Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles

A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E(+) = PhSe(+)) and 2-alkynyl ketones (E(+) = F(+), Cl(+), active halides) as the final products, respectively.     

The synthesis and natural distribution of the major ketone constituents in Echinacea pallida

The first synthesis of a series of ketones naturally occurring in E. pallida is described. The natural distribution of these ketones among different Echinacea species is also reported.     

A novel pyrrolidine imide catalyzed direct formation of alpha,beta-unsaturated ketones from unmodified ketones and aldehydes

A method for direct, stereoselective preparation of (E)-alpha,beta-unsaturated ketones from ketones and aldehydes, promoted by a novel pyrrolidine imide organocatalyst, has been developed in moderate to high yields. Unlike the Claisen-Schmidt condensation and Lewis acid catalyzed tandem aldol-dehydration processes, this method provides mild reaction conditions to access alpha,beta-unsaturated ketones from simple, unmodified ketones. [reaction: see text]     

Organocatalytic C3-selective Friedel-Crafts alkylations of indoles with alpha,beta-unsaturated ketones

The use of an equimolar amount of pyrrolidine and HClO4 (30 mol%) was found to be effective in promoting the conjugate addition of indoles to (E)-alpha,beta-unsaturated ketones, affording the corresponding beta-indolyl ketones in excellent yields.     

Stereoselective bioreduction of bulky-bulky ketones by a novel ADH from Ralstonia sp

Ketones with two bulky substituents, named bulky-bulky ketones, as well as less sterically demanding ketones were successfully reduced to the corresponding optically highly enriched alcohols using a novel identified recombinant short-chain alcohol dehydrogenase RasADH from Ralstonia sp. DSM 6428 overexpressed in E. coli.     

Transition-Metal-Free Superbase-Promoted Stereoselective α-Vinylation of Ketones with Arylacetylenes: A General Strategy for Synthesis of β,γ-Unsaturated Ketones

A wide variety of β,γ-unsaturated ketones of E configuration have been obtained in good to excellent yields via KO(t)Bu/DMSO promoted α-vinylation of aliphatic, cycloaliphatic, and alkyl aromatic (heteroaromatic) ketones with diverse arylacetylenes.     

Studies on K2CO3-catalyzed 1,4-addition of 1,2-allenic ketones with diethyl malonate: controlled selective synthesis of beta,gamma-unsaturated enones and alpha-pyrones

The K2CO3 (10 mol %)-catalyzed 1,4-addition reaction of diethyl malonate with various substituted 1,2-allenic ketones leading to polyfunctionalized beta,gamma-unsaturated enones 3 or 4 was studied. With 3-unsubstituted 1-substituted-1,2-allenyl ketones, the highly selective formation of beta,gamma-unsaturated enones 4 was observed; with 1,2-allenyl ketones bearing one or two 3-substituents in the allenyl group, only beta,gamma-unsaturated enones 3 with an unmigrated carbon-carbon double bond were produced; with 3-monosubstituted-1,2-allenyl ketones Z-beta,gamma-unsaturated enones 3 were formed with excellent stereoselectivity (E:Z > 96:4); with propadienyl ketones, mixtures of beta,gamma-unsaturated enones 3 and 4 were formed. alpha-Pyrone derivatives were synthesized via the K(2)CO(3)-catalyzed or -promoted reaction of 1,2-allenic ketones with diethyl malonate via a sequential Michael addition-carbon-carbon double bond migration-lactonization process.     

Highly diastereoselective chelation-controlled additions to α-silyloxy ketones

The polar Felkin-Anh, Cornforth-Evans, and Cram-chelation models predict that the addition of organometallic reagents to silyl-protected α-hydroxy ketones proceeds via a nonchelation pathway to give anti-diol addition products. This prediction has held true for the vast majority of additions reported in the literature, and few methods for chelation-controlled additions of organometallic reagents to silyl-protected α-hydroxy ketones have been introduced. Herein, we present a general and highly diastereoselective method for the addition of dialkylzincs and (E)-di-, (E)-tri-, and (Z)-disubstituted vinylzinc reagents to α-silyloxy ketones using alkyl zinc halide Lewis acids, RZnX, to give chelation-controlled products (dr ≥18:1). The compatibility of organozinc reagents with other functional groups makes this method potentially very useful in complex molecule synthesis.     

Chiral Brønsted acid from a cationic gold(I) complex: catalytic enantioselective protonation of silyl enol ethers of ketones

A chiral Br?nsted acid has been developed from a cationic gold(I) disphosphine complex in the presence of alcoholic solvent and applied to the enantioselective protonation reaction of silyl enol ethers of ketones. Various optically active cyclic ketones were obtained in excellent yields and high enantioselectivities, including cyclic ketones bearing aliphatic substrates at the α-position. Furthermore, the application of this Br?nsted acid was extended to the first Br?nsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic substrates, regardless of their E/Z ratio.     

Chemical Tricks To Stabilize Silanones and Their Heavier Homologues with EO Bonds (E=Si–Pb): From Elusive Species to Isolable Building Blocks

In contrast to the well‐established chemistry of ketones (R₂C?O), the reactivity of the elusive heavier congeners R₂E?O (E=Si, Ge, Sn, Pb) is far less explored because of the high polarity of the E?O bonds and hence their tendency to oligomerize with no activation barrier. Very recently, great advances have been achieved in the synthesis of isolable compounds with E?O bonds, including the investigation of donor‐stabilized isolable silanones and the first stable “genuine” germanone. These compounds show drastically different reactivities compared to ketones and represent versatile building blocks in silicon–oxygen and germanium–oxygen chemistry. This and other exciting achievements are described in this Minireview.     

Field dependence of mobilities for gas-phase-protonated monomers and proton-bound dimers of ketones by planar field asymmetric waveform ion mobility spectrometer (PFAIMS)

The dependence of the mobilities of gas-phase ions on electric fields from 0 to 90 Td at ambient pressure was determined for protonated monomers [(MH+(H2O)n] and proton bound dimers [M2H+(H2O)n] for a homologous series of normal ketones, from acetone to decanone (M=C3H6O to C10H20O). This dependence was measured as the normalized function of mobility alpha (E/N) using a planar field asymmetric waveform ion mobility spectrometer (PFAIMS) and the ions were mass-identified using a PFAIMS drift tube coupled to a tandem mass spectrometer. Methods are described to obtain alpha (E/N) from the measurements of compensation voltage versus amplitude of an asymmetric waveform of any shape. Slopes of alpha for MH+ versus E/N were monotonic from 0 to 90 Td for acetone, butanone, and pentanone. Plots for ketones from hexanone to octanone exhibited plateaus at high fields. Nonanone and decanone showed plots with an inversion of slope above 70 Td. Proton bound dimers for ketones with carbon numbers greater than five exhibited slopes for alpha versus E/N, which decreased continuously with increasing E/N. These findings are the first alpha values for ions from a homologous series under atmosphere pressure and are preliminary to explanations of alpha (E/N) with ion structure.     

Interrupted energy transfer: highly selective detection of cyclic ketones in the vapor phase

We detail our efforts toward the selective detection of cyclic ketones, e.g. cyclohexanone, a component of plasticized explosives. Thin films comprised of a conjugated polymer are used to amplify the emission of an emissive receptor via energy transfer. We propose that the energy transfer is dominated by an electron-exchange mechanism to an upper excited state of the fluorophore followed by relaxation and emission to account for the efficient energy transfer in the absence of appreciable spectral overlap. Exposure to cyclic ketones results in a ratiometric fluorescence response. The thin films show orthogonal responses when exposed to cyclic ketones versus acyclic ketones. We demonstrate that the exquisite selectivity is the result of a subtle balance between receptor design and the partition coefficient of molecules into the polymer matrix.     

Synthesis of Novel Pyrimidine Derivatives Containing the Vinylsulfanyl Group by Regio‐ and Stereoselective Addition of Thiouracils to Ethynyl Ketones

A regio‐ and stereoselective method for preparation of novel functionalized pyrimidine derivatives containing the vinylsulfanyl group has been developed based on addition reactions of 2‐thiouracils with phenylethynyl ketones. Reactions with ketones containing the disubstituted triple bond afford adducts of Z‐stereochemistry, whereas addition to ketone with the terminal triple bond gives preferentially products of E‐configuration.     

Sc(OTf)3-catalyzed indolylation of 1,2-allenic ketones: controlled highly selective synthesis of beta-indolyl-alpha,beta-unsaturetated (E)-enones and beta,beta-bisindolyl ketones

[reaction: see text] A novel highly stereoselctive synthesis of beta-indolyl-alpha,beta-unsaturated (E)-enones by the hydroindolylation of the beta,gamma-C=C bond of 1,2-allenic ketones in the presence of 5 mol % Sc(OTf)(3) was developed. beta,beta-Bisindolyl ketones were prepared by using 2.5 equiv of indoles. A stepwise protocol for introducing different indoles was also established.     

Equilibrium acidities and homolytic bond dissociation energies of acidic C-H bonds in alpha-arylacetophenones and related compounds

The equilibrium acidities (pK(AH)s) and the oxidation potentials of the congugate anions [E(ox)(A(-))s] were determined in dimethyl sulfoxide (DMSO) for eight ketones of the structure GCOCH(3) and 20 of the structure RCOCH(2)G, (where R = alkyl, phenyl and G = alkyl, aryl). The homolytic bond dissociation energies (BDEs) for the acidic C-H bonds of the ketones were estimated using the equation BDE(AH) = 1.37pK(AH) + 23.1E(ox)(A(-)) + 73.3. While the equilibrium acidities of GCOCH(3) were found to be dependent on the remote substituent G, the BDE values for the C-H bonds remained essentially invariant (93.5 +/- 0.5 kcal/mol). A linear correlation between pK(AH) values and [E(ox)(A(-))s] was found for the ketones. For RCOCH(2)G ketones, both pK(AH) and BDE values for the adjacent C-H bonds are sensitive to the nature of the substituent G. However, the steric bulk of the aryl group tends to exert a leveling effect on BDEs. The BDE of alpha-9-anthracenylacetophenone is higher than that of alpha-2-anthracenylacetophenone by 3 kcal/mol, reflecting significant steric inhibition of resonance in the 9-substituted system. A range of 80.7-84.4 kcal/mol is observed for RCOCH(2)G ketones. The results are discussed in terms of solvation, steric, and resonance effects. Ab initio density functional theory (DFT) calculations are employed to illustrate the effect of steric interactions on radical and anion geometries. The DFT results parallel the trends in the experimental BDEs of alpha-arylacetophenones.     

Synthesis of β-Fluoroalkyl-β,β-dimethoxy Ketones and β-Fluoroalkyl-β-methoxy-α,β-enones

α-Bromo-β-fluoroalkyl-α,β-enones react with sodium methoxide in methanol to give the corresponding β-fluoroalkyl-β,β-dimethoxy ketones which eliminate methanol molecule to produce a mixture of E/Z-isomeric β-fluoroalkyl-β-methoxyvinyl ketones, the Z isomer prevailing.     

Synthetic organic chemistry with 2-ethoxy-2-(phenylselenenyl)perfluoroalk-2-enenitrile: application to alpha-cyanoperfluoroacylation of aldehydes

(Z)- and (E)-2-Ethoxyperfluoro-2-(phenylselenenyl)alk-2-enenitriles 2-4 prepared by our original method underwent transmetalation on treatment with n-BuLi or EtMgBr, and the successive reaction with aldehyde and ketones afforded the corresponding allylic alcohols 10a-f, 9a, and 11a,b in good to high yields. Hydrolysis of the alcohols gave alpha-cyano-alpha,beta-unsaturated perfluoroalkyl ketones 13a-c, 13e, 12a, and 15a. alpha-Cyanoperfluoroalkyl ketones were easily converted to alpha,beta-unsaturated 3-aryl-2-cyanoallylic alcohols 18-22 having interesting biological activities and chemical reactivities.     

Stereoselective synthesis of ambiphilic alkenes via regioselective methylation of α-trifluoromethanesulfonyl carbonyl compounds with trimethylsilyldiazomethane

α-Trifluoromethanesulfonyl esters, ketones and amides are C-H acids capable of reacting with trimethylsilyldiazomethane to afford the corresponding ambiphilic alkenes. While esters were found to be non-selective, ketones were highly regioselective for O-methylation and displayed variable E/Z stereoselectivity. Amides were observed to be both highly regio- and stereoselective, affording O-methylation with exclusive formation of the Z-alkene.     

Efficient and stereoselective synthesis of beta-trifluoromethyl alpha,beta-unsaturated esters via iron(III) porphyrin-catalyzed olefination of ketones

beta-Trifluoromethyl alpha,beta-unsaturated esters were efficiently prepared by reactions of fluorine-containing ketones with diazo compounds via metalloporphyrin-catalyzed olefination in the presence of triphenylphosphine. The commercially available Fe(III)(TPP)Cl (TPP: tetraphenylporphyrin) is effective for catalyzing the olefination of a variety of trifluoromethyl ketones with different diazoacetate esters under mild conditions. The reactions proceeded with high yields (up to 95% isolated yield) and high stereoselectivity (up to 99% (E)-selectivity).     

A GaCl3-catalyzed [4+1] cycloaddition of alpha,beta-unsaturated carbonyl compounds and isocyanides leading to unsaturated gamma-lactone derivatives

A GaCl3-catalyzed reaction of alpha,beta-unsaturated ketones with isocyanides leading to the formation of unsaturated lactone derivatives is described. This is the first example of the catalytic [4+1] cycloaddition of alpha,beta-unsaturated ketones and isocyanides. GaCl3 is an excellent catalyst due to its lower oxophilicity, which is desirable for all of the key steps, such as E/Z isomerization, cyclization, and deattachment from the products.