Nitrenes, addition to alkenes

Aziridines are important compounds due to their versatility as synthetic intermediates. In addition, aziridine rings are present in innumerable natural products and biologically active compounds. Nitrene addition to alkenes is one of the most well established methods for the synthesis of aziridines. Photolysis or thermolysis of azides are good ways to generate nitrenes. Nitrenes can also be prepared in situ from iodosobenzene diacetate and sulfonamides or the ethoxycarbonylnitrene from the A-sulfonyloxy precursor. 

Nitrene addition to alkenes can be aided by the nse of a transition metal, such as copper, rhodium, ruthenium, iron, cobalt, etc. NHC-Cu catalysts have been used in nitrene addition. For example [Cu(DBM)(IPr)] 147 (DBM = dibenzoyl-methane) was successfully employed in the aziridination of aliphatic alkenes 144 in presence of trichloroethylsulfamate ester 145 and iodosobenzene 146 (Scheme 5.38) [43]. 

Copper(I) complexes containing NHC-phenoxyimine 153 or NHC-phenoxyamine 154 were shown to be good catalyst systems for nitrene addition to alkenes 144 (Scheme 5.40) [45]. The catalyst systems showed to be highly efficient as only 1 mol% catalyst loading was required to afford aziridines 155 in moderate to good yields. 

Scheme 5.40 Nitrene addition to alkenes catalysed by NHC-Cu complex...

Aziridine synthesis can be achieved via nitrene addition to alkenes making use of a sulfonoxycarbamate [112]. Treatment of this reagent vith potassium carbonate in the presence of an alkene together with a PTC leads to the aziridine (Eq. 3.20). The reaction time is reduced from 2-3 h to 15 min when sonication is applied. 

With respect to the intermolecular nitrene addition to alkenes, the formation of aziridines is generally observed. Nevertheless, the use of sulfonimidamides has allowed the discovery of a highly chemoselective intermolecular aUylic C(sp )-H amination that can be applied to several classes of alkenes. Various terpenes and aUyl enol carbonates, particularly, undergo allylic amination in excellent yields of up to 98% (Scheme 28). The chemoselectivity was supposed to be controlled by the substrate. Hyperconjugation of the aUylic C—H bonds with the adjacent Jt-system would increase their reactivity, a result corroborated by the exclusive formation of the aziridine from P-caryophyUene whose structure does not display such a hyperconjugative effect for the aUylic C—H bonds. 

Thus far, enantioselective intramolecular aziridination via metal nitrene intermediates has not been successful. Bromamine-T has recently been shown to be a viable source of nitrene for addition to alkenes in copper halide catalyzed reactions, " and so has iodosylbenzene (Phl=0) that forms 44 in situ. Conceptually, aziridination does not necessarily fall between cyclopropanation and epoxidation, as some have suggested. Instead, metal nitrene chemistry has unique problems and potential advantages associated with the electron pair at nitrogen that are yet to be fully overcome. 

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. 

Aziridines are readily accessible, yet under used as synthetic intermediates. There is an even greater variety of methods of preparation Aan for epoxides. Nitrene additions to congested alkenes (Section... 

A further restriction on the synthetic utility of the nitrene addition reaction is its unpredictable stereochemistry in reactions with disubstituted alkenes such as cis- and trans-but-2-ene. Nitrenes can exist in a singlet or triplet state. For most nitrenes the triplet (diradical) state is the ground state. Nitrenes that are generated thermally or by direct photolysis are initially in the singlet state and their (concerted) addition to alkenes is stereospeciflc. If the alkenes are relatively unreactive the nitrene can convert into its ground triplet state either partially or completely before addition. The resultant aziridines are produced with varying degrees of stereoselectivity because the addition of the triplet nitrene is a stepwise process. The triplet species can also be produced directly by photosensitized addition." " ... 

This nitrene is somewhat more selective than simple carbenes, showing selectivities of roughly 1 10 40 for the primary, secondary, and tertiary positions in 2-methyl-butane in insertion reactions. The relationship between nitrene multiplicity and stereospecificity in addition to alkenes is analogous to that described for carbenes. The singlet gives stereospecific addition, while the triplet gives nonstereospecific addition products. 

As another example of nitrene formation, the reaction of o-nitrostilbene (96) with CO in the presence of SnCU affords 2-phenylindole (97). The reaction is explained by nitrene formation by deoxygenation of the nitro group with CO, followed by the addition of the nitrene to alkene. Similarly, the 2//-indazole derivative 99 was prepared by reductive cyclization of the A-(2-nitrobenzyli-dene)amine 98[89]. 

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%. 

Those reactions that have found general use for the preparation of aziridines can be grouped into two broad classes addition and cyclization processes, and each of these categories can be further divided. Addition processes can be classified as being C2+N1 reactions (addition of nitrenes, or nitrene equivalents [ nitrenoids ], to alkenes Scheme 4.1) or (J N1+C1 reactions (addition of carbenes or carbenoids to imines Scheme 4.2). 

C2+N1 reactions addition of nitrenes, or nitrenoids, to alkenes Scheme 4.1... 

There are two general methods within this subcategory, involving one- or two-step mechanisms. Nitrenes and metalonitrenes thus add to alkenes by a direct azir-idination reaction, whereas nonmetallic nitrenoids usually react through an addition-elimination process (Scheme 4.6). 

Notwithstanding the drawbacks to the method, the addition of nitrenes to alkenes is a well studied classical method for direct aziridination. The original reactions (often involving alkoxycarbonylnitrenes) employed harsh conditions, resulting in nonstereoselective transformations. In these pioneering reports, the requi-... 

The synthesis of aziridines through reactions between nitrenes or nitrenoids and alkenes involves the simultaneous (though often asynchronous vide supra) formation of two new C-N bonds. The most obvious other alternative synthetic analysis would be simultaneous formation of one C-N bond and one C-C bond (Scheme 4.26). Thus, reactions between carbenes or carbene equivalents and imines comprise an increasingly useful method for aziridination. In addition to carbenes and carbenoids, ylides have also been used to effect aziridinations of imines in all classes of this reaction type the mechanism frequently involves a stepwise, addition-elimination process, rather than a synchronous bond-forming event. 

Intermolecular addition of photochemically generated nitrenes and in particular acylnitrenes to alkenes provides a useful and widely applied route to aziridines.385 An analogous intramolecular photoreaction is thought to be involved in the conversion of the o-azidophenylethylfuran 461 into the pyrrolo[l,2-a]quinoline 462 as outlined in Scheme 13,386 and intramolecular addition to an azo group has been observed in the 8-azido-1-arylazonaphthalenes 463.387... 

This property is relatively rare in the very large number of reactions for which substituent effects were evaluated quantitatively106. It seems to be common, however, for all dediazoniations of arenediazonium ions and of related compounds, e.g. of substituted phenyl azides forming nitrenes, as well as for additions of carbenes to alkenes. 

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