provided a rare example of a formal β-hydride elimination reaction from a secondary homoallylic alkoxide species. Mechanistic studies of key elementary steps provide insights for a range of catalytic reactions of dienes mediated by hydride complexes.

One-Pot Enol Silane Formation–Allylation of Ketones Promoted by Trimethylsilyl Trifluoromethanesulfonate

AbstractKetones and related substrate classes undergo enol silane formation in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine, reaction conditions that also promote the in situ ionization of allyl propionates. When these two processes are performed in one pot, allylation of the ketone is observed in high yields. Aldehydes, esters, and thioesters also serve as enol silane precursors under these conditions. When unsymmetrical allyl cations are employed, regioselectivity depends upon the electronic and steric properties of the substituents.

Rhodium-Catalyzed Regio- and Enantioselective Direct Allylation of Methyl Ketones

AbstractWe report a highly branch-selective and enantioselective allylic alkylation of simple ketones with racemic aliphatic allylic carbonates under mild conditions. By using a Rh–bisoxazolinephosphine system and catalytic amounts of a base in THF, a series of chiral β-branched γ,δ-unsaturated ketones were obtained with excellent regio- and enantioselectivities. An outer-sphere nucleophilic substitution C–C bond-formation process is proposed on the basis of mechanistic studies.

Synthesis of Pyrrole via Formal Cycloaddition of Allyl Ketone and Amine under Metal-Free Conditions.

A new metal-free synthesis of pyrrole from allyl ketone and amine has been established. The reaction proceeds via an thiolative activation of the C-C double bond with dimethyl(methylthio)sulfonium trifluoromethanesulfonate, followed by a nucleophilic ring-opening addition of primary amine to the generated episulfonium intermediate, and then an internal condensation and aromatization. This mild procedure provides a novel strategy to the construction of substituted pyrroles through a formal [4 + 1] cycloaddition reaction.

Boron-Catalyzed, Diastereo- and Enantioselective Allylation of Ketones with Allenes.

The diastereo- and enantioselective allylation of ketones remains a synthetic challenge, with transition metal catalysis offering the most applied methods. Here, a boron-catalyzed allylation of ketones with allenes is presented. Excellent yield, regioselectivity, and diastereoselectivity were found across functionalized substrates. The reaction was further developed to accommodate an enantioenriched boron catalyst and thus gave asymmetric ketone allylation in good yield, diastereoselectivity, and enantioselectivity. Mechanistic studies supported a hydroboration–allylation–transborylation pathway.