Oxidative addition nitrogen nucleophiles

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. 

In addition to their reactions with amines, Zincke salts also combine with other nitrogen nucleophiles, providing various A -substituted pyridine derivatives. Pyridine A -oxides result from the reaction with hydroxylamine, as exemplified for the conversion of Zincke salt 38 to the A -oxide 39 Reactions of Zincke salts with hydrazine, meanwhile, lead... 

Hassner and coworkers have developed a one-pot tandem consecutive 1,4-addition intramolecular cycloaddition strategy for the construction of five- and six-membered heterocycles and carbocycles. Because nitroalkenes are good Michael acceptors for carbon, sulfur, oxygen, and nitrogen nucleophiles (see Section 4.1 on the Michael reaction), subsequent intramolecular silyl nitronate cycloaddition (ISOC) or intramolecular nitrile oxide cycloaddition (INOC) provides one-pot synthesis of fused isoxazolines (Scheme 8.26). The ISOC route is generally better than INOC route regarding stereoselectivity and generality. 

The use of a nitrogen nucleophile in the side chain (as an amide) also leads to an intramolecular 1,4-addition under the standard conditions for the palladium-catalyzed 1,4-oxidation reactions52. Nitrogen nucleophiles employed for this reaction comprise tosy-lamides, carboxamides, carbamates and ureas. The reactions are run in acetone-acetic acid with p-benzoquinone (BQ) as the oxidant. In most cases highly stereo- and regioselective reactions were obtained and some examples are given in Table 3. 

Pyridine is a jt-electron-deficient heterocycle. Due to the electronegativity of the nitrogen atom, the a and y positions bear a partial positive charge, making the C(2), C(4), and C(6) positions prone to nucleophilic attacks. A similar trend occurs in the context of palladium chemistry. The a and y positions of halopyridines are more susceptible to the oxidative addition to Pd(0) relative to simple carbocyclic aryl halides. Even a- and y-chloropyridines are viable electrophilic substrates for Pd-catalyzed reactions under standard conditions. 

Where there is at least one hydrogen atom on the second nitrogen, electrochemical oxidation of aroylhydrazines leads to the corresponding di-imide [147, 151]. Di-imides undergo rapid addition of a nucleophile onto the carbonyl group, cata-... 

Compared with the variety of existing carbon or nitrogen nucleophiles that were subjected to nucleophilic addition to there are few examples for phosphorus nucleophiles. Neutral trialkylphosphines turn out to be to less reactive for an effective addihon to Cjq even at elevated temperatures [114], Trialkylphosphine oxides show an increased reactivity. They form stable fullerene-substituted phosphine oxides [115] it is not yet clear if the reaction proceeds via a nucleophilic mechanism or a cycloaddition mechanism. Phosphine oxide addition takes place in refluxing toluene [115], At room temperature the charge-transfer complexes of with phosphine oxides such as tri-n-octylphosphine oxide or tri-n-butylphosphine oxide are verifiable and stable in soluhon [116],... 

Tetrakis(triethylphosphine)platinum(0) is extremely air sensitive and readily soluble in saturated aliphatic hydrocarbons. The complex can be stored under dry nitrogen in a freezer (-35°) for several months. The complex readily loses one of the coordinated phosphine molecules to give Pt(PEt3)36 (dissociation constant (K ) in heptane is 3.0 X 10" ). The H NMR spectrum measured in benzene-d6 shows two multiplets at 5 1.56 (CH2) and 1.07 ppm (CH3). Tetrakis-(triethylphosphine)platinum(O) is a strong nucleophile and reacts readily with chlorobenzene and benzonitrile to give a-phenyl complexes PtX(Ph)(PEt3)2 (X = Cl, CN).7 Oxidative addition of EtOH affords [PtH(PEt3)3] +. 

As Schaffer has found 2.4.6-triphenyl-X -phosphorin 22 and other 2.4.6-tri-substituted X -phosphorins react smoothly with aryl diazonium salts in benzene. Nitrogen develops and the aryl residue bonds with the phosphorus. In presence of alcohols as nucleophiles, l-alkoxy-l-aryl-2.4.6-triphenyl-X -phosphorins 100 can be isolated. The aryl diazonium-tetrafluoroborate without any nucleophile in DMOE yields l-aiyl-l-fluoro-2.4.6-triphenyl-X -phosphorin 70i. As with other oxidants like halogen or mercury-Il-acetate, we suppose that in the first step triphenyl-X -phosphorin radical cation is formed. This could be shown by ESR spectroscopy. The next step may be a radical-radical addition to the X -phosphorin cation or a nucleophileradical addition respectively ... 

The palladium catalysed substitution reaction of allylic systems has also been utilised in the formation of five membered rings. Intramolecular nucleophilic attack of the amide nitrogen atom on the allylpalladium complex formed in the oxidative addition of the allyl acetate moiety on the catalyst led to the formation of the five membered ring (3.63.). In the presence of a copper(II) salt the intermediate pyrroline derivative oxidized to pyrrole.80... 

In 1,3-benzazoIes (benzoxazoles, benzothiazoies, benzoselenazoles) the heteroatom that is not nitrogen shows very low nucleophilicity and does not serve as a reaction center in electrophilic addition and oxidation-addition reactions. By contrast the tellurium atom in benzotellurazoles is quite susceptible to attack by electrophiles and oxidants. 

The reaction may proceed by oxidative addition of 2 equivalents of 1 at a A3P atom of 3, producing a monophosphorane intermediate in which attack at the A3P atom by the nitrogen atom y to P, followed by nucleophilic attack of Cl- at A3P nay occur (eq. 4)... 

In this chtq)ter oxidation of an activated C—bond adjacent to a sulfur atom refers to any process whereby a C—bond at the a-position of an alkyl sulfide is replaced by a C—bond, where X is a halogen atom or an oxygen-, nitrogen-, carbon-, or sulfur-based substituent (equation 1). Processes in which a stabilized anion is generated adjacent to the sulfur atom of a sulfide, foxide or sulfone and subsequently used as a nucleophile in addition or substitution reactions are excluded ftom this section. The use of such anions in organic synthesis is dealt with in Volume 1, ClhtqMer 23. 

All the examples of the catalytic one-pot selenenylation-deselenenylation reactions reported above concern the use of oxygen nucleophiles. Also reported in Scheme 43 is the only available example in which a nitrogen nucleophile is involved in the addition step. Under the usual conditions, the oximes 271 react with phenylselenyl sulfate to afford the nitrones 272 which react with the persulfate to give pyridine AT-oxides 273 by deselenenylation and dehydrogenation [126]. 

In general, nucleophilic addition reactions of arene oxides with nonpolarizable oxygen and nitrogen nucleophiles are very slow. Thus both NH3 and NHj nucleophiles failed to add to benzene oxides under a range of conditions. Amine nucleophiles have, however, been found to react very slowly with benzene oxide. 

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