Yields Of Aziridines Research Articles

Fe(II)‐Catalyzed Synthesis of Unactivated Aziridines (N‐H/N‐Me) from Olefins Using O‐Arylsulfonyl Hydroxylamines

AbstractIron(II) catalyzed direct N−H/N−Me aziridination of olefins using O‐arylsulfonyl hydroxylamines is described. This stereospecific, mild, economical, open‐air, operationally simple, and environmentally benign procedure afforded the high yields of aziridines in a shorter reaction time.

Elucidation of the Reaction Mechanism of C2 + N1 Aziridination from Tetracarbene Iron Catalysts.

A combined computational and experimental study was undertaken to elucidate the mechanism of catalytic C2 + N1 aziridination supported by tetracarbene iron complexes. Three specific aspects of the catalytic cycle were addressed. First, how do organic azides react with different iron catalysts and why are alkyl azides ineffective for some catalysts? Computation of the catalytic pathway using density functional theory (DFT) revealed that an alkyl azide needs to overcome a higher activation barrier than an aryl azide to form an iron imide, and the activation barrier with the first-generation catalyst is higher than the activation barrier with the second-generation variant. Second, does the aziridination from the imide complex proceed through an open-chain radical intermediate that can change stereochemistry or, instead, via an azametallacyclobutane intermediate that retains stereochemistry? DFT calculations show that the formation of aziridine proceeds via the open-chain radical intermediate, which qualitatively explains the formation of both aziridine diastereomers as seen in experiments. Third, how can the formation of the side product, a metallotetrazene, be prevented, which would improve the yield of aziridine at lower alkene loading? DFT and experimental results demonstrate that sterically bulky organic azides prohibit formation of the metallotetrazene and, thus, allow lower alkene loading for effective catalysis. These multiple insights of different aspects of the catalytic cycle are critical for developing improved catalysts for C2 + N1 aziridination.

Seeking Passe-Partout in the Catalytic Asymmetric Aziridination of Imines: Evolving Toward Substrate Generality for a Single Chemzyme

The asymmetric catalytic aziridination reaction (AZ reaction) of imines derived from dianisylmethyl (DAM) amine and tetra-methyldianisylmethyl (MEDAM) amine were examined with boroxinate catalysts prepared from both the VANOL and VAPOL ligands. This included an evaluation of different protocols for the preparation of the catalyst. The AZ reaction of DAM and MEDAM imines prepared from nine different aryl and aliphatic aldehydes were examined. The MEDAM imines were superior to the DAM imines in the AZ reaction, giving much higher asymmetric inductions and higher overall yields of aziridines. The MEDAM imines were found to also be superior to the previously studied diphenylmethyl (benzhydryl or Bh) and tetra-tert-butyldianisylmethyl (BUDAM) imines especially for imines derived from aliphatic aldehydes. The average asymmetric induction over the nine different MEDAM imines studied was 97% ee with the VAPOL catalyst and 96% ee with the VANOL catalyst. The MEDAM imines can be deprotected to give N-H aziridines in all cases except for some electron-rich aryl aldehydes. The MEDAM imines are much more reactive than benzhydryl imines, and this was most evident when a diazoacetate ester is replaced by a diazoacetamide. The less reactive diazoacetamides give very low yields in their reactions with benzhydryl imines but high yields with MEDAM imines.

Catalyzed addition of diazoacetoacetates to imines: synthesis of highly functionalized aziridines

The addition of diazoacetoacetates to aromatic imines derived from p-methoxyaniline is achieved using dirhodium tetraacetate as the catalyst. Highly functionalized aziridines are obtained in good yield and with excellent stereoselectivity. 2-Diazo-1,3-diketones also provide good yields of aziridines, but dimethyl diazomalonate is inactive in the transformation. The diazoacetoacetates of chiral alcohols are also examined in the reaction and moderate diastereoselectivity is achieved with (R)-pantolactone-derived diazoacetoacetate. A reaction mechanism through metal-carbene and azomethine ylide is proposed.

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.

A Practical, Fast, and High-Yielding Aziridination Procedure Using Simple Cu(II) Complexes Containing N-Donor Pyridine-Based Ligands

Four-coordinate dichlorocopper(II) complexes derived from di(2-pyridyl)methanes or pyridine itself exhibit high catalytic activity in aziridination of regular olefins with PhINTs in weakly coordinating chloroform in the presence of 1-2 equiv of NaBArF4 (BArF4- = tetra[3,5-di(trifluoromethyl)phenyl]borate). High yields of aziridines exceeding 90% can be obtained with a 1:1 olefin/PhINTs ratio and 1-5 mol % catalyst loading for such reactive olefins as styrene, tri- and tetramethylethylene. For cis-cyclooctene, indene, methyl acrylate, methyl methacrylate, vinyl methyl ketone, tert-butylethylene, and neopentylethylene, as well as for 1-hexene and cyclopentene, yields of corresponding aziridines vary from 44% to 83%. The catalytic activity and efficiency of the reported copper complexes decrease moderately in the absence of NaBArF4.

Copper‐Homoscorpionate Complexes as Very Active Catalysts for the Olefin Aziridination Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic asymmetric heterogeneous aziridination of styrene using Cu2+-exchanged zeolite Y: effect of the counter-cation on enantioselectivity and on the reaction profile

Effective catalysts have Cu2+-exchange levels of ca. 40–60% of the maximum concentration for electroneutrality and, consequently, Cu-zeolite Y catalysts contain an additional counter-cation (H+, Li+, Na+, K+, Rb+, Cs+) whose effect is explored. With Li+, Na+, K+ counter-cations, the zeolite structure is not markedly affected but, with Rb+ and Cs+, there is some loss of crystallinity. Replacement of H+ by group I cations does not markedly influence the overall ee observed for aziridine indicating that the presence of protons in the Cu-HY catalysts are not detrimental to the reaction. Catalysts containing group I cations typically give decreased leaching of Cu2+ during the reaction. At low nitrene donor to styrene molar ratios (1∶1), replacement of H+ by group I cations leads to a small enhancement in the ee of aziridine, although the yield of aziridine formed is decreased under all reaction condition. At higher molar ratios of nitrene donor to styrene, the ee is suppressed, particularly with Rb and Cs. The effect of reaction time on aziridine yield reveals a reaction profile in which the reaction initially proceeds rapidly, then slows down prior to accelerating again in the latter part of the reaction. This effect is accentuated by increasing the size of the counter-cation. This reaction profile is also observed for the homogeneously catalysed pathway and, consequently, it cannot be due solely to a confinement effect within the zeolite pores. Over addition of reaction by-products (NsNH2, PhI) accentuates the shape of this reaction profile and the effect is discussed in terms of the interactions of such molecules at the active site.

Copper-Homoscorpionate Complexes as Very Active Catalysts for the Olefin Aziridination Reaction

A series of complexes TpxCu (Tpx = homoscorpionate ligand) have been tested as the catalysts for the olefin aziridination reaction using PhINTs as the nitrene source. Very high yields of aziridines have been obtained with a group of representative substrates, including nonactivated terminal olefins. The high activity of these catalysts has allowed the use of equimolar amounts of PhINTs and olefins, avoiding the requirement of excess olefin. In an effort to eliminate nondesired byproducts, chloramine-T has been employed as the nitrene source, in a reaction that produces sodium chloride as the sole residue, with high degrees of conversions also being obtained.

Aziridination of β-substituted styrene derivatives with 3-acetoxyaminoquinazolin-4(3H)-ones: probing transition state geometry from changes in diastereoselectivity

Reaction of (S)-3-acetoxyamino-2-[1-(t-butyldimethylsilyloxy)ethyl]quinazolin-4(3H)-one 5 (Q1NHOAc) with styrene and R(β)-substituted E-styrenes (R = SiMe3, Me, CH2Cl, CHCl2) gives the corresponding aziridines diastereoselectively. The diastereoselectivity increases in the same sense from 5 ∶ 1 → 20 ∶ 1 as the electron-withdrawing character of R increases [H(Me), CH2Cl, CHCl2] but is accompanied by a decrease in yield of aziridine. A similar increase in diastereoselectivity is found in the reaction of 3-acetoxyamino-2-(2,3,3-trimethylpropyl)quinazolin-4(3H)-one 38 (Q4NHOAc) with the same β-substituted styrenes.An explanation for these observations is offered based on a tighter, more symmetrical transition state for the aziridination of styrenes bearing the more electron-withdrawing β-substituents and is supported by SCF calculations.

Heterogeneous catalytic aziridination of styrene using transition-metal-exchanged zeolite Y

Transition-metal-exchanged zeolite Y (Cr, Mn, Fe, Co, Ni, Cu, Zn) are compared as catalysts for the aziridination of styrene using (N-(p-tolylsulfonyl)imino)phenyliodinane (PhI=NTs) as the nitrene precursor. The Cu-exchanged zeolite shows high levels of aziridine formation, but significant yields of aziridine are also obtained with the Cr-, Mn-, Fe- and Co-exchanged zeolite Y. In contrast, these cations produce much lower yields of aziridine in the corresponding homogeneously catalysed reactions. Addition of a chiral bis-oxazoline ligand leads to a significant decrease in the yield of aziridine for all the ion-exchanged zeolites, with the exception of the Cu-exchanged zeolite Y. Further experiments with (N-(p-nitrophenylsulfonyl)imino)phenyliodinane (PhI=NNs) as nitrene donor indicate that, in addition to Cu-exchanged zeolite Y, significant yields of the aziridine can be formed for Zn-, Mn-, Fe- and Co-exchanged zeolite Y. The major by-product was benzaldehyde, probably formed by oxidation of styrene. These data confirm that Cu-exchanged zeolite Y is the best aziridination catalyst but it is shown that other metal-exchanged zeolites are also catalytically active.

Catalytic asymmetric heterogeneous aziridination of styrene using CuHY: effect of nitrene donor on enantioselectivity

The copper-catalysed aziridination of styrene with copper-exchanged zeolite Y (CuHY) and copper(II) triflate (trifluoromethanesulfonate) (Cu(OTf)2) as catalysts is described in detail. Two nitrene donors, [N-(p-tolylsulfonyl)imino)]phenyliodinane (PhINTs) and [N-(p-nitrophenylsulfonyl)imino]phenyliodinane (PhINNs) are compared. Modification of the catalyst with bis(oxazolines) affords enantioselective catalysts and a range of chiral bis(oxazolines) has been studied. The ratio of nitrene donor to styrene is shown to be an important factor controlling both the yield and ee of aziridine formed. The best results are obtained with PhINNs; ee, ≥ 90%, together with high yields (≥ 85%), can readily be achieved with this nitrene donor using acetonitrile as solvent. Addition of the nitrene donor over a period of time, rather than all at the start of the reaction, is shown to enhance the yield of the aziridine but the ee is significantly decreased for both the homogeneous and the heterogeneous catalysts. Experiments in which the breakdown products of the nitrene donor, iodobenzene and the corresponding sulfonamide, are added at the start of the reaction show that a complex interplay exists at the copper active site between the reactants, products, chiral modifier and the solvent. However, the heterogeneous catalyst, CuHY, is found to give enhanced enantioselection for a range of bis(oxazolines) compared to the homogeneous catalyst, and the effect is considered to be due to the confinement of the catalyst within the micropores of the zeolite.

Aziridination of alkenes with 3-acetoxyaminoquinazolinones in the presence of hexamethyldisilazane

Yields of aziridines from reaction of some alkenes, including α,β-unsaturated esters, with 3-acetoxyamino-2-isopropylquinazolinone 6 (Q3NHOAc) are greatly increased in the presence of hexamethyldisilazane (HMDS). A mono-aziridination product of naphthalene is obtained only in the presence of HMDS. It is concluded that the enhanced yields in these aziridinations are the result of scavenging of acetic acid by HMDS, thus prolonging the lifetime of the aziridinating agent Q3NHOAc.

Chiral aziridination of α,β-unsaturated esters and ketones using N-nitrenes in the presence of trifluoroacetic acid

Aziridination of various α,β-unsaturated esters and α,β-unsaturated ketones has been studied using the N-nitrene generated by oxidation of 3-amino-2-(1,2,2-trimethylpropyl)quinazolin-4(3H)-one (1) with lead tetra-acetate in dichloromethane at room temperature. The stereoselectivity of this aziridination is greatly increased by the addition of trifluoroacetic acid before the oxidation of the aminoquinazolinone (1). The presence of trifluoroacetic acid has two additional advantages in these aziridinations: (a) it allows the reaction to be carried out at –60 °C with the expected increase in stereoselectivity; and (b) the alkene can be used in molar equivalent amounts with little loss of yield of aziridine. For example, aziridination of methyl acrylate (1.1 mol equiv.) at –60 °C with the N-nitrene derived from compound (1)(1 mol equiv.) gave the aziridine stereoisomers (5)(ratio 23:1) in 65% isolated yield.

Kinetics and Mechanism of Aziridine Synthesis from Ketoxime with Lithium Aluminum Hydride

Abstract The stoichiometry and rate of the reaction of dibenzyl ketoxime (1) with lithium aluminum hydride in tetrahydrofuran leading to cis-2-benzyl-3-phenylaziridine (2, 92%) and 2-amino-1,3-diphenylpropane (3, 8%) were determined by gas meter and vpc. It was found that the aziridine formation proceeds with an immediate evolution of 1 mole of hydrogen followed by a slow liberation of a second mole of hydrogen and an accommodation of 1 equiv. of hydride into the molecule. Also, the formation has an induction period and there is a catalytic acceleration effect by the concurrently-formed minor product 3. Combination of the previously-reported results and the present findings leads us to propose a mechanism by which an aluminum derivative rapidly obtained on addition of 1 to the solution of lithium aluminum hydride undergoes slow hydrogen elimination to afford an azirine intermediate, followed by reduction to the aziridine. Making use of the catalytic effect discovered, the reaction rate and yield of aziridine were increased by the addition to the reaction mixture of an amine, particularly a secondary amine such as n-butylmethylamine.