Amides from nitrenes

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... 

Iminoboianes have been suggested as intermediates in the formation of compounds derived from the pyrolysis of azidoboranes (77). The intermediate is presumed to be a boryl-substituted nitrene, RR BN, which then rearranges to the amino iminoborane, neither of which has been isolated (78). Another approach to the synthesis of amino iminoboranes involves the dehydrohalogenation of mono- and bis(amino)halobotanes as shown in equation 21. Bulky alkah-metal amides, MNR, have been utilized successfully as the strong base,, in such a reaction scheme. Use of hthium-/i /f-butyl(ttimethylsilyl)amide yields an amine, DH, which is relatively volatile (76,79). 

From N-oxides of aromatic bases oxaziridines were obtained only at very low temperatures, but oxaziridines were often postulated as intermediates in the photoconversion of such N-oxides (Section 5.08.3.1.2). Isolation of the more stable photoisomers of nitrones also causes some problems due to their thermal and photochemical instability leading to acid amides, e.g. (69TL2281), or, by fragmentation, to carbonyl compounds and products of stabilization of nitrenes, e.g. from (260) (69ZN(B)477). 

Another conceptually unique approach in alkene aziridination has come from Johnston s labs. These workers shrewdly identified organic azides as nitrene equivalents when these compounds are in the amide anion/diazonium resonance form. Thus, when a range of azides were treated with triflic acid and methyl vinyl ketone at 0 °C, the corresponding aziridines were obtained, in synthetically useful yields. In the absence of the Bronsted acid catalyst, cycloaddition is observed, producing triazolines. The method may also be adapted, through the use of unsaturated imi-des as substrates, to give anti-aminooxazolidinones (Scheme 4.25) [32]. 

On the other hand, thermolysis of ferrocenylsulpkonyl azide (14) in aliphatic solvents may lead to the predominant formation of the amide (16) 17>. A 48.4% yield of (16) was obtained from the thermolysis in cyclohexane while an 85.45% yield of 16 was formed in cyclohexene. Photolysis of 14 in these solvents led to lower yields of sulphonamide 32.2% in cyclohexane, 28.2% in cyclohexene. This suggests again that a metal-nitrene complex is an intermediate in the thermolysis of 14 since hydrogen-abstraction appears to be an important made of reaction for such sulphonyl nitrene-metal complexes. Thus, benzenesulphonamide was the main product (37%) in the copper-catalyzed decomposition of the azide in cyclohexane, and the yield was not decreased (in fact, it increased to 49%) in the presence of hydroquinone 34>. On the other hand, no toluene-sulphonamide was reported from the reaction of dichloramine-T and zinc in cyclohexane. 

The photochemical reaction can also proceed via the triplet state and in this case no cyclization is observed. Especially when acetophenone is added as a triplet sensitizer, 41 is not formed. Remarkable is the observation that in the presence of anthracene or pyrene as triplet quencher, the yield of the cyclization product 41 was not enhanced and that nitrene insertion into CH bonds of anthracene or pyrene was observed. When the photochemical cyclization reaction was performed with the tosyl azide derivative 42a or the azido nitrile derivative 42b (Scheme 6), only low yields of the tricyclic amide 41 (32% from 42a, 9% from 42b, respectively) were obtained <2001JCS(PI)2476>. 

When compared to aziridination or sulfoxide imination, efficient amidation of C-H bonds is a more formidable task since it involves the activation of relatively inert C-H bonds. With an increase in the difficulty of the reaction comes an increase in the value of products, as many are derived from cheap simple hydrocarbons. In addition to making more valuable materials in fewer steps, a better mechanistic understanding of nitrene transfer can also be gleaned, leading to the development of efficient catalysts. 

Metal nitrene complexes were used in a number of C-H amination reactions (recent reviews [358, 359]). Copper ketiminate complexes react with azides to nitrene complexes, which were isolated [360]. (p-Ketiminate)copper(I) complex 262 (2.5 mol%) serves therefore as an efficient catalyst for the intermolecular C-H amination of alkylarenes, cycloalkanes, or benzaldehydes 260 using adamantyl azide 261 as the nitrogen source ig. 68) [361]. The corresponding adamantyl amines or amides 263 were isolated in 80-93% yield. Copper complex 262 forms initially a dinuclear bridged complex with 261. From this a copper nitrene complex is generated by elimination of nitrogen, which mediates the hydrogen abstraction from 260. 

The nitrogen source for the aziridination of alkenes, a nitrene or nitrenoid, can be generated in various ways (1) oxidation of a primary amine (2) base-induced -elimination of HX from an amine or amide with an electronegative atom X (X = halogen, O) attached to the NH group or by -elimination of metal halides from metal A-arenesulfonyl-A-haloamides (3) metal-catalyzed reaction of [A-(alkane/arenesulfonyl)imino]aryliodanes (4) thermolytic or photolytic decomposition of organyl azides and (5) thermally induced cycloreversion reactions . 

If this mechanism is really operative, the "abstraction product" formed in benzene is not necessarily due to a triplet nitrene precursor. Recently a careful study of the thermolysis of methylazide in substituted benzenes demonstrated that the unsubstituted primary sulfonamide is a product of hydrogen abstraction by the nitrene 72). On the other hand there are remarkable differences in isomer ratios (o m p) of the ring-substituted anilides formed depending on the spin state of the reacting nitrene. The triplet was shown to attach the aromatic nucleus mainly in the o-position, as is expected from a highly electrophilic diradical. Dehydrogenations by carbonylnitrenes have been reported by several authors for a variety of systems. In the direct photolysis of ethylazidoformate 29 in cyclohexene, the amide 30 and the bicyclohexenyl 31 were isolated 35b Both products result from an abstraction reaction. 

A remarkably efficient FeCl2-catalyzed intermolecular amination of simple benzylic substrates has been described (Fig. 15) [76]. These same authors have also noted the ability of CuBr to operate in a similar capacity [77]. iV-Bromosucci-mide (NBS) is used as the oxidant together with either a carboxamide or sulfonamide starting material. The /V-brominated amide purportedly reacts with FeCF to generate an Fe nitrene species that is capable of oxidizing benzylic C-H bonds, though evidence for such a mechanism is absent from the discussion. If a nitrenoid pathway is indeed operative, one might expect isocyanate formation to compete... 

The dediazoniation of the vinyl azide proceeds via vinyl nitrene. A variant of this synthesis enables the preparation of 3-(dialkylamino)-2//-azirines starting from A,7V-disubstituted acid amides [15] ... 

A new method for preparing triphenylarsinimines Ph3As==NX, where X = Ph, CN, Bz, C02Et etc., from triphenylarsine and azides (XN3) under nitrene-producing conditions has been reported. The compounds also result when triphenylarsine reacts with amides in the presence of lead tetraacetate, probably via Ph3As(OAc)2 as an intermediate. 

Several phenyliodonium imides 465 derived from heteroarenesulfonylamides have been synthesized from (diacetoxyiodo)benzene and the respective amides 464 (Scheme 2.134) [630], Imides 465 can be used as sources of the corresponding heterocycle-containing nitrenes in the copper-catalyzed aziridination and sulfimidization reactions. 

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