Nitrogen electrophiles oxides

SOME COMMON NITROGEN ELECTROPHILES OXIDES, OXOACIDS, AND OXOANIONS... 

Since dioxiranes are electrophilic oxidants, heteroatom functionalities with lone pair electrons are among the most reactive substrates towards oxidation. Among such nucleophilic heteroatom-type substrates, those that contain a nitrogen, sulfur or phosphorus atom, or a C=X functionality (where X is N or S), have been most extensively employed, mainly in view of the usefulness of the resulting oxidation products. Some less studied heteroatoms include oxygen, selenium, halogen and the metal centers in organometallic compounds. These transformations are summarized in Scheme 10. We shall present the substrate classes separately, since the heteroatom oxidation is quite substrate-dependent. 

Thermal and Photochemical Reactions Electrophilic Attack at Nitrogen Electrophilic Attack at Carbon Nucleophilic Attack at Carbon Nucleophilic Attack at Hydrogen Reduction Oxidation... 

Enolate anions derived from syn and anti 2-substituted 2-acyl-13-dithiane 1-oxides react readily with the nitrogen electrophile di-t-butyl azodicarboxylate (DBAD) to give a-aminoketones with good diastereoselectivity and in moderate yields (Scheme 4.64) [121]. A low-temperature acetic acid quench is necessary and is believed to prevent loss of stereochemical integrity at the new asymmetric centre which can otherwise occur. 

Just as for disubstituted nitrogen, H2O2 itself is electrophilic enough to oxidise many sulphides without a catalyst, the product being the sulph-oxide [207]. Addition of a stoichiometric amount of 35% w/w H2O2 to the sulphide in water, alcohol [208] or acetic acid [209] solution is the usual procedure. The reaction is acid-catalysed [210] and assisted by protic solvents. The rate of this electrophilic oxidation is increased by electron-donating substituents hence, reactivity can be ranked as follows ... 

Mustard reacts with a wide variety of nucleophiles. Exemplified within this class of reactivity are reactions with hydroxide ion (hydrolysis) and reactions with sulphur and nitrogen nucleophiles. In addition, divalent sulphur is electron rich, and consequently mustard is also attacked by electrophiles. Oxidation, chlorination and complexation typify this class of reactions. Recent studies have also explored the possibility of using biomimetic systems (catalase) to achieve facile oxidation of mustard by peroxide moieties. 

The use of oximes as nucleophiles can be quite perplexing in view of the fact that nitrogen or oxygen may react. Alkylation of hydroxylamines can therefore be a very complex process which is largely dependent on the steric factors associated with the educts. Reproducible and predictable results are obtained in intramolecular reactions between oximes and electrophilic carbon atoms. Amides, halides, nitriles, and ketones have been used as electrophiles, and various heterocycles such as quinazoline N-oxide, benzodiayepines, and isoxazoles have been obtained in excellent yields under appropriate reaction conditions. 

Because Pd(II) salts, like Hgtll) salts, can effect electrophilic metallation of the indole ring at C3, it is also possible to carry out vinylation on indoles without 3-substituents. These reactions usually require the use of an equiv. of the Pd(ll) salt and also a Cu(If) or Ag(I) salt to effect reoxidation of the Pd. As in the standard Heck conditions, an EW substitution on the indole nitrogen is usually necessary. Entry 8 of Table 11.3 is an interesting example. The oxidative vinylation was achieved in 87% yield by using one equiv. of PdfOAcfj and one equiv. of chloranil as a co-oxidant. This example is also noteworthy in that the 4-broino substituent was unreactive under these conditions. Part B of Table 11.3 lists some other representative procedures. 

Thus in neutral medium the reactivity of 2-aminothiazoles derivatives toward sp C electrophilic centers usually occurs through the ring nitrogen. A notable exception is provided by the reaction between 2-amino-thiazole and a solution (acetone-water, 1 1) of ethylene oxide (183) that yields 2-(2-hydroxyethylamino)thiazole (39) (Scheme 28), Structure 39... 

With a peroxyacid, the reagent used in their preparation, oxaziridines further react to yield aliphatic nitroso compounds. An electrophilic attack to ring nitrogen is plausible, leading to an intermediate oxaziridine N-oxide (81), which immediately decomposes to a nitroso compound and an aldehyde (57JA6522). 

It was not their reactivity but their chemical inertness that was the true surprise when diazirines were discovered in 1960. Thus they are in marked contrast to the known linear diazo compounds which are characterized by the multiplicity of their reactions. For example, cycloadditions were never observed with the diazirines. Especially surprising is the inertness of diazirines towards electrophiles. Strong oxidants used in their synthesis like dichromate, bromine, chlorine or hypochlorite are without action on diazirines. Diazirine formation may even proceed by oxidative dealkylation of a diaziridine nitrogen in (186) without destruction of the diazirine ring (75ZOR2221). The diazirine ring is inert towards ozone simple diazirines are decomposed only by more than 80% sulfuric acid (B-67MI50800). 

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

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