Palladium-Catalyzed Monoarylation of Arylhydrazines with Aryl Tosylates.

A palladium-catalyzed C-N bond coupling reaction between arylhydrazines and aryl tosylates for facile synthesis of unsymmetrical N,N-diarylhydrazines has been developed. Employing the catalyst system of Pd(TFA)2 associated with newly developed phosphine ligand L1, the monoarylation of arylhydrazine proceeds smoothly to afford desired products in good-to-excellent yields (up to 95%) with good functional group compatibility. This method provides an alternative synthetic pathway for accessing structurally diversified N,N-diarylhydrazines from simple and easily accessible coupling components.

Getting the sterics just right: a five-coordinate iridium trisboryl complex that reacts with C-H bonds at room temperature.

Five-coordinate boryl complexes relevant to Ir mediated C-H borylations have been synthesized, providing a glimpse of the most fundamental step in the catalytic cycle for the first time.

Design of and mechanistic studies on a biomimetic iron-imidazole catalyst system for epoxidation of olefins with hydrogen peroxide.

Novel iron catalysts, both defined and in situ generated, for the epoxidation of aromatic and aliphatic olefins with hydrogen peroxide as terminal oxidant are described. Our catalyst approach is based on bio-inspired 1-aryl-substituted imidazoles in combination with cheap and abundant iron trichloride hexahydrate. We show that the free 2-position of the imidazole ligand motif plays a key role for catalytic activity, as substitution leads to a dramatic depletion of yield and conversion. X-ray studies, UV/Vis titrations, and NMR studies were carried out to clarify the mechanism.

Green and efficient synthesis of sulfonamides catalyzed by nano-Ru/Fe(3)O(4).

The environmentally benign synthesis of carbon-nitrogen bonds continues to be an active and challenging field of chemical research. Here, a novel, environmentally benign method for the direct coupling of sulfonamides and alcohols is described. Despite the importance of sulfonamide derivatives as intermediates in drug synthesis, till now such transformations are rarely known. For the first time a domino dehydrogenation-condensation-hydrogenation sequence of alcohols and sulfonamides has been realized in the presence of a nanostructured catalyst. The magnetic property of the catalyst system allows for convenient isolation of the product and efficient recycling of the catalyst. A variety of coupling reactions of benzylic alcohols and sulfonamides including various heterocycles were successfully realized, often with >80% isolated yield. Advantageously, only one equivalent of the primary alcohol is consumed in the process. Mechanistic investigations of the competitive reactions of benzyl alcohol and d(7)-benzyl alcohol with p-toluenesulfonamide revealed a kinetic isotope effect (k(H)/k(D)) of 2.86 (+/-0.109) for the dehydrogenation of benzyl alcohol and 0.74 (+/-0.021) for the hydrogenation of N-benzylidene-p-toluenesulfonamide intermediate, which suggests dehydrogenation of the alcohol to be the rate determining step.

Biomimetic iron-catalyzed asymmetric epoxidation of aromatic alkenes by using hydrogen peroxide.

A novel and general biomimetic non-heme Fe-catalyzed asymmetric epoxidation of aromatic alkenes by using hydrogen peroxide is reported herein. The catalyst consists of ferric chloride hexahydrate (FeCl(3)6 H(2)O), pyridine-2,6-dicarboxylic acid (H(2)(pydic)), and readily accessible chiral N-arenesulfonyl-N'-benzyl-substituted ethylenediamine ligands. The asymmetric epoxidation of styrenes with this system gave high conversions but poor enantiomeric excesses (ee), whereas larger alkenes gave high conversions and ee values. For the epoxidation of trans-stilbene (1 a), the ligands (S,S)-N-(4-toluenesulfonyl)-1,2-diphenylethylenediamine ((S,S)-4 a) and its N'-benzylated derivative ((S,S)-5 a) gave opposite enantiomers of trans-stilbene oxide, that is, (S,S)-2 a and (R,R)-2 a, respectively. The enantioselectivity of alkene epoxidation is controlled by steric and electronic factors, although steric effects are more dominant. Preliminary mechanistic studies suggest the in situ formation of several chiral Fe-complexes, such as [FeCl(L*)(2)(pydic)]HCl (L*=(S,S)-4 a or (S,S)-5 a in the catalyst mixture), which were identified by ESIMS. A UV/Vis study of the catalyst mixture, which consisted of FeCl(3)6 H(2)O, H(2)(pydic), and (S,S)-4 a, suggested the formation of a new species with an absorbance peak at lambda=465 nm upon treatment with hydrogen peroxide. With the aid of two independent spin traps, we could confirm by EPR spectroscopy that the reaction proceeds via radical intermediates. Kinetic studies with deuterated styrenes showed inverse secondary kinetic isotope effects, with values of k(H)/k(D)=0.93 for the beta carbon and k(H)/k(D)=0.97 for the alpha carbon, which suggested an unsymmetrical transition state with stepwise O transfer. Competitive epoxidation of para-substituted styrenes revealed a linear dual-parameter Hammett plot with a slope of 1.00. Under standard conditions, epoxidation of 1 a in the presence of ten equivalents of H(2) (18)O resulted in an absence of the isotopic label in (S,S)-2 a. A positive nonlinear effect was observed during the epoxidation of 1 a in the presence of (S,S)-5 a and (R,R)-5 a.

A general gold-catalyzed direct oxidative coupling of non-activated arenes.

A gold-catalyzed mild and general oxidative homo-coupling of arenes using PhI(OAc)2 as the oxidant is described (13 examples, 31-81% yield).

Preparation of novel unsymmetrical bisindoles under solvent-free conditions: synthesis, crystal structures, and mechanistic aspects.

Indole aziridines and their hydroxyl derivatives have been used for the preparation of a small library of novel functionalized bisindoles. Diversification of these building blocks by solvent-free C-C-bond formation on solid support yielded annulated Hymenialdisine analogues under mild reaction conditions. Indoles as C-nucleophiles form potentially pharmacologically active bisindoles through an electrophilic aromatic substitution pathway in good to excellent yields. Further transformations of the indole aziridines with H-, N-, and O-nucleophiles demonstrate their versatility as key intermediates in diversity oriented synthesis. The hydroxyl precursor leads also to unsymmetrical bisindoles under similar reaction conditions. Important intermediates and final library compounds were confirmed by X-ray analysis. Theoretical studies on these systems show the possible cationic intermediate in the substitution pathway.

A general copper-catalyzed sulfonylation of arylboronic acids.

A general copper-catalyzed method for the sulfonylation of arylboronic acids with sulfinate salts is described. A variety of alkyl-aryl, diaryl, and alkyl-heteroaryl sulfones were synthesized in good yield.

A novel environmentally benign method for the selective oxidation of alcohols to aldehydes and ketones.

In the presence of [Ru(terpyridine)(2,6-pyridinedicarboxylate)], aliphatic and benzylic alcohols are oxidized to the corresponding aldehydes or ketones with high selectivity by using hydrogen peroxide as the oxidant. There is no need for the addition of co-catalysts or organic solvents. By applying an optimized reaction protocol, high catalyst productivity (turnover number>10,000) and activity (turnover frequency up to 14,800 h(-1)) has been achieved.

Development of a general and efficient iron-catalyzed epoxidation with hydrogen peroxide as oxidant.

The development of inexpensive and practical iron catalysts for the environmentally benign epoxidation of olefins with hydrogen peroxide as terminal oxidant is described. By systematic variation of ligands, metal sources, and reaction conditions, it was discovered that FeCl3 x 6 H2O in combination with pyridine-2,6-dicarboxylic acid and different amines shows high reactivity and excellent selectivity towards the epoxidation of aromatic olefins and moderate reactivity towards that of aliphatic olefins.

An efficient biomimetic Fe-catalyzed epoxidation of olefins using hydrogen peroxide.

A new, environmentally benign and practical epoxidation method was developed using inexpensive and efficient Fe catalysts. FeCl3.6H2O in combination with commercially available pyridine-2,6-dicarboxylic acid and amines showed excellent reactivity and selectivity towards aromatic olefins and moderate reactivity towards 1,3-cyclooctadiene utilizing H2O2 as the terminal oxidant.

New synthetic protocols for the preparation of unsymmetrical bisindoles.

Novel unsymmetrical bisindoles were synthesized by a solvent-free C-C bond-formation reaction under mild conditions. Starting from aziridines or hydroxyl precursors, indoles have been used as C-nucleophiles to form new pharmacologically interesting bisindoles via an electrophilic aromatic substitution pathway in good to excellent yields. [reaction: see text]

Ruthenium-catalyzed asymmetric epoxidation of olefins using H2O2, part I: synthesis of new chiral N,N,N-tridentate pybox and pyboxazine ligands and their ruthenium complexes.

The synthesis of chiral tridentate N,N,N-pyridine-2,6-bisoxazolines 3 (pybox ligands) and N,N,N-pyridine-2,6-bisoxazines 4 (pyboxazine ligands) is described in detail. These novel ligands constitute a useful toolbox for the application in asymmetric catalysis. Compounds 3 and 4 are conveniently prepared by cyclization of enantiomerically pure alpha- or beta-amino alcohols with dimethyl pyridine-2,6-dicarboximidate. The corresponding ruthenium complexes are efficient asymmetric epoxidation catalysts and have been prepared in good yield and fully characterized by spectroscopic means. Four of these ruthenium complexes have been characterized by X-ray crystallography. For the first time the molecular structure of a pyboxazine complex [2,6-bis-[(4S)-4-phenyl-5,6-dihydro-4H-[1,3]oxazinyl]pyridine](pyridine-2,6-dicarboxylate)ruthenium (S)-2 aa, is presented.

Ruthenium-catalyzed asymmetric epoxidation of olefins using H2O2, part II: catalytic activities and mechanism.

Asymmetric epoxidation of olefins with 30 % H2O2 in the presence of [Ru(pybox)(pydic)] 1 and [Ru(pyboxazine)(pydic)] 2 has been studied in detail (pybox = pyridine-2,6-bisoxazoline, pyboxazine = pyridine-2,6-bisoxazine, pydic = 2,6-pyridinedicarboxylate). 35 Ruthenium complexes with sterically and electronically different substituents have been tested in environmentally benign epoxidation reactions. Mono-, 1,1-di-, cis- and trans-1,2-di-, tri-, and tetra-substituted aromatic olefins with versatile functional groups can be epoxidized with this type of catalyst in good to excellent yields (up to 100 %) with moderate to good enantioselectivies (up to 84 % ee). Additive and solvent effects as well as the relative rate of reaction with different catalysts have been established. It is shown that the presence of weak organic acids or an electron-withdrawing group on the catalyst increases the reactivity. New insights on the reaction intermediates and reaction pathway of the ruthenium-catalyzed epoxidation are proposed on the basis of density functional theory calculation and experiments.

Synthesis of a new chiral N,N,N-tridentate pyridinebisimidazoline ligand library and its application in Ru-catalyzed asymmetric epoxidation.

A small ligand library of chiral tridentate N,N,N-pyridinebisimidazolines have been synthesized for the first time. This new class of ligands can be easily tuned and synthesized on multi g-scale. The usefulness of the ligands is shown in the ruthenium-catalyzed asymmetric epoxidation with hydrogen peroxide as oxidant. Excellent yields (>99%) and good enantioselectivities (up to 71% ee) have been obtained for the epoxidation of aromatic olefins. [reaction: see text]