Brønsted acid-promoted aziridination of electron-deficient olefins

A combined theoretical and experimental approach was used to systematically study the Brønsted acid-promoted aziridination of electron-deficient olefins. It was found that Brønsted acid-promoted aziridination of electron-deficient olefins proceeded through the attack of the internal nitrogen of the azide to the terminal carbon of protonated olefin, which afforded an acyclic adduct that subsequently discharged N₂ to produce the aziridine ring. The basicity of the electron-deficient olefins is an important parameter to determine the efficiency of Brønsted acid-promoted aziridination. More basic carbonyl compounds including vinyl ketones and acrylamides were predicted to be readily activated by Brønsted acid such as TfOH, whereas less basic carbonyl compounds were predicted to be poor substrates. Significantly, all these theoretical predictions were demonstrated to be consistent with the experimental data. Furthermore, a systematic evaluation of TfOH-promoted aziridination of acrylamides was performed, which established a new, single-step method for the preparation of a number of aziridine-2-carboxamides.     

Cobalt-catalyzed asymmetric olefin aziridination with diphenylphosphoryl azide

The cobalt(II) complexes of D2-symmetric chiral porphyrins, such as 3,5-Di(t)Bu-ChenPhyrin P5, can catalyze asymmetric olefin aziridination with diphenylphosphoryl azide (DPPA) as a nitrene source. Acceptable asymmetric inductions were observed for the [Co(P5)]-based catalytic system, forming the desired N-phosphorus-substituted aziridines in moderate to high yields and good enantioselectivities.     

A unique and highly efficient method for catalytic olefin aziridination

A facile, high yielding, and stereospecific method for olefin aziridination is described. This process capitalizes on the unique reactivity of sulfamate esters in combination with 1-2 mol % Rh2(tfacam)4 and PhI(OAc)2 as the terminal oxidant to promote N-atom transfer reactions. A range of structurally and electronically disparate alkenes are found to react under conditions that employ substrate as the limiting reagent and only a slight excess of H2NSO3CH2CCl3 as the nitrogen source. The product alkoxysulfonyl aziridines are useful intermediates that react smoothly with nucleophiles to generate 1,2-amine derivatives. Following aziridine ring-opening, the N-trichloroethoxysulfonyl group can be removed under mild reductive conditions (Zn(Cu)/AcOH-MeOH) to give the corresponding 1 degrees amine. The efficient and convenient performance of this chemistry should establish it as a useful tool for synthesis.     

Practical olefin aziridination with a broad substrate scope.

The present study illustrates the possibility of a rational approach that bypasses the requirement for stoichiometric amounts of toxic oxidants and metal additives (including reagents and catalysts) in organic redox reactions. We describe an aziridination process that delivers a nitrene functionality to olefins from a readily available N-aminophthalimide. Remarkably, both electron-rich and electron-poor olefins are converted to aziridines with high efficiency. The continuum of applied potentials and the heterogeneous nature of reactions at electrode surfaces allow for the electrochemical discrimination of substrates which have similar redox potentials and therefore cannot be selectively reduced or oxidized using soluble reagents. This selectivity is due to the phenomenon of overpotential, the kinetic inhibition of electron transfer on a particular electrode surface.     

Angular ligand constraint yields an improved olefin aziridination catalyst

[reaction: see text] The use of a pyridinophane, a macrocycle composed of three pyridines linked, via all ortho positions through CH(2) or CH(2)CH(2) groups, bound to copper, gives good performance (rate and yield) catalyzing the conversion of substituted aliphatic olefins and PhINTs to aziridines. Advantages also derive from using CH(2)Cl(2) solvent and the weakly coordinating anions BAr(4)(-) (Ar = C(6)H(5) or 3,5-C(6)H(3)(CF(3))(2)). Reactions are complete in minutes at 20 degrees C, and yields are almost quantitative for olefins not bearing secondary allylic CH bonds; however, cis-cyclooctene gives only the aziridine despite the allylic hydrogens.     

Non-heme iron(II) complexes are efficient olefin aziridination catalysts

Iron(II) complexes of polydentate nitrogen donor ligands catalyze the rapid aziridination of olefins by PhINTs.     

Copper-nitrenoid formation and transfer in catalytic olefin aziridination utilizing chelating 2-pyridylsulfonyl moieties

We have developed an efficient protocol for copper-catalyzed olefin aziridination using 5-methyl-2-pyridinesulfonamide or 2-pyridinesulfonyl azide as the nitrenoid source. The presence of a 2-pyridyl group significantly facilitates aziridination, suggesting that the reaction is driven by the favorable formation of a pyridyl-coordinated nitrenoid intermediate. Using this chelation-assisted strategy, synthetically acceptable yields of aziridines could be obtained with a range of aryl olefins even in the absence of external ligands. Importantly, a large excess of olefin is not required. X-ray crystallography, ESI-MS, Hammett plot analysis, kinetic studies, and computational undertakings strongly support that the observed aziridination is driven by internal coordination.     

Metal-free synthesis of 1,2-amino alcohols by one-pot olefin aziridination and acid ring-opening

A one-pot, two-step reaction comprising olefin aziridination and ring-opening of an aziridine intermediate to synthesize 1,2-amino alcohols has been developed. This reaction is suitable for several types of olefin. This methodology allows an efficient and highly stereoselective approach to various 1,2-amino alcohols, readily providing an alternative route to conventional vicinal amino alcohols.     

A highly effective cobalt catalyst for olefin aziridination with azides: hydrogen bonding guided catalyst design

[Co(P1)], which was designed on the basis of potential hydrogen-bonding interactions in the metal-nitrene intermediate, is a highly active aziridination catalyst with azides. [Co(P1)] can effectively aziridinate various aromatic olefins with arylsulfonyl azides under mild conditions, forming sulfonylated aziridines in excellent yields. The Co-based system enjoys several attributes associated with the relatively low cost of cobalt and the wide accessibility of arylsulfonyl azides. Furthermore, it generates stable dinitrogen as the only byproduct.     

The radical mechanism of cobalt(II) porphyrin-catalyzed olefin aziridination and the importance of cooperative H-bonding

The mechanism of cobalt(II) porphyrin-mediated aziridination of styrene with PhSO(2)N(3) was studied by means of DFT calculations. The computations clearly indicate the involvement of a cobalt 'nitrene radical' intermediate in the Co(II)(por)-catalyzed alkene aziridination. The addition of styrene to this species proceeds in a stepwise fashion via radical addition of the 'nitrene radical'C to the C=C double bond of styrene to form a γ-alkyl radical intermediate D. The thus formed tri-radical species D easily collapses in an almost barrierless ring closure reaction (TS3) to form the aziridine, thereby regenerating the cobalt(II) porphyrin catalyst. The radical addition of the 'nitrene radical'C to the olefin (TS2) proceeds with a comparable barrier as its formation (TS1), thus providing a good explanation for the first order kinetics in both substrates and the catalyst observed experimentally. Formation of C is clearly accelerated by stabilization of C and TS1 via hydrogen bonding between the S=O and N-H units. The computed radical-type mechanism agrees well with all available mechanistic and kinetic information. The computed free energy profile readily explains the superior performance of the Co(II)(porAmide) system with H-bond donor functionalities over the non-functionalized Co(TPP).     

Asymmetric olefin aziridination using a newly designed Ru(CO)(salen) complex as the catalyst

Highly enantioselective and good to high-yielding aziridination of conjugated and non-conjugated terminal olefins and cyclic olefins was achieved using a newly designed Ru(CO)(salen) complex as the catalyst in the presence of SESN(3) under mild conditions.     

Syntheses of acetonitrile ligated copper complexes with perfluoroalkoxy aluminate as counter anion and their catalytic application for olefin aziridination

Acetonitrile ligated copper complexes with perfluoroalkoxy aluminate as weakly coordinating counter anion are successfully synthesized. Aziridination of various olefins with PhINTs catalyzed by copper(II) complex [Cu(II)(NCCH₃)₆][Al{OC(CF₃)₃}₄]₂ affords good to excellent yields (up to 96%) and very high turnover frequency (higher than 5000 h⁻¹) under mild conditions.     

Copper(II) complexes of pyridyl-appended diazacycloalkanes: synthesis, characterization, and application to catalytic olefin aziridination

As part of an ongoing effort to rationally design new copper catalysts for olefin aziridination, a family of copper(II) complexes derived from new tetradentate macrocyclic ligands are synthesized, characterized both in the solid state and in solution, and screened for catalytic nitrene transfer reactivity with a representative set of olefins. The pyridylmethyl-appended diazacycloalkane ligands L6(py)2, L7(py)2, and L8(py)2 are prepared by alkylation of the appropriate diazacycloalkane (piperazine, homopiperazine, or diazacyclooctane) with picolyl chloride in the presence of triethylamine. The ligands are metalated with Cu(ClO4)(2).6H2O to provide the complexes [(L6(py)2)Cu(OClO3)]ClO4 (1), [(L7(py)2)Cu(OClO3)]ClO4 (2), and [(L8(py)2)Cu](ClO4)2 (3), which, after metathesis with NH4PF6 in CH3CN, afford [(L6(py)2)Cu(CH3CN)](PF6)2 (4), [(L7(py)2)Cu(CH3CN)](PF6)2 (5), and [(L8(py)2)Cu](PF6)2 (6). All six complexes are characterized by X-ray crystallography, which reveals that complexes supported by L6(py)2 and L7(py)2 (1, 2, 4, 5) adopt square-pyramidal geometries, while complexes 3 and 6, ligated by L8(py)2 feature tetracoordinate, distorted-square-planar copper ions. Tetragonal geometries in solution and d(x2 - y2), ground states are confirmed for the complexes by a combination of UV-visible and EPR spectroscopies. The divergent flexibility of the three supporting ligands influences the Cu(II)/Cu(I) redox potentials within the family, such that the complexes supported by the larger ligands L7(py)2 and L8(py)2 (5 and 6) exhibit quasi-reversible electron transfer processes (E1/2 approximately -0.2 V vs Ag/AgCl), while the complex supported by L6(py)2 (4), which imposes a rigid tetragonal geometry upon the central copper(II) ion, is irreversibly reduced in CH3CN solution. Complexes 4-6 are efficient catalysts (in 5 mol % amounts) for the aziridination of styrene with the iodinane PhINTs (in 80-90% yields vs PhINTs), while only 4 exhibits significant catalytic nitrene transfer reactivity with 1-hexene and cyclooctene.     

A novel example of chiral counteranion induced enantioselective metal catalysis: the importance of ion-pairing in copper-catalyzed olefin aziridination and cyclopropanation

A new ion-pairing route to achieve asymmetric catalysis has been observed in the copper-catalyzed aziridination of styrene with a chiral counteranion. Structural studies suggest that enantioinduction occurs via ion-pairing of the cationic copper catalyst in the chiral pocket created by the anion. The degree of asymmetric induction can be tuned with features that affect ion-pairing, such as achiral and chiral ligands, temperature, and solvent polarity.     

Copper(II) complexes incorporating poly/perfluorinated alkoxyaluminate-type weakly coordinating anions: syntheses, characterization and catalytic application in stereoselective olefin aziridination

The synthesis and characterization of a series of cationic copper(II) complexes of the type [Cu(NCR)(6)][Al(OC(CF(3))(2)R')(4)](2) (R = CH(3), Ph; R' = CF(3), Ph, PhCH(3)), incorporating poly/perfluoronated alkoxyaluminates as weakly coordinating anions (WCAs) is presented. Aziridination of various olefins, such as the unreactive olefins e.g. ethylhex-2-enoate and 1-decene, with N-tosyliminophenyliodinane catalyzed by [Cu(NCR)(6)][Al(OC(CF(3))(2)R')(4)](2) affords very good yields (up to 96%) and high TOFs (up to 5000 h(-1)) under mild conditions. Using disubstituted olefins as substrates, high stereoselectivities are obtained at room temperature. The to date highest cis?:?trans ratio (98?:?2) of the obtained aziridines is achieved for cis-stilbene in good yield (85%) as well as promising TOF (> 2000 h(-1)). The investigation of the solvent effect on yield and selectivity reveals that for certain oleophilic substrates (1-decene), less polar solvents, such as dichloromethane are a better choice than acetonitrile, which is commonly considered as the best solvent for olefin aziridination. Accordingly, a mechanism involving a paramagnetic copper nitrene intermediate with both concerted and stepwise pathways is proposed.     

Selective aziridination of olefinic esters

Summary Oxidation of 3-amino-2-isobutylquinazoline-4-one (2) with lead tetraacetate at –20°C gave N-acetoxyamino-2-isobutylquinazolin-4-one (3), which selectively aziridinated olefinic esters to yield substituted 1-(2-isobutylquinazolin-4-one-3-yl)-aziridine-2-carboxylates5a–q.

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Selektive Aziridinierung von olefinischen Estern

Zusammenfassung Oxidation von 3-Amino-2-isobutylchinazolin-4-on (2) mit Bleitetraacetat bei –20°C ergab N-Acetoxyamino-2-isobutylchinazolin-4-on (3), welches mit verschiedenen olefinischen Estern selektiv substituierte 1-(2-Isobutylchinazolin-4-on-3-yl)-aziridin-2-carbonsäureester5a–q lieferte.

     

Cobalt-catalyzed efficient aziridination of alkenes

[reaction: see text]. Cobalt porphyrins are capable of catalyzing the aziridination of alkenes with bromamine-T as the nitrene source. Among cobalt complexes of different porphyrins, Co(TDClPP) is an effective catalyst that can aziridinate a wide variety of alkenes. The catalytic system can operate at room temperature in a one-pot fashion with alkenes as limiting reagents, forming the desired N-sulfonylated aziridine derivatives in high to excellent yields with NaBr as the byproduct.