Nitrene addition reactions

The outcome of the nitrene addition reaction depends on the type of 7i-bond involved. In contrast to electron deficient olefins [26] and nonpolar olefins forming aziridines, electron rich olefins react with alkoxycarbonyl nitrenes to give oxazolines (Sch. 14) [22]. The same type of cycloaddition reaction leading to the production of five-membered rings has also been observed with nitriles [27] (such as compound 35 in Sch. 14) and isocyanates [28] as illustrated in Sch. 15. 

The intramolecular aziridination of 2-(alkenyl)phenyl azides was best performed under pho-tolytic conditions116-117, generating the nitrene (ca. 0.001 M solution in cyclohexane, 350 nra, Rayonet Photoreactor)118. The nitrene addition reaction proceeded with complete diastereose-lectivity, the double bond geometry was retained in the aziridine thus produced. The alkaloid ( )-virantmycin was synthesized from the aziridine 2117. 

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. 

Like carbenes, nitrenes also insert into C-H bonds and add to double bonds. In some of the most useful nitrene addition reactions, however, free nitrenes are not involved rather a carrier such as a transition-metal complex or an iodine or bromine reagent is... 

Nitrene addition reactions have somewhat more scope when the reactions are carried out by azide photolysis for example, the acyinitrene pivaloylnitrene adds in moderate yield and with good stereoselectivity to cj>alkenes when it is generated from pivaloyl azide by photolysis in dichloromethane." Similarly p-cyanobenzoylnitrene, when generated by photolysis of the azide 21 in the presence of 2,5-dihydrofuian, gives the aziridine 22 in moderate yield (Scheme 6.11)." This nitrene and other p-substituted benzoylnitrenes also react with Cgo to give fulleroaziridines such as 23." ... 

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." " ... 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Fig. 6. Coupling of polymer chains via (a) photoinduced hydrogen abstraction free-radical reactions and (b) nitrene insertion/addition reactions.

Intermediate arylamidine, 6S, is prepared by the aluminum chloride-catalyzed addition of aniline to the nitrile function of 4-cyanothiazole (67), Amidine, 65, is then converted to its N-chloro analog (69) by means of sodium hypochlorite. On base treatment, this apparently undergoes a nitrene insertion reaction to produce thiabendazole (70), ... 

Intramolecular insertion and addition reactions are very rare for alkyl nitrenes. In fact, it is not clear that the nitrenes are formed as discrete species. The migration may be concerted with elimination, as is often the case in the Wolff rearrangement.251... 

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. 

Cycloadditions to [6,6]-double bonds of Cjq are among the most important reactions in fullerene chemistry. For a second attack to a [6,6]-bond of a C q monoadduct nine different sites are available (Figure 10.1). For bisadducts with different but symmetrical addends nine regioisomeric bisadducts are, in principle, possible. If only one type of symmetrical addends is allowed, eight different regioisomers can be considered, since attack to both e - and e"-positions leads to the same product. Two successive cycloadditions mostly represent the fundamental case and form the basis for the regioselectivity of multiple additions. In a comprehensive study of bisadduct formations with two identical as well as with two different addends, nucleophilic cyclopropanations, Bamford-Stevens reactions with dimethoxybenzo-phenone-tosylhydrazone and nitrene additions have been analyzed in detail (Scheme 10.1) [3, 9, 10]. 

Catalytic methods are suitable for nitrene transfer," and many of those found to be effective for carbene transfer are also effective for these reactions. However, 5- to 10-times more catalyst is commonly required to take these reactions to completion, and catalysts that are sluggish in metal carbene reactions are unreactive in nitrene transfer reactions. An exception is the copper(ll) complex of a 1,4,7-triaza-cyclononane for which aziridination of styrene occurred in high yield, even with 0.5 mol% of catalyst. Both addition and insertion reactions have been developed. 

Representative examples of ring syntheses involving carbenoid (Table 6) or nitrenoid (Table 7) intermediates are given. In many cases, the free carbene or nitrene is probably not involved, and the distinction between insertion and addition reactions given in the tables is not always clear cut. Such reactions are particularly useful for the preparation of tricyclic compounds. 

The addition reactions of organic azides to unsaturated systems can occur by two mechanisms.1 If the reaction temperature is lower than the decomposition temperature of the azide, a 1,3-dipolar addition is observed. When, however, the reaction is carried out at the wavelength or at the decomposition temperature of the azide, the addition proceeds through an intermediate nitrene. 

In contrast, nitrene addition under the same conditions (80JCS(P2)385) is non-selective, affording the diastereomeric sulfimides in 1 1 mixture (equation 13). Again the dominant factors may be steric as reaction of the same nitrenes with mixed acyclic sulfides shows little selectivity. Sulfimines are also formed by the action of N- chloroarenesulfonamide sodium salts on the sulfide, and an extensive kinetic investigation (76T2763) has sliown the minor influence of steric factors in this reaction as well. Equation (14) sets out the proposed course of the reaction. 

The most popular type of photosensitive functionality is the aryl azide derivative. On photolysis, phenyl azide groups form short-lived nitrenes that react rapidly with the surrounding chemical environment (Gilchrist and Rees, 1969). Nitrenes can insert nonspecifically into chemical bonds of target molecules, including undergoing addition reactions with double bonds and insertion reactions into active hydrogen bonds at l"l C—H and N—H sites. Abundant evidence, however, indicates that the photolyzed... 

A number of other groups have investigated the clustering reactions of small cation silicon species with silanes and other small molecules. The ion-molecule reactions occurring between SiHv+ (x = 0-3) cations and neutral ammonia, as well as the reactions between NHt+ cations and SiH4 were studied by FIMS113,114. The main channel for the reaction between SiHv+ ions and NH3 was found to correspond to the elimination-addition reaction, well-known for silanes (equation 20), which formally corresponds to the transfer of a nitrene-unit (NH)113. 

Addition chemistry has developed into a promising tool for the modification and derivatization of the surface of nanotubes [24, 26], However, it is difficult to achieve chemoselectivity and regioselectivity control of addition reactions, requiring hot addends such as arynes, carbenes, radicals, nitrenes or halogens under drastic reaction conditions. 

The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

In addition to rhodium and ruthenium, silver catalysts have also been investigated, and this chapter discusses these silver-based nitrene transfer reactions.2 1 In discussing the work chronologically, we hope that the readers can get an idea of the evolution of thinking in the research process. 

In general, nitrenes can be exploited in the amination of target molecules by insertion and addition reactions. The properties of nitrenes strongly depend on the substituent that is connected to the N-atom the most reactive... 

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