Nitrenes precursors

N-Aminobenzoxazolin-2-one (4), which was readily prepared by animation of benzoxazolin-2-one with hydroxylamine-O-sulfonic acid, is also a useful nitrene precursor (Scheme 2.2). Oxidation of 4 with lead(iv) acetate in the presence of a conjugated diene resulted in exclusive 1,2-addition of nitrene 5, to yield vinylazir-idine (6) in 71 % yield [6]. The formation of vinylaziridines through 1,2-additions of methoxycarbonylnitrene (2) or amino nitrene 5 contrasts with the claimed 1,4-ad-dition of nitrene itself to butadiene [7]. Since the reaction proceeded stereospecif-ically even at high dilution, the nitrene 5 appears to be generated in a resonance-stabilized singlet state, which is probably the ground state [8]. 

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 ). 

Since the mid-1990s, synthetic attention has been directed more towards the use of metal-stabilized nitrenes as synthetic effectors of alkene aziridination. In 1969 it was reported that Cu(i) salts were capable of mediating alkene aziridination when treated with tosyl azide, but the method was limited in scope and was not adopted as a general method for the synthesis of aziridines [12]. Metaloporphyrins [13] were shown to be catalysts for the aziridination of alkenes in the presence of the nitrene precursor N-tosyliminophenyliodinane [14] in the early 1980s, but the reaction did... 

In 1982, Breslow and coworkers reported the first example of iron-catalyzed nitrene C-H bond insertion [29]. They used [Fe(TTP)] as catalyst and PhINTs as nitrene precursor to achieve C-H bond amination of cyclohexane. However, the product yield was low (around 10%). Subsequently, the same authors found that iminoio-dane 7 derived from 2,5-diisopropylbenzenesuIfonamide underwent intramolecular C-H amination efficiently with [Fe(TPP)Cl] as catalyst at room temperature, giving the insertion product in 77% yield (Scheme 29) [85]. 

This has been mentioned at various points in this paper and may involve either a direct acid-base reaction of nitrene and nucleophile or, in some instances, reaction of the nitrene precursor with the nucleophile (or 1,3-dipolarophile) followed by loss of nitrogen. For example, the reaction of benzenesulphonyl azide with pyridine to give 31 (Ar=Ph) 69> could either involve a free nitrene or a concerted process in which the lone pair on the pyridine nitrogen atom assists the elimination of molecular nitrogen. That some free nitrene can be involved in these reactions is clear from the isolation of some 3-benzenesulphonamido-2,6-lutidine... 

The aziridines are the nitrogen analogs of the epoxides and undergo similar electrophilic reactions. No biological data were obtained for these compounds nor were they used as precursors to any CA-4, 7, analogs. They have been included since the synthesis is noteworthy, and they could be interesting intermediates. Xu et al. stereoselectively aziridinated chalcones using the nitrene precursor (PhINTS) and a copper catalyst to form compound 141 (Scheme 36) [82],... 

In recent years, the related C-H insertion chemistry of nitrenes has gained considerable momentum.36 Effective chiral catalysts have been developed as well as new methods for generation of the nitrene precursors. Even more impressive has been the application of this chemistry to the synthesis of complex natural products. The scope of this chemistry is described in Section 10.04.4. 

Nitrenes can be generated from many precursors such as azides, isocyanates, ylides, heterocycles, and nitro compounds.236,237 Amongst these, azides are the most convenient precursors since they are easily prepared and can be decomposed by heat, light or a suitable catalyst. Despite considerable endeavors, no one has yet provided a synthetically viable method to use azides as sources of nitrenes.237 The breakthrough of nitrene chemistry was the recognization of the value of A-arenesulfonyl iminoiodinanes (ArS02N=IPh) as nitrene precursors by Breslow and Mansuy. - They reported inter- and intramolecular C-H insertions by tosylimino phenyl-iodinane (TsN=IPh) in the presence of Mn(m) or Fe(m) porphyrins or [Rh2(OAc)4]. Subsequently, Muller... 

The first metal-catalyzed nitrogen atom-transfer process was reported by Kwart and Khan, who demonstrated that copper powder promoted the decomposition of benzenesulfonyl azide when heated in cyclohexene.280 Evans has demonstrated that Cu(i) and Cu(n) triflate and perchlorate salts are efficient catalysts for the aziridination of olefins employing TsN=IPh as the nitrene precursor.281 Subsequent to this finding, intensive effort has focused on the identification of... 

Porphyrin complexes, which have been mentioned in the previous section as catalysts for the epoxidation of olefins, can also catalyze aziridination120 using [A-(p-toluenesulfonyl)imino]phenyl iodinane or other nitrene precursors. 

Electron-rich as well as electron-deficient olefinds undergo aziridination by decomposition of [A/-(/ -tolylsulfonyl)imino]phenyliodinane (19) with a catalytic amount of the soluble Cu(I) and Cu(II) triflate and perchlorate salts (Eq. 8) (91JOC6744 94JA2742). Phenyliodinane 19 acts as nitrene precursor. The Cu(I) catalyzed aziridination when applied to enol silanes... 

Azides are virmally the only nitrene precursors that have been used in matrix isolation studies. They are usually easily accessible, but should only be made and handled in very small quantities because certain azides can be violently explosive. 

Copper complexes catalyze formally related aziridination of olefins with ]7V-(p-toluenesulfonyl)imino]phenyliodinane, a nitrene precursor (219b). As exemplified in Scheme 98, catalysts formed from Cu(I) tri-flate and optically active bis(oxazolines) effect enantioselective reaction of styrene (Scheme 98) (218b, 219a). 

Enantioselectivity of copper-catalyzed aziridination is dependent on the nitrene precursor used (Scheme 6B.32) [77]. Although the precursor of choice varies with the substrates, /j-Me0C6H4S02N=lPh orp-02NC6H4S02N=IPh is superior to TsN=IPh in many cases. For example, the aziridination of styrene in the presence of copper-bisoxazoline complex 29b gives the product with 78% ee using p-Me0C6H4S02N=IPh as the nitrene precursor, whereas the enantioselectivity is 52% ee when TsN=IPh is used as the precursor. 

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... 

Af-(/ -Tolylsulfonyl)imino]phenyliodinane, PhI=NTs, is a well-known nitrene precursor.69 It has now been used to imidate aldehydes (i.e. RCH=0 RCH=NTs) using a ruthenium(II) catalyst and triphenylphosphine. Ph3P=NTs formation is proposed to occur, followed by aza-Wittig reaction. 

Purified SWCNTs are dispersed in 1,1,2,2-tetrachloroethane (TCE) in an ultrasonic bath under a nitrogen atmosphere over several hours. The suspension is heated to 160 °C and a 200-fold excess of ethyl azidoformate as nitrene precursor... 

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... 

As stated in the introduction, chloramine-T (where T denotes three crystalline water molecules) is a commonly used nitrene precursor, which is commercially available and costs less than do most other nitrene sources. The benefit of a silver salt in nitrene transfer reactions with chloramine-T is surprisingly simple. Because silver chloride is insoluble in most solvents, substoichiometric amounts of silver salts (like silver nitrate) can be used to remove the chloride from chloramine to facilitate the release of a free nitrene radical, which can aziridinate olefins. Since the amount of silver is near stoichiometric, it should not be called silver-based catalysis, although turnover numbers (TONs) higher than 1 have been observed in some cases. 

More importantly, this silver system catalyzes the intermolecular amination of hydrocarbons, as shown in Table 6.3. In addition to animating weaker benzylic C-H bonds, stronger aliphatic C-H bonds such as those in cyclohexane were also reactive. Although yields with more inert hydrocarbons were modest with the bathophenan-throline system, the discovery of the first silver-catalyzed intermolecular amination opens opportunities for further developments. This reaction favored tertiary cyclic sp3 C-H bonds over secondary cyclic sp3 C-H bonds, and showed limited success with simple linear alkanes. No conversion was observed with any aromatic C-H bonds. The compound NsNH2 was tested as the nitrene precursor with different oxidants. The use of PhI(OAc)2 as oxidant gave the expected amination product with a lower yield, while persulfate and peroxides showed no reactivity. 

Zraras-aziridine products were still detected from r/.v-olefin substrates, and sometimes as the predominant product. Current results on silver-catalyzed nitrene transfer reactions, indicate that silver probably can interact with iminoiodanes to generate a silver nitrene precursor. This precursor can lead to reactions via either a concerted metal nitrene or a stepwise radical pathway, depending on the substrate and reaction conditions (Scheme 6.8). 

Among other convenient nitrene precursors are chloramine-T (A-chloro-A-sodio-p-toluenesulfonamide), bromamine-T, sulfonamides in the presence of (diacetoxyiodo)benzene and various transition metal catalysts, and sulfonyl azides in the presence of ruthenium complexes . 

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