Stereochemical control of the Passerini reaction

A catalytic asymmetric Passerini reaction using tridentate indan (pybox) Cu(II) Lewis acid complex 4 with substrates capable of bidentate coordination has been achieved. The reaction occurs via ligand-accelerated catalysis.     

Utility of the iridium complex of the pybox ligand in regio- and enantioselective allylic substitution

The viability of the iridium complex of pybox as chiral catalyst in allylic substitutions and the enantioselective synthesis of branched products was studied. Among several chiral ligands evaluated, the iridium complex of pybox having a phenyl group catalyzed the reaction with high activity to form the branched amines with good enantioselectivities when hydroxylamine, amine, and aniline were employed as a nucleophile. The allylic substitution with oximes proceeded smoothly to give the branched oxime ethers with good enantioselectivities. [reaction: see text]     

Enantioselective Allylic Oxidation of Olefins Using Chiral Quinolinyl‐oxazoline Copper Complex Catalysts

Copper complexes of chiral quinolinyl‐oxazoline have been studied as the catalysts for enantioselective allylic oxidation of cycloalkenes with tert‐butyl perbenzoate. Using 5 mol% of these chiral catalysts, optical active allylic benzoates were obtained in moderate enantiomeric excesses. CuOTf prepared in situ, CuClO₄ and CuPF₆ were found to be good precatalysts in acetone.     

Copper-catalyzed regioselective allylic oxidation of olefins via C–H activation

A regioselective oxidation of allylic C–H bond to C–O bond catalyzed by copper (I) was developed with diacyl peroxides as oxidants. The oxidation of allylic C–H bond was accomplished with good yield and regioselectivity under mild reaction conditions. This method has a broad substrate scope including cyclic olefins, terminal and internal acyclic olefins and allyl benzene compounds. The reaction proceeds by a radical mechanism as suggested by spin trapping experiments.     

Catalytic asymmetric synthesis of secondary nitriles via stereoconvergent Negishi arylations and alkenylations of racemic α-bromonitriles

The first method for the stereoconvergent cross-coupling of racemic α-halonitriles is described, specifically, nickel-catalyzed Negishi arylations and alkenylations that furnish an array of enantioenriched α-arylnitriles and allylic nitriles, respectively. Noteworthy features of this investigation include: the highly enantioselective synthesis of α-alkyl-α-aryl nitriles that bear secondary α-alkyl substituents; the first examples of the use of alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl electrophiles; demonstration of the utility of a new family of ligands for asymmetric Negishi cross-couplings (a bidentate bis(oxazoline), rather than a tridentate pybox); in the case of arylzinc reagents, carbon-carbon bond formation at a remarkably low temperature (-78 °C), the lowest reported to date for an enantioselective cross-coupling of an alkyl electrophile; a mechanistic dichotomy between Negishi reactions of an unactivated versus an activated secondary alkyl bromide.     

Hydroxylamines as oxygen atom nucleophiles in transition-metal-catalyzed allylic substitution

[reaction: see text] The viability of hydroxylamines as nucleophiles in transition-metal-catalyzed allylic substitutions was examined. We have found that the oxygen atom of hydroxylamines having an N-electron-withdrawing substituent (also known as hydroxamic acids) acts as a reactive nucleophile. The palladium-catalyzed O-allylic substitution of hydroxylamines with allylic carbonate afforded the linear hydroxylamines. The selective formation of the branched hydroxylamines was observed in iridium-catalyzed reaction. Regio- and enantioselective allylic substitution of the unsymmetrical phosphates with hydroxylamines was studied by using the iridium complex of chiral pybox ligand. The aqueous-medium reaction with hydroxylamines proceeded smoothly in the presence of Ba(OH)(2).H(2)O to give the branched products with good enantioselectivities.     

An improved protocol for the ruthenium(pybox)-catalyzed asymmetric alkene epoxidation

A considerable rate enhancement in the ruthenium-catalyzed asymmetric epoxidation of olefins in the presence of PhI(OAc)₂ is reported. By the addition of H₂O, the rate of the reaction was increased by two orders of magnitude. Reactions of both aliphatic and aromatic olefins were realized for the first time and enantioselectivities up to 71% ee were obtained. In addition an in situ generation of ruthenium pybox catalysts for faster screening of oxidation catalysts was also developed.     

A reusable enantioselective catalytic system for the Kharasch–Sosnovsky allylic oxidation of alkenes based on a ditopic azabis(oxazoline) ligand

An easily recoverable and reusable enantioselective catalytic system based on the self-assembly of a coordination polymer through the use of a chiral ditopic ligand, is described for the allylic oxidation of cycloalkenes with tert-butyl perbenzoate. Upon addition of the substrates and a coordinating solvent (acetone or acetonitrile) the coordination polymer disassembles, allowing the catalysis to take place in homogeneous phase. After completion of the reaction, the catalyst reassembles as a coordination polymer upon solvent evaporation and addition of hexane, and is recovered as an insoluble solid. This way, good enantioselectivities and yields are obtained in seven consecutive operation cycles.     

Synthesis of new chiral 2,2'-bipyridine ligands and their application in copper-catalyzed asymmetric allylic oxidation and cyclopropanation

A series of modular bipyridine-type ligands 1 and 3-9 has been synthesized via a de novo construction of the pyridine nucleus. The chiral moieties of these ligands originate from the isoprenoid chiral pool, namely, beta-pinene (10 --> 1), 3-carene (14 --> 3 and 5), 2-carene (28 --> 4), alpha-pinene (43 --> 6-8), and dehydropregnenolone acetate (48 --> 9), respectively. Copper(I) complexes, derived from these ligands and (TfO)(2)Cu (1 mol %) upon an in situ reduction with phenylhydrazine, exhibit good enantioselectivity (up to 82% ee) and unusually high reaction rate (typicaly 30 min at room temperature) in allylic oxidation of cyclic olefins (52 --> 53). Copper-catalyzed cyclopropanation proceeded with < or =76% enantioselectivity and approximately 3:1 to 99:1 trans/cis-diastereoselectivity (54 --> 55 + 56). The level of the asymmetric induction is discussed in terms of the ligand architecture that controls the stereochemical environment of the coordinated metal.     

Enantioselective Allylic C−H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis

The enantioselective synthesis of isochroman motifs has been accomplished by palladium(II)‐catalyzed allylic C−H oxidation from terminal olefin precursors. Critical to the success of this goal was the development and utilization of a novel chiral aryl sulfoxide‐oxazoline (ArSOX) ligand. The allylic C−H oxidation reaction proceeds with the broadest scope and highest levels of asymmetric induction reported to date (avg. 92 % ee, 13 examples with greater than 90 % ee).     

Gold‐Catalyzed Asymmetric Allylic Substitution of Free Alcohols: An Enantioselective Approach to Chiral Chromans with Quaternary Stereocenters for the Synthesis of Vitamin E and Analogues

The enantioselective synthesis of α‐ and γ‐tocopherol (the most biologically active members of vitamin E family) and analogues has been accomplished employing a new enantioselective gold catalyzed intramolecular allylic alkylation reaction followed by an olefin cross‐metathesis as key steps. The methodology proved to be applicable to different olefins highlighting its potential for the synthesis of diverse libraries.     

Synthesis of 1,8- and 2,8-dihydrocycloheptapyrazol-8-one derivatives by the reactions of 3-acetyltropolone and its methyl ethers with phenylhydrazine

3-Acetyltropolone ( 1 ) reacted with phenylhydrazine to give 3-acetyltropolone phenylhydrazone ( 3 ) and 3-methyl-1-phenyl-1,8-dihydrocycloheptapyrazol-8-one ( 4 ). The former ( 3 ) cyclized to afford the latter ( 4 ). The reaction of 3-acetyl-2-methoxytropone ( 2a ) with phenylhydrazine gave 4 , 3-methyl-2-phenyl-2,8-dihydrocyclo-heptapyrazol-8-one ( 5 ), and 3-methyl-2-phenyl-2,8-dihydrocycloheptapyrazol-8-one phenylhydrazone ( 6 ). The compound ( 5 ) reacted with phenylhydrazine to afford 6 . The reaction of 7-acetyl-2-methoxytropone ( 2b ) with phenylhydrazone gave 7-acetyl-2-methoxytropone phenylhydrazone ( 7 ), 7-acetyl-2-(N′-phenylhydrazino)-tropone phenylhydrazone ( 8 ), 3-methyl-1-phenyl-1,8-dihydrocycloheptapyrazol-8-one phenylhydrazone ( 9 ), and 6 . The compound ( 7 ) was heated to afford 4 and reacted with phenylhydrazine to afford 8 and 9 . The compound ( 8 ) was also refluxed to give 9 .     

The Oxidation of Phenylhydrazine by Tyrosinase

Tyrosinase was found to catalyze the oxidation of phenylhydrazine to phenol in a reaction that did not resemble those typically performed by tyrosinase. The kinetics of this reaction was investigated by measuring the initial velocity of the formation of phenol (25 °C). The values of k _cat and K _M for the oxidation of phenylhydrazine were obtained as 11.0 s^?1 and 0.30 mM, respectively. The generation of superoxides during the oxidation of phenylhydrazine by tyrosinase was monitored by nitroblue tetrazolium (NBT) assay. In the phenylhydrazine-tyrosinase reaction, 1 mol O₂ was required for the production of 1 mol phenol and 1/6 mol superoxide. The decomposition of superoxide by superoxide dismutase enhanced the rate constant of the oxidation of phenylhydrazine. Phenol formed in the oxidation of phenylhydrazine by tyrosinase was further oxidized by tyrosinase to an o-quinone, after the oxidation of phenylhydrazine by tyrosinase was almost completed.     

A New Dimeric Copper(II) Complex of Hexyl Bis(pyrazolyl)acetate Ligand as an Efficient Catalyst for Allylic Oxidations

A new dimeric copper(II) bromide complex, [Cu(L^OHex)Br(μ-Br)]₂ (1), was prepared by a reaction of CuBr₂ with the hexyl bis(pyrazol-1-yl)acetate ligand (L^OHex) in acetonitrile solution and fully characterized in the solid state and in solution. The crystal structure of 1 was also determined: the complex is interlinked by two bridging bromide ligands and possesses terminal bromide ligands on each copper atom. The two pyrazolyl ligands in 1 coordinate with the nitrogen atoms to complete the Cu coordination sphere, resulting in a five-coordinated geometry—away from idealized trigonal bipyramidal and square pyramidal geometries—which can better be described as distorted square pyramidal, as measured by the τ and χ structural parameters. The pendant hexyloxy chain is disordered over two arrangements, with final site occupancies refined to 0.705 and 0.295. The newly synthesized complex was evaluated as a catalyst in copper-catalyzed C–H oxidation for allylic functionalization through a Kharasch–Sosnovsky reaction without any external reducing agent. Using 0.5 mol% of this catalyst, and tert-butyl peroxybenzoate (Luperox) as an oxidant, allylic benzoates were obtained with up to 90% yield. The general reaction time was only slightly decreased to 24 h but a very significant decrease in the alkene:Luperox ratio to 3:1 was achieved. These factors show relevant improvements with respect to classical Kharasch–Sosnovsky reactions in terms of rate and amount of reagents. The present study highlights the potential of copper(II) complexes containing functionalized bis(pyrazol-1-yl)acetate ligands as efficient catalysts for allylic oxidations.     

Dirhodium(II) caprolactamate: an exceptional catalyst for allylic oxidation

The oxidation of organic molecules represents a fundamentally important chemical process. Particularly important is allylic oxidation, whereby a single methylene unit is converted directly into a carbonyl group. In this communication, we report that dirhodium(II) caprolactamate [Rh2(cap)4] in combination with tert-butyl hydroperoxide (terminal oxidant) effectively catalyzes the allylic oxidation of a variety of olefins and enones. The reaction is completely selective, tolerant of air/moisture, and can be performed with as little as 0.1 mol % catalyst in minutes. A mechanistic proposal involving redox chain catalysis has been put forth, as well as evidence for the intermediacy of a higher valent dirhodium tert-butyl peroxy complex.     

Synthesis and applications of the first polyfluorous proline derivative

Starting from trans-4-hydroxy-l-proline, a polyfluorinated proline derivative having a fluorine content of 54% has been prepared. It has been tested as a catalyst in the aldol reaction between p-nitrobenzaldehyde and acetone with 73% ee in BTF and in copper(I)-catalyzed allylic oxidation of cyclohexene with 20% ee in HFIP.     

Reaction of 1,1,2,2-tetrafluoropropanal with phenylhydrazine

Conclusions The reaction of 1,1,2,2-tetrafluoropropanal with phenylhydrazine gave difluoromethyl-glyoxal bis(phenylhydrazone) and mesoxaldehyde tris(phenylhydrazone); reaction with phenylhydrazine acetate in aqueous medium gave 1-phenyl-4-phenylazopyrazole. The dehydrofluorination of perfluoroethylglyoxal bis(phenylhydrazone led to 1-phenyl-4-phenylazo-5-trifluoro-methylpyrazole.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1912–1916, August, 1977.The authors express their gratitude to P. V. Petrovskii for taking and interpreting the¹³C NMR spectra.     

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.     

Allylic amination of unfunctionalyzed olefins by nitroarenes and CO, catalyzed by Ru3(CO)12/Ph-BIAN (Ph-BIAN=bis(phenylimino)acenaphthenequinone): extension to the synthesis of allylic amines with strongly electron-withdrawing or electron-donating groups on the aryl ring

The allylic amination of unfunctionalyzed olefins by nitroarenes under CO pressure, catalyzed by Ru₃(CO)₁₂/Ph-BIAN (Ph-BIAN=bis(phenylimino)acenaphthenequinone) has been extended to some substrates with strongly electron-withdrawing groups on the nitroarene. Reaction of 1,4-dinitrobenzene selectively affords functionalization of only one nitro group, the other remaining unreacted. However, the second nitro group can be reduced in one pot by CO/H₂O in the presence of the same catalytic system employed in the amination reaction, to afford the corresponding 4-amino derivative. Some attempts to render the reaction enantioselective by employing chiral bis-oxazolines as ligands in place of Ph-BIAN are described. Bis-oxazolines are suitable ligands for the reaction, although not as efficient as Ph-BIAN, but the allylic amine obtained was found to be racemic.     

Carbohydrate-based spiro bis(isoxazolines): synthesis and evaluation in asymmetric catalysis

Two carbohydrate-based spiro bis(isoxazolines) were synthesized via 1,3-dipolar cycloaddition from peracetylated methylene exo-glucal and the corresponding bis(arylnitrile oxide). The bis(cycloadducts) were then evaluated as ligands for enantioselective catalytic reactions. The Pd-catalyzed Tsuji-Trost reaction between a malonate and an allylic acetate did not provide good results. The poor conversion observed can be attributed to the rearrangement of the ligand in the reaction mixture to afford the corresponding ring-opened isoxazole which has been characterized. Both ligands were also evaluated in Cu(I)-catalyzed asymmetric imine alkynylation and afforded the product in good yield and modest enantioselectivity.