A simple synthesis and purification of 1-ferrocenylalkyl alcohols

An alternative method for the preparation of 1-ferrocenylalkyl alcohols has been developed. This involves condensation of ferrocene with carbonyl compounds in concentrated sulfuric acid and addition of the resulting solutions of 1-ferrocenylalkylium ions into aqueous sodium bicarbonate. The mixtures are then treated with thioglycolic acid and the S-(1-ferrocenylalkyl)thioglycolic acids purified via sodium salts and hydrolysed in the presence of copper powder to give 1-ferrocenylalkyl alcohols in good yields.     

Destabilized carbenium ions: α-imidoyl carbenium ions and the electron impact mass spectra of α-haloaldimines and α-haloketimines

A series of α-chloro- and α-bromoketimines compounds (1-9) with different substituents at the α-position and at the imino group has been investigated by electron impact mass spectrometry as possible precursors of the correspondingly substituted α-imidoyl carbenium ion, an important class of destabilized carbenium ions. The main fragmentation of the molecular ions of compounds, 1-9 in the ion source corresponds to an α-cleavage at the imino group; however, fragment ions are also formed by loss of the α-halo substituent. These fragment ions correspond at least formally to α-imidoyl carbenium ions. Their further reactions in dependence on the type of substituents at the imino group and at the α-C atom, were studied by mass-analysed ion kinetic energy and collisional activation mass spectrometry. The results agree with the initial formation of destabilized α-imidoyl carbenium ions but indicate an easy rearrangement of these ions in the presence of suitable alkyl substituents by 1,2- and 1,4-hydrogen shifts to more stable isomers.     

Substitution electrophile du ferrocene et du dimethylferrocene par les derives carbonyles protones : II. Influence des effets stériques et conformationnels lors de la synthèse des α-ferrocénylcarbinols

In strongly acidic media ferrocene and dimethylferrocene react with carbonyl compounds to produce α-ferrocenylcarbinols. ¹H NMR studies show that the alcohols are quickly transformed into α-ferrocenylcarbenium ions which after hydrolysis afford the alcohols in high yields. In all cases mono-substitution products are only obtained. With dimethyl ferrocene the ratio of 2-isomer versus 3-isomer indicate a higher reactivity of the α position when small electrophiles are used ; on the contrary condensation of ketones occur preferentially at the β position.     

The nef reaction on trialkylsilyl nitronates promoted by m-chloroper-benzoic acid. An efficient route to α-alkoxyketones from nitroalkanes.

Treatment of a nitroalkene with nucleophiles, followed by silylation of the resulting nitroalkane and subsequent treatment with m-chloroperbenzoic acid, provides α-functionalized carbonyl compounds in good yields.     

Basicity and structure of α,Β-unsaturated heterocyclic ketones

The constants of the protolytic equilibrium and the displacement of the frequency of the stretching vibrations of the hydroxy group of phenol taking place under the influence of the formation of a hydrogen bond with the compounds studied have been measured for dibenzylideneacetone and dibenzylidenecycloalkanones (with five-, six-, and seven-membered rings) and their furan and selenophene analogs. It has been shown that the screening of the carbonyl group of the aliphatic ring creates considerable steric hindrance for the solvation of the carbenium ions formed in an acid medium, as the result of which the constants of the protolytic equilibrium fall on passing from compounds with an open chain to the cycloalkanone derivatives. The inclusion of a carbonyl group in a five-membered aliphatic ring creates more favorable conditions for conjugation than exist in analogous compounds with an open chain and in those with six- and seven-membered rings, in consequence of which the capacity for forming a hydrogen bond changes in the corresponding sequence.For preceding communication, see [1].     

Memory of Chirality in Flow Electrochemistry: Fast Optimisation with DoE and Online 2D-HPLC

Amino acid derivatives undergo non-Kolbe electrolysis to afford enantiomerically enriched α-alkoxyamino derivatives through intermediate chiral carbenium ions. The products contain N,O-acetals which are important structural motifs found in bioactive natural products. The reaction is performed in a continuous flow electrochemical reactor coupled to a 2D-HPLC for immediate online analysis. This allowed a fast screening of temperature, electrode material, current, flow-rate and concentration in a DoE approach. The combination with online HPLC demonstrates that also stereoselective reactions can benefit from a hugely accelerated optimisation by combining flow electrochemistry with multidimensional analysis.     

Destabilized carbenium ions. Secondary and tertiary α-acetylbenzyl cations and α-benzoylbenzyl cations

The secondary α-acetylbenzyl and α-benzoylbenzyl cations, as well as their tertiary analogues, have been generated in a mass spectrometer by electron impact induced fragmentation of the corresponding α-bromoketones. These ions belong to the interesting family of destabilized α-acylcarbenium ions. While primary α-acylcarbenium ions appear to be unstable, the secondary and tertiaiy ions exhibit the usual behaviour of stable entities in a potential energy well. This can be attributed to a ‘push-pull’ substitution at the carbenium ion centre by an electron-releasing phenyl group and an electron-withdrawing acyl substituent. The characteristic unimolecular reaction of the metastaible secondary and tertiary α-acylbenzyl cations is the elimination of CO by a rearrangement reaction involving a 1,2-shift of a methyl group and a phenyl group, respectively. The loss of CO is accompanied by a very large kinetic energy release, which gives rise to broad and dish-topped peaks for this process in the mass-analysed ion kinetic energy spectra of the corresponding ions. This behaviour is attributed to the rigid critical configuration of a corner-protonatei cyclopropanone derivative and a bridged phenonium ion derivative, respectively, for this reaction. For the tertiary α-acetyl-α-methylbenzyl cations, it has been shown by deuterium labelling and by comparison of collisional activation spectra that these ions equilibrate prior to decomposition with their ‘protomer’ derivatives formed by proton migration from the α-methyl substituent to the carbonyl group and to the benzene ring.     

A unique transition metal-stabilized silicon cation

Trivalent silicon cations are exceptionally strong electron pair acceptors that react, either desired or undesired, with almost any σ and π basic molecule. One way of intramolecular attenuation of the Lewis acidity of these superelectrophiles is by installation of a ferrocene unit at the electron-deficient silicon atom. While well-understood for isoelectronic α-ferrocenyl-substituted carbenium ions and also boranes, the stabilizing interactions between the ferrocene backbone and a positively charged silicon atom are not clear due to the challenge of crystallizing such cations. The structural characterization of our ferrocene-stabilized silicon cation now reveals an unprecedented bonding motif different from its analogues. An extreme dip angle of the silicon atom toward the iron atom is explained by two three-center-two-electron (3c2e) bonds through participation of both the upper and the lower aromatic rings of the ferrocene sandwich structure. The positive charge is still localized at the silicon atom that also retains a quasi-planar configuration.     

α-imino carbenium ions: Is the α-imino group really destabilizing?

According to ab initio calculations, there is good evidence that α-imino carbenium ions exist as bridged carbocations. Furthermore, the energy differences between planar and bridged structures are much larger than for the corresponding α-acyl carbenium ions. Compared to the other α-electron withdrawing groups studied, the α-imino group does not lead to a destabilized carbenium ion; α-imino carbenium ions would therefore seem to be possibly useful synthetic intermediates.     

Enantioselective Synthesis of β-Amino Acid Derivatives Enabled by Ligand-Controlled Reversal of Hydrocupration Regiochemistry

A Cu-catalyzed enantioselective hydroamination of α,β-unsaturated carbonyl compounds for the synthesis of β-amino acid derivatives was achieved through ligand-controlled reversal of the hydrocupration regioselectivity. While the hydrocupration of α,β-unsaturated carbonyl compounds to form α-cuprated species has been extensively investigated, we report herein that, in the presence of an appropriate ancillary chiral ligand, the opposite regiochemistry can be observed for cinnamic acid derivatives, leading to the delivery of the copper to the β-position. This copper can react with an electrophilic aminating reagent, 1,2-benzisoxazole, to provide enantioenriched β-amino acid derivatives, which are important building blocks for the synthesis of natural products and bioactive small molecules.     

Effect of the Electronic Structure of Carbenium and Silylium Ions on Their Chemical Behavior

Being isoelectronic analogs, silylium and carbenium ions exhibit quite a different reactivity toward nucleophiles. This is explained by their different electronic structures and charge distributions: In silylium ions the positive charge is almost completely concentrated on the silicon atom, and hydrogen atoms on the cationic center are hydride in nature, wheteas in carbenium ions, the positive charge is uniformly distributed between the carbenoid center and hydrogen atoms.     

Synthesis of 2-Ferrocenyl-2-(Dialkyl Hydroxymethyl)D-1,3-Dithianes

The reactions of lithiated 2-ferrocenyl-1,3-dithiane with alkyl carbonyl compounds are studied. Fifteen of title compounds which are new ferrocene derivatives were synthesized and structurally characterized by elemental analysis, IR and 1H NMR spectra. The 1H NMR spectra of the dithiane compounds are briefly discussed.     

Diastereo- and enantioselective preparation of β-alkylhomoallylic alcohols : Synthesis of serricornin and corynomycolic acid

A new and efficient method for the preparation of four possible stereoisomers of β-alkylhomoallylic alcohols 1 has been developed which is based on the diastereoselective addition of nucleophiles to optically active α-alkyl-β-trimethylsilyl-β,γ-unsaturated carbonyl compounds. The utility of this reaction is demonstrated by the synthesis of naturally occurring serricornin and corynomycolic acid.     

Metallocenyl cations : III. Cymantrenyl carbenium ions containing one phosphine ligand

A number of carbinols, cyclopentadienylmanganese tricarbonyl derivatives of general formula (CO)₂LMnC₅H₄C(OH)RR′ (I) (L = PPh₃ or P(isoC₃H₇)₃, R and R′ = H, Me, Et, Ph) have been synthesised. In solution, in the presence of CF₃COOH they form stable secondary and tertiary carbenium ions, stabilised by the (CO)₂LMnC₅H₄ group. IR spectra and ¹H and ¹³C NMR spectra of the carbenium ions were recorded. Substitution of a tertiary phosphine for a carbonyl group sharply increased the stability of the α-cymantrenylcarbenium ions.     

Direct Synthesis of α-Amino Acid Derivatives by Hydrative Amination of Alkynes

α-Amino acid derivatives are key components of the molecules of life. The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we report a practical method for the preparation of α-amino acid derivatives via direct hydrative amination of activated alkynes under mild conditions, relying on sulfinamides as the nitrogen source. Computational studies suggest that the reaction is enabled by a new type of sulfonium [2,3]-sigmatropic rearrangement.     

Strain-Induced Nucleophilic Ring Opening of Donor–Acceptor Cyclopropenes for Synthesis of Monosubstituted Succinic Acid Derivatives

1,2,3-Trisubstituted donor–acceptor cyclopropenes (DACPs) generated in situ from enoldiazo compounds react with nucleophiles to form α-substituted succinic acid derivatives in high yields. Initial dirhodium(II) carboxylate catalysis rapidly converts enoldiazo-acetates or -acetamides to DACPs that undergo catalyst-free Favorskii ring opening with amines, and also with anilines, alcohols, and thiols, when facilitated by catalytic amounts of 4-dimethylaminopyridine (DMAP). This methodology provides easy access to mixed esters and amides of monosubstituted succinic acids, including derivatives of naturally occurring compounds. It also affords dihydrazide, dihydroxamic acid, and diamide derivatives, as well as α-substituted tetrahydropyridazine-3,6-diones in high yields. Attempts to generate optically enriched DACPs were not successful because their populations having the R and S configurations formed with a chiral dirhodium catalyst are quite similar, and the loss of enantiocontrol likely originates from the DACP ring forming step which is reversible with its intermediate metal carbene.     

Reduction and Reductive Alkylation of α-tert-Butylthio Carbonyl Compounds. An Efficient Method for Stepwise α-Alkylation of Esters,Nitriles and Ketones Via the α-Tert-Butylthio Derivatives

An efficient and generally applicable method for stepwise α-alkylatton of esters, nitriles, and ketones via the α-tert-butylthio derivatives is described. The method involves reductive-protonation and reductive-alkylation of α-alkylthio α,α-bis-alkylated carbonyl compounds which are prepared by stepwise alkylation of the corresponding simple α-alkylthio carbonyl precursors. The reduction is conveniently performed by use of stoichiometric amounts of a dissolving metal, particularly lithium, affording correspondingly the α-mono-and the α,α-bis-alkylated carbonyl compounds in good yields.     

Enantioselective α-heterofunctionalisation of carbonyl compounds: organocatalysis is the simplest approach

Enantioselective organocatalytic processes have reached maturity in recent years with an impressive number of applications now available. The application of these advantageous methodologies to the construction of chiral α-hetereofunctionalised carbonyl compounds allows us to obtain important chiral building blocks, such as α-amino acids, α-amino alcohols, aziridines, epoxides, 1,2-diols and α-sulfenylated, selenenylated and halogenated carbonyl derivatives. Proline, imidazolidinone derivatives, cinchona alkaloids and their ammonium salts, as well as Brønsted acid derivatives, have been used as chiral catalysts for these purposes. A survey of contributions in this field will be discussed throughout this review.     

27 Years of Catalytic Carbonylative Coupling Reactions in Hungary (1994–2021)

Palladium-catalyzed carbonylation reactions, in the presence of nucleophiles, serve as very potent tools for the conversion of aryl and alkenyl halides or halide equivalents to carboxylic acid derivatives or to other carbonyl compounds. There are a vast number of applications for the synthesis of simple building blocks as well as for the functionalization of biologically important skeletons. This review covers the history of carbonylative coupling reactions in Hungary between the years 1994 and 2021.     

Palladium(II)-catalyzed tandem intramolecular aminopalladation of alkynylanilines and conjugate addition for synthesis of 2,3-disubstituted indole derivatives

An efficient method for the synthesis of 2,3-disubstituted indoles with high selectivity from 2-ethynylaniline derivatives and α,β-unsaturated carbonyl compounds was developed. This Pd(II)-catalyzed reaction involves tandem intramolecular aminopalladation, olefin insertion and protonolysis of the carbon-palladium bond with the regeneration of Pd(II) species in the presence of halide ions.