Aziridines with nitrenes

Apart from cyclopropenation, catalytic aziridination with nitrene transfer to olefins is generally considered an analogue reaction of metal-catalyzed carbene-transferred cyclopropanation. Aziridination and cyclopropanation are proposed to share fundamental mechanistic features. Many of the catalysts that were successfully applied in aziridination are also efficient catalysts for cyclopropanation. For... 

Aziridines have been prepared stereospecifically by the nucleophilic addition of the nitrogen residue to alkenes <80T73). Introduction of the nitrene is accomplished readily via a Michael-type addition with free diphenylsulfilimine (Scheme 12), and where a chiral sulfilimine is used the chirality is transferred to the aziridine with optical yields in excess of 25%. 

One interesting effect observed in these aziridination reactions was the increase in percentage ee with reaction time, both in homogeneous and heterogeneous phases [66]. The origin of this effect was thoroughly studied in a series of experiments that demonstrated that the aziridine products were able to react with sulfonamide byproducts and with nitrene donors, in the... 

A more practical, atom-economic and environmentally benign aziridination protocol is the use of chloramine-T or bromamine-T as nitrene source, which leads to NaCl or NaBr as the sole reaction by-product. In 2001, Gross reported an iron corrole catalyzed aziridination of styrenes with chloramine-T [83]. With iron corrole as catalyst, the aziridination can be performed rmder air atmosphere conditions, affording aziridines in moderate product yields (48-60%). In 2004, Zhang described an aziridination with bromamine-T as nitrene source and [Fe(TTP)Cl] as catalyst [84]. This catalytic system is effective for a variety of alkenes, including aromatic, aliphatic, cyclic, and acyclic alkenes, as well as cx,p-unsaturated esters (Scheme 28). Moderate to low stereoselectivities for 1,2-disubstituted alkenes were observed indicating the involvement of radical intermediate. 

Investigations into the mechanism of this reaction revealed several interesting facts (61). Compelling evidence was presented that a discreet Cu nitrenoid was involved in the catalytic cycle. Photolysis of a solution of tosyl azide and styrene in the presence of the catalyst afforded aziridine with the same enantioselectivity as obtained from the PhI=NTs reaction, Eq. 69. Since photolysis of tosyl azide is known to extrude dinitrogen and form the free nitrene, the authors argue that this is indicative of a common Cu-nitrenoid intermediate in this reaction. 

Evans et al. proposed that an imino-copper species in the 3+ oxidation state (Cu3+=NTs) should be the key intermediate in copper-catalyzed aziridinations [75b]. This proposal was supported by Jacobsen s study on the dependence of enantioselectivity on the nitrene precursors and/or the substrate structures with two iminoiodoarenes, PhI=NTs and 2,3,4-Me3-6-(r-Bu)C6HI=NTs), in the presence of CuPF6-33a complex and four olefins [80b]. This study disclosed that enantioselectivity did not depend on the iminoiodoarene, but on the olefins used, that is, the finding excludes the possibility that a Cu-Arl=NTs adduct is a key intermediate. It has also been observed that the photochemical aziridination with tosyl azide (TsN3) catalyzed... 

For the aziridination of 1,3-dienes, copper catalysis gave better yields of A-tosyl-2-alkenyl aziridines with 1,3-cyclooctadiene, 1,4-addition occurred exclusively (50%) [46]. Good results were also obtained on rhodium catalysed decomposition of PhI=NNs (Ns = p-nitrophenylsulphonyl) with some alkenes the aziridination was stereospecific, whereas with chiral catalysts asymmetric induction (up to 73% ee) was achieved. However, cyclohexene gave predominantly (70%) a product derived from nitrene insertion into an allylic carbon-hydrogen bond [47]. 

To demonstrate that alternative types of silicate framework can be used for this reaction, experiments were carried out with copper-exchanged MCM-41. Yields of up to 87% of the aziridine with e.e. of 37% were obtained using PhI=NTs as the nitrene donor. Using... 

This review is written to cover the needs of synthetic chemists with interests in oxidizing alkenes by addition of nitrogenous substituents. Whilst some aspects have been covered in previous reviews (noted in the text), most notably in the Tetrahedron Report No. 144, Amination of Alkenes and prior reviews on aziridines and nitrenes, the present review is the fust conq>ilation of references to the whole range of these particular bond-forming processes. A review by Whitham provides a useful general introduction to reaction mechanisms of additions to alkenes in greater detail than can be covered here. The oxidation requirement excludes from the scope the additions of N H and most additions of N + Metal or N + C. Hence, unmodified Michael and Ritter reactions are excluded. These topics are mostly covered in Volume 4 of the present series. 

The reaction of azides with 1,3-dienes affords vinyl aziridines (through nitrene or azide cycloaddition), which can be converted to dihydropyrroles. It is also possible that dihydropyrroles are directly produced from azidodienes. 

The thermal decomposition of 2-azidobenzothiophene in benzene at room temperature in the presence of (Z)- or ( )-2-butene afforded the corresponding aziridine with complete retention of the double bond configuration, supporting the hypothesis of a singlet nitrene intermediate72. However, the yields were low, since 4-cyanothiochromans were the major products. The formation of the aziridines was favored by electron-poor alkenes and by a decrease in the reaction temperature, but partial loss of the alkene configuration is observed 73. In the case of... 

Irradiation of 26 in cyclohexane solution containing either cis- or trans-4-methyl-2-pentene forms aziridines with complete (>98%) retention of olefin stereochemistry.Stereospecific aziridine formation is usually considered as evidence of a concerted, singlet nitrene addition reaction. 

Preparation.—Direct Insertion. The oxidation of 2,4-dinitrobenzenesuiphen-amide with [Pb(OAc)4] in CH2CI2 generates a nitrene which, in the presence of alkenes, gives aziridines. With /ra 5-l-phenylpropene, [200 R = 2,4-(N02)2C6H3] (64%) was formed, which could be reduced with NaBH4 to (200 R = H) (56%). Nitrenes produced by the oxidation of A(-aminophthalimide or 3-amino-2-methyl-4-quinazoline with [Pb(OAc)4] yield 6-azabicyclo[3.1.0]-hexanes, e.g. (201), in the presence of variously substituted cyclopentenes. 

Sidewall functionalization of SWCNTs can be achieved by the method of addition of reactive alkyloxycarbonyl nitrenes obtained from alkoxycarbo-nyl azides. Nitrenes attack the nanotube sidewalls in a [2 -i-1] cycloaddition by the way of thermally induced Nj-extrusion, and form an aziridine ring at the nanotube s sidewalls. Nitrene additions led to considerable amount in an organic solvent. The highest solubility of 1.2 mg/mL was achieved for SWCNT adducts with nitrenes containing crown ethers of oligoethylene glycol moieties in DMSO and TCE. The electronic properties of SWCNTs were mostly retained after functionalization, which revealed about 2 wt% functional groups were added onto the carbon nanotube sidewalls. ... 

The direct copper-catalyzed iodosyl-mediated nitrogen transfer to olefins compares with the parent rhodium-catalyzed process that is made possible by the combination of iodosylbenzene diacetate, magnesium oxide, and sulfamates. Other recent promising nitrene transfer methods involve the bromine-catalyzed aziridination of olefins using chloramine-T and the direct electrochemical aziridination with TV aminophthalimide. ... 

Other potential synthetic routes to these unsaturated aziridine derivatives which involve the addition of nitrenes to allenes <75JOC224), carbenes to imines with subsequent hydrolysis <67JA362), and of carbenoid species to ketenimines <76TL1317,79TL559) have been investigated but are collectively of little or no preparative value. 

Asymmetric aziridination of a,P-unsaturated esters by use of N-nitrenes was studied in great detail by Atkinson and co-workers [34, 35]. Here, lead tetraacetate-mediated oxidative addition of N-aminoquinazolone 30 (Scheme 3.10) to a-methy-lene-y-butyrolactone 32 was reported to proceed with complete asymmetric indue-... 

In 1999, Bob Atkinson wrote [1] that aziridination reactions were epoxida-tion s poor relation , and this was undoubtedly true at that time the scope of the synthetic methods available for preparation of aziridines was rather narrow when compared to the diversity of the procedures used for the preparation of the analogous oxygenated heterocycles. The preparation of aziridines has formed the basis of several reviews [2] and the reader is directed towards those works for a comprehensive analysis of the area this chapter presents a concise overview of classical methods and focuses on modern advances in the area of aziridine synthesis, with particular attention to stereoselective reactions between nitrenes and al-kenes on the one hand, and carbenes and imines on the other. 

When unacylated azides are used as nitrene precursors, the first reaction with an alkene is a cydoaddition, generating the corresponding 1,2,3-triazoline, which often eliminates N2 under the fierce reaction conditions to give an aziridine product (Scheme 4.9 ). 

In many instances, however, the intermediate triazoline can be isolated and separately converted into the aziridine, often with poor stereoselectivity. The first practical modification to the original reaction conditions generated the (presumed) nitrenes by in situ oxidation of hydrazine derivatives. Thus, Atkinson and Rees prepared a range of N-amino aziridine derivatives by treatment of N-aminophthali-mides (and other N-aminoheterocydes) with alkenes in the presence of lead tetraacetate (Scheme 4.10) [7]. 

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