Tamas Holczbauer

Hungarian Academy of Sciences | HAS · Institute of Organic Chemistry

Iron(II) complexes containing ligands with a R2P–P–PR2 unit were synthesized by metathesis reactions. With R = tBu, a mixture of two isomers is formed; in one of them, the terminal phosphorus binds to the Fe center (ylidic structure), while in the other one, the central P atom is linked to Fe. Starting from differently functionalized parent triphos...

Carbohydrate-based macrocycles can be enantioselective catalysts in certain reactions. Previously, it was proven that the carbohydrate moiety could affect the catalytic activity of the monoaza-15-crown-5 type macrocycles derived from sugars. According to our experiments so far, the most effective enantioselective catalysts were the d-glucose- and t...

The reduction of 1,1‐dichloro‐2,5‐bistrimethylsilyl‐3,4‐diphenylsilole to silolide dianion by alkali metals was investigated. As previously demonstrated, the outcome of the reaction depends strongly on the applied alkali metal, solvent, reaction conditions, and substituent pattern. We showed that lithium is a powerful reducing agent in THF or DME s...

A focused library of 1-adamantyl arylthiophosphonates was prepared in racemic form. An enantioseparation method was developed for P-stereogenic thiophosphonates using (S)-1-phenylethylamine as the resolving agent. Under optimized conditions, three out of the five arylthiophosphonates were prepared in enantiopure form (ee > 99%). The subsequent desu...

A novel metal-free synthesis of indenone derivatives mediated by CBr4 and diethyl phosphonate is reported. The methodology has a relatively wide substrate scope and is suitable to access a π-extended indenone and an s-indacene-1,5-dione derivative as well.

A library of racemic H-phosphinates incorporating a variety of alkoxy groups or substituted aryl groups was prepared. Starting with resolving agent screening, an efficient enantioseparation method was developed and optimized using (R,R)-(1-naphthyl)-spiro-TADDOL as the resolving agent. This method gave 12 out of 16 H-phosphinates with an ee of abov...

The synthesis and properties of a series of unsymmetrical thienopentalenes are explored, including both monoareno and diareno derivatives. For the synthesis of monoareno pentalenes, a carbopalladation cascade reaction between alkynes and gem-dibromoolefins was applied. Diareno pentalene derivatives were accessed via gold-catalyzed cyclization of di...

Enantioenriched, highly functionalized cyclopropane derivatives were prepared by a simple and green approach using monosaccharide‐based chiral crown ethers as phase transfer catalysts. The Michael‐initiated ring closure (MIRC) reactions of diethyl bromomalonate with 2‐cyano‐3‐phenylacrylate took place with complete diastereoselectivity in the prese...

Secondary phosphine oxides incorporating various aryl and alkyl groups were synthesized in racemic form, and these products formed the library reported in this study. TADDOL derivatives were used to obtain the optical resolution of these P-stereogenic secondary phosphine oxides. The developed resolution method showed a good scope under the optimize...

Crystal structures of diastereomeric salt pairs, as well as double salts are rare to find in the literature [1, 2]. Present work involves the crystallization and structural elucidation of two constitutional isomer double salts along with their related diastereomeric salt pairs. The investigated systems are 1-cyclohexylethylammonium 2-chloromandelat...

Herein, the design and synthesis of a click-derived Pd-complex merged with a photoswitchable azobenzene unit is presented. While in thetrans-form of the switch the complex showed limited solubility, the photogeneratedcis-form rendered the molecule soluble in polar solvents. This light-controllable solubility was exploited to affect the catalytic ac...

The number of crystal structures of diastereomeric salt pairs and especially of double salts is limited in the literature. This work exceptionally presents the structures of two constitutional isomer double salts along with their related diastereomeric salt pairs, which were successfully crystallized and their structures elucidated presenting two c...

A series of half-sandwich polypyridyl complexes was synthesized and compared focusing on structural, cytotoxic and aqueous solution behaviour. The formula of the synthesized complexes is [M(arene)(N,N)Cl]Cl, where M: Ru or...

The coordination properties of four hydroxypyridinecarboxylates, designed for the treatment of iron-overloading conditions as bidentate O,O'-donor ligands, have been studied with ZnII in the solid state. The coordination compounds [Zn(A1)2(H2O)2] (1), [Zn(A2)2(H2O)] (2), [Zn(A3)2(H2O)]·2H2O (3) and [Zn2(B1)4(H2O)2]·4H2O (4), where the ligands are 1...

Solution speciation of Rh(η5‐C5Me5), Ru(η6‐p‐cymene) and Ru(η6‐toluene) complexes of 2,4‐pyridinedicarboxylic acid (2,4‐dipicH2) was studied and compared to that of 2‐picolinic acid (picH) in addition to their reactivity towards chloride and bromide ions, 1‐methylimidazole and guanosine. Structures of [Rh(η5‐C5Me5)(2,4‐dipicH)Cl]∙3H2O (1), 2[Ru(η6‐...

An estrone-salicylaldehyde thiosemicarbazone hybrid (estrone-TSC) containing integrated domains was designed and synthesized with excellent yield via the condensation reaction of thiosemicarbazide and 2-formyl-estrone under optimized microwave reaction conditions. A structurally...

Concise syntheses of (−)‐minovincine and (−)‐aspidofractinine were achieved using easily available and inexpensive reagents and catalyst. A key element of the strategy was the use of a sequence of cascade reactions to rapidly construct the penta‐ and hexacyclic frameworks. To streamline the synthetic routes, the steric effect was used to secure var...

We report eight‐step syntheses of (–)‐ minovincine and (–)‐aspidofractinine using easily available and inexpensive reagents and catalyst. A key element of the strategy was the utilization of the chain of cascade reactions to rapidly construct the penta‐ and hexacyclic frameworks. These cascade transformations included organocatalytic Michael‐aldol...

In this paper, we report the synthesis and characterization of a series of phosphanyl‐substituted siloles. The chemical modification (oxidation, sulfurization, alkylation and complexation) results in a change in the energy level of frontier orbitals, which has further been studied by UV‐Vis absorption spectroscopy and electrochemistry. Significantl...

According to the currently accepted structure-property relationships, aceno-pentalenes with angular shape (fused to the 1,2-bond of the acene) exhibit higher antiaromaticity than those with linear shape (fused to the 2,3-bond of the acene). To explore and expand the current view, we designed and synthesized molecules where two isomeric, yet, differ...

Several dialkyl‐arylphosphine oxides were prepared, and the enantioseparation of the corresponding racemates was elaborated with host‐guest complexation using TADDOL‐derivatives. The crystallization conditions were optimized and two separate crystallization methods, one in organic solvent, and the other in water, were found to yield five examples o...

According to the currently accepted structure-property relationships, aceno-pentalenes with angular shape (fused to the 1,2-bond of the acene) exhibit higher antiaromaticity than those with linear shape (fused to the 2,3-bond of the acene). To explore and expand the current view, we designed and synthesized molecules where two isomeric, yet, differ...

Invited for the cover of this issue is the group of Tibor Soós at the Hungarian Academy of Sciences. The image depicts a metaphorical representation of the catalytic cycles and the size‐exclusion concept of the reported metal‐free, one‐pot reductive Ireland–Claisen rearrangement. Read the full text of the article at 10.1002/chem.201805208. “A metal...

A reductive Ireland–Claisen reaction was developed utilizing a boron‐based Lewis acid catalyst with size‐exclusion design. In the graphical art, the juggler throws balls up into the air to create the pattern of a catalytic cycle. In addition, the juggler has to wear special gloves with small holes (size‐exclusion) to catch and carry the balls. Larg...

The reductive Ireland‐Claisen rearrangement via borane mediated hydrosilylation is reported. The method employs borane catalyst with a special structural design and affords access to synthetically relevant product with high diastereoselectivity. Depending on electronic and structural parameter, the reaction can be coupled with a 1,3‐allylic shift,...

Polymorphism of porous, non-covalently bonded ionic organic frameworks is reported. They are constructed by hydrogen bonds and anion…π interactions. In a solvatomorphic lattice pyridine takes part in the framework formation....

The first planar lithium silolide characterized by X-ray crystallographically is reported. The structural data, NMR and DFT results reveal high aromatic character, with the unusual dominance of non-classical resonance structures.

Phosphine–phosphoramidites (PPAs) are heterobidentate ligands that have been developed in the last two decades and have been used successfully in asymmetric catalytic reactions. A single crystal of the PPA (11b S )- N -[(2 S ,4 S )-4-(diphenylphosphanyl)pentan-2-yl]- N -methyldinaphtho[2,1- d :1′,2′- f ][1,3,2]dioxaphosphepin-4-amine, C 38 H 35 NO...

The cover picture shows a lightning strike, a sudden release of energy, which is used to symbolize the enhanced and unusual reactivity of strained molecules. As an example, strained captodative benzylideneazetidinones function as potent reaction partners in thermal [2+2] cycloadditions with nitro alkenes. The relief of strain during the cycloadditi...

A detailed thermochemical and structural study of the phenylpiracetam enantiomer system was performed by characterizing the solid solutions, rationalizing the structural driving force for their formation as well as identifying a common structural origin responsible for the formation of solid solutions of enantiomers. Enantiomerically pure phenylpir...

Strained, captodative benzylidene-azetidinones are demonstrated to function as potent reaction partners in thermal [2+2] cycloaddition with nitro alkenes. The relief of strain during the cycloaddition could be leveraged to secure the kinetic and thermodynamic stability for the amino-nitro-cyclobutane ring. Accordingly, this mild and robust procedur...

We report an expedient approach to highly functionalized cis- and trans-decalines that could function as key structural subunits toward the synthesis of various classes of terpenoids. Key to the strategy is an organocatalyzed Robinson annulation reaction of the Nazarov reagent that affords chiral enone building blocks with high enantioselectivities...

The first homoleptic trinuclear arylgold(i) complex, [Au3(L')2](NO3) (3), based on an ortho-phenyl metallated aryl-diphosphine ligand (L' = o-C6H4PPh(C15H10O)PPh2), has been obtained through a new thermolytic reaction of the corresponding diauracycle, [Au2(L)2](NO3)2 (L = xantphos). The formation of 3 involves activation of the ortho-phenyl C-H bon...

An efficient, regioselective synthesis has been developed for the preparation of 5-(diphenylmethylene)-1H-pyrrol-2(5H)-ones from readily available 1H-pyrroles by sequential dibromination and selective organometallic bromine/lithium exchange followed by reaction with benzophenone. Comparison of various N-substituents was shown to demonstrate the hig...

In the title complex, [Ni(SO4)(C5H8N2)3(H2O)2], the Ni^II ion is coordinated by three facial 1-ethyl-1H-imidazole ligands, one monodentate sulfate ligand and two water molecules in a slightly distorted octahedral coordination environment. In the crystal, two pairs of O—H...O hydrogen bonds link complex molecules, forming inversion dimers incorporat...

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and...

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and...

The first synthesis of new organocatalysts with 1-phenylpyrrole atropisomeric skeleton containing a thiourea group is reported. A possible structural reason for the stereochemical lability of an atropisomeric intermediate is described together with a way to preserve the isomeric purity during the synthesis. The catalytic activities of the new atrop...

Efficient synthesis of several new atropisomeric amino alcohols having 1-phenyl-1H-pyrrole skeleton are reported. Steric arrangements of the products were confirmed by a single-crystal X-ray measurement. The consequences of the size of the N-substituents on enantioinduction were examined by employing the enantioselective catalytic addition of dieth...

The mechanism of the addition of acetylacetone to β-nitrostyrene catalyzed by a cinchona based squaramide catalyst was studied in detail under synthetically relevant conditions. The reaction was monitored by in situ IR and 1H-NMR spectroscopy and a reaction mechanism was proposed based on these kinetics experiments. It was found that the reaction s...

Bannucine is an Aspidosperma alkaloid isolated from the dried leaves of Catharanthus roseus. The molecule is a derivative of vindoline bearing a C10 substituent, a pattern common to the antineoplastic dimeric indole alkaloids of C. roseus. In bannucine, a 2-pyrrolidone moiety is attached at C5′ to the aromatic ring of the vindoline core at C10. In...

Owing to the ring strain and α-heteroatom effect, the four-membered heterocyclic ketones can undergo direct cross-aldol and -ketol reactions without the need for preformed enol or "enolate-like" intermediates. Besides the organocatalyzed cross-ketol addition onto their highly active carbonyl group, their ability to act as a nucleophilic donor has a...

An unprecedentedly thermo- and air-stable Pd0 complex from readily available electron-poor trifluoromethylated phosphine was serendipitously discovered. As detailed and comparative DFT calculations indicate, the stability of the complex is associated with unusually strong ligand–ligand noncovalent interactions. The unique stability and the presence...

The resolution of 1-i-butyl-3-methyl-3-phospholene 1-oxide was studied applying TADDOL [(−)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane], spiro-TADDOL [(−)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol], or the acidic and neutral Ca2+ salts of (−)-O,O′-dibenzoyl- and (−)-O,O′-di-p-toluoyl-(2R,3R)-tartaric ac...

A series of methylene-linked boron/nitrogen geminal Lewis pairs were synthesized and the impacts of sterical effect on their chemical behavior were systematically investigated. Increasing the steric demand around the boron atom is manifested first by an incremental change in the structure of the resulting dative adducts. Accordingly, in the case of...

1-n-Propoxy-3-methyl-3-phospholene 1-oxide was prepared in optically active form by extending resolution methods applying (-)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane ('TADDOL') and (-)-(2R,3R)-alpha,alpha,alpha,alpha'-tetraphenyl-1,4-dioxaspiro[4.5]clecan-2,3-dimethanol ('spiro-TADDOL'), as well as the acidic and neutral Ca2+ s...

The resolution methods applying (-)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane ("TADDOL"), (-)-(2R,3R)-α,α,α',α'-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol ("spiro-TADDOL"), as well as the acidic and neutral Ca(2+) salts of (-)-O,O'-dibenzoyl- and (-)-O,O'-di-p-toluoyl-(2R,3R)-tartaric acid were extended for the preparati...

The first enzyme-catalyzed kinetic resolution of tert-butyl-3-hydroxy-4-phenylpyrrolidine-1-carboxylate is presented. Enzyme, solvent and temperature optimization resulted in a new resolution method with E = 40 enantioselectivity. The acetate derivative of the (+)-(3S,4R) enantiomer formed while the (−)-(3R,4S) isomer remained intact. Very good ena...

Synthesis, structure determination and in vitro antiproliferative assay of a series of novel ferrocenenyl hydrazones containing 4-halopyridazin-3(2H)-one fragment(s) and three representative N-aryl-substituted (Sp)-ferroceno[d]pyridazinones are presented. The model compounds can be considered as different assemblies of the potential binding sites c...

The anion recognition properties of the newly synthesized 5,5-dioxophenothiazine bis(phenylurea) and bis(phenylthiourea) were investigated in acetonitrile using UV-vis spectroscopy. While most of the studied anions were bound only by the neutral receptors, fluoride and acetate were complexed even by the deprotonated ones.

A seri es of 2- arylmethylideneferroceno[ e ]cyclohexanon e was prepared by base-c atalysed conde nsation of ferroceno[ b ]cyclohexa none with a variety of aryl aldehyde s including for mylferrocen e. The decreased reactivity of these novel chal cones towards nucleop hic reagents was in terpreted by the compa rison of DFT reactivity in dices calcul...

A novel, superbase induced diastereoselective transformation of benzylamino groups containing oxiranes has provided a series of trans-1,2,3-trisubstituted azetidines in good yields. The reaction of the corresponding optically active cis-2,3-disubstituted oxirane yielded the azetidine derivative as a single enantiomer. The structures of the new azet...

A novel, superbase induced diastereoselective transformation of benzylamino groups containing oxiranes has provided a series of trans-1,2,3-trisubstituted azetidines in good yields. The reaction of the corresponding optically active cis-2,3-disubstituted oxirane yielded the azetidine derivative as a single enantiomer. The structures of the new azet...

The microwave-assisted double Kabachnik–Fields (phospha-Mannich) reaction of benzylamine and arylamines, two equivalents of paraformaldehyde and the P(O)H reagent, such as dialkyl phosphites, ethyl phenyl-H-phosphinate and diphenylphosphine oxide gave the bis(P(O)CH2)amine derivatives in good yields. The bis(diphenylphosphinoxido) derivatives were...

Highly regioselective mono-, di- and tribrominations of 1-[2-(trifluoromethyl)phenyl]-1H-pyrrole and several derivatives were accomplished with N-bromosuccinimide under mild conditions. Combined applications of these brominations with organometallic (e.g., bromine/lithium exchange or metalation) reactions provided a novel regioflexible route to new...

Chiral salen complexes with C2-symmetry were prepared by the complexation of a selection of transition metal salts with a novel ligand obtained via controlled diastereoselective diaza-Cope rearrangement of a diimine which was resulted from the condensation 2,2′-[(1R,2R)-1,2-diaminoethane-1,2-diyl]diphenol with formylferrocene. On the effect of air...

Liquid–liquid phase asymmetric Darzens condensations were carried out in the presence of d-glucose- and d-mannose-based crown ethers 1 and 2 as the catalyst. The use of d-glucose-based lariat ether 1 as the catalyst gave the best results. The reaction of 4-phenyl-α-chloroacetophenone, 2-chloro-1-tetralone, and 2-chloro-1-indanone with various aroma...

The microwave-assisted double Kabachnik–Fields (phospha-Mannich) reaction of cyclohexylamine, two equivalents of paraformaldehyde and > P(O)H species, such as dialkyl phosphites, ethyl phenyl-H-phosphinate and diphenylphosphine oxide affords the title compounds in good yields. The bis(diphenylphosphinoxido) derivative was converted to the correspon...

A novel, highly efficient method has been developed for the separation of the optical isomers of 1-[2-carboxy-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acid with methyl (R)-2-phenylglycinate. The structural aspects of chiral discrimination have been discussed via comparison of the molecular structures and the packing energies of the diaste...

The importance and reactivity consequences of the double diastereocontrol in noncovalent bifunctional organocatalysis were studied. The results suggest that the bifunctional thioureas can have synthetic limitations in multicomponent domino or autotandem catalysis. Nevertheless, we provided a means to exploit this behavior and used the configuration...

Liquid–liquid phase asymmetric Darzens condensations were promoted by d-glucose- and d-mannose-based crown ethers. The corresponding aromatic and heteroaromatic α,β-epoxyketones were obtained with moderate to high enantioselectivities (up to 96%) as well as diastereoselectivities (up to 98:2) under mild reaction conditions. The absolute configurati...

A method for the synthesis of medium-sized 1,5-benzothiazocines by ring enlargement of 1,3-benzothiazines has been developed. When N-alkyl-1,3-benzothiazines were reacted with dimethyl acetylenedicarboxylate in acetonitrile at room temperature, regioisomeric 5,6-dihydro-2H-1,5-benzothiazocines and 5,6-dihydro-4H-1,5-benzothiazocines were obtained a...

The ring-enlargement reactions of monochloro-β-lactam-fused 2-aryl-1,3-benzothiazines revealed that the reactions of ortho-nitro aryl-substituted derivatives with sodium methoxide in methanol provided two products, depending on the amount of the base. With 2equiv of reagent, the expected 1,4-benzothiazepines were obtained. Somewhat surprisingly, tr...

By means of a base-catalysed ring enlargement of triazapentalenoindenes resulting from diasteroselective anhydride-induced ring transformation of chiral aminoalcohol-derived zwitterionic 2,3-dihydroimidazo[2,1-a]phthalazinium-olates, a series of pyrazolo[1,5-d][1,4]diazocin-7(6H)-ones with central and conformational chirality were obtained in enant...

Thermal ring transformation ability of unsaturated N-bridgehead fused pyrimidin-4(3H)-ones A is governed by both the steric and the electrostatic interactions between the oxygen of the carbonyl group and the substituent in the peri position.

AbstractSubstituted 2H-1,3-benzothiazines and 2,3-dihydro-1,4-benzothiazepines react with dimethyl acetylenedicarboxylate in aqueous methanol to give new, unexpected condensed-skeleton heterocycles. The structures of the new compounds were determined by 1H and 13C nuclear magnetic resonance (NMR), two-dimensional (2D) heteronuclear multiple-bond co...

The tautomers of 3-ethoxycarbonyl-2-phenyl-4,1-benzothiazepine and its 2-(4-methylphenyl) and 2-(4-chlorophenyl) derivatives, identified in solution by spectroscopic means, could be separated in the form of single-crystals suitable for X-ray diffraction. This is at present a unique situation in the literature on desmotropy. For the three desmotropi...

The title compound, [PtCl(2)(C(13)H(11)O(2)P)(2)]·CHCl(3), has a rare PtCl(2) bridging of two dibenzooxaphospho-rine ligands through the metal atom. The Pt(II) ion is in a slightly distorted square-planar environment. The trichloro-methane solvent mol-ecule shows rotational disorder (major occupancy is 0.75) and is placed near to the inversion cent...