Radicals imidoyl radical

Trialkylsilyl radicals add to alkyl isocyanate to form imidoyl radicals 56 (Reaction 5.38). Detailed EPR studies established intermediates 56 to be strongly bent at the carbon bearing the unpaired electron [76], The absolute rate constant for the reaction of Et3Si radical with ieri-butyl isocyanate was found to be 5.5 x 10 s at 27 °C [13], whereas the relative rate of the addition of MesSi radicals to alkyl isocyanates was found to decrease in the... 

Bowman et al. reported the total synthesis of ellipticine (228) involving an imidoyl radical cascade reaction (730). For this key step, the required imidoyl radical was generated from the imidoyl selanide 1290, which was obtained from ethyl 2-(4-pyridyl)acetate (1286). Reaction of 1286 with LDA, followed by addition of methyl iodide, led to the corresponding methyl derivative 1287. Treatment of 1287 with 2-iodoaniline (743) in the presence of trimethylaluminum (AlMes) afforded the amide 1288. Using Sonogashira conditions, propyne is coupled with the amide 1288 to afford the aryl acetylene 1289. The aryl acetylene 1289 was transformed to the... 

Imidoyl radicals are often prepared by the addition of carbon- or heteroatom-centred radicals to isocyanides, but can also be prepared by hydrogen atom abstraction from imines. This latter method has been adopted in a new annulation approach to quinoline synthesis. Thus, reaction of the imine 1 with phenylacetylene and di-isopropyl peroxydicarbonate in benzene at 60°C gave a mixture of the quinolines 2 and 3 in 65% yield (2 3 = 4.4). 

Scheme 6.6 illustrates a coupling reaction related to the third example of Scheme 6.4, but with diphenyl disulfide and m-dinitrobenzene [12]. The resulting imidoyl radical is trapped by m-dinitrobenzene to give the corresponding amide,... 

The addition of sulfur radicals to isocyanides produces imidoyl radicals as intermediates. The stereocontrolled 5-exo-trig cyclization of imidoyl radicals in the synthesis of substituted (alkylthio)pyrrolines, pyroglutamates, and thiopyroglutamates has been reported [95JOC6242], The intermediate 137 is not isolated but undergoes further thermal reaction to furnish a pyroglutamate derivative. 

Preparation of fluorinated organic compounds is important. Uneyama and co-workers have investigated the generation and reactions of trifluroacetimidoyl radicals [95BCSJ1497], The imidoyl radicals can be generated under three different conditions and it undergoes clean 5-exo cyclizations to provide 3-substituted indoles in moderate yields. 

Cyclization of selenoimidates.a Reaction of the selenoimidate 1 with Bu3SnH (AIBN) generates an imidoyl radical that cyclizes to the nitrile 2 and the imine 3 of a chromanone. Only 3 is obtained if the benzyl substituent on nitrogen is changed to an alkyl group. The reaction follows a different course when an N-tolyl selenoimidate (4) is the starting imine (equation I). 

Readily available thiocarbamates, thioamides, and thioureas provide direct routes to quinolines in moderate to good yields <03OL1765>. The reactive intermediate postulated is the synthetic equivalent of an imidoyl radical, but with greater utility. 

Note that aldehydes can also be a source of acyl radicals ( 0=0) via reaction with transition metal salts such as Mn(III) acetate or Fe(II) compounds.Another useful variation employs imidoyl radicals as synthons for unstable aryl radicals. 

The mechanism of the Wohl-Ziegler bromination involves bromine radicals (and not imidoyl radicals). The radical initiator is homolytically cleaved upon irradiation with heat or light, and it reacts with Bra (which is always present in small quantities in NBS) to generate the Br- radical, which abstracts a hydrogen atom from the allylic (or benzylic) position. The key to the success of the reaction is to maintain a low concentration of Bra so that the addition across the C=C double bond is avoided. The Bra is regenerated by the ionic reaction of NBS with the HBr by-product. 

A different approach to the cyclisation of biphei l derivatives involves the generation of imidoyl radicals from Schiff bases (40) using diisopropyl peroa -dicarbonate. The intramolecular homolytic substitution is apparently not regiospecific since the methozy derivative (40 R=0Me) affords a mixture of isomers (R. Leardini. A. Tundo and 6. Zanardi, Synthesis, 1985. 107). 

Radical AdditionIFragmentation Reactions the Fate of Imidoyl Radicals... 

Physical properties indicate that the dipolar contribution (1) is the major one and this structure actually accounts for the nucleophilic behavior of the terminal carbon of isonitriles. However, in terms of radical chemistry, the more interesting form is the divalent one (2). This clearly shows that the isonitrile group does not behave toward radical species like a vicinal radical acceptor/radical donor synthon, that is, like an usual unsaturated bond. It instead reacts like a geminal acceptor/donor synthon [2], where an incoming radical attacks the same carbon atom that will be the new radical center in the resulting imidoyl intermediate 3 (Scheme 1). Actually, isonitriles can serve as very efficient radical traps and this chapter reviews the structural, mechanistic, and synthetic studies carried out in this field, with outstanding results, in the last three decades. 

The first study on the structure of imidoyl radicals dates back to 1973 [11], when Danen described the ESR spectra of the radicals obtained by irradiation of cyclopropane solutions of some aldimines and di-/er -butyl peroxide. On the basis of the low g-values (2.0016) and the jff-hydrogen hyperfine splittings, the authors claimed that imidoyls are cr-radicals with a non-linear arrangement about the N=C-C bond. The facile abstraction of the aldiminic hydrogen, and hence the remarkable stabilization of imidoyl radicals, was explained by the intervention of the mesomeric forms 3a and 3b (Scheme 5), in which the unpaired electron is stabilized by interaction with the lone pair on nitrogen. 

The low values exhibited by imidoyls (1.20-1.85 G) could be accounted for through a spin polarization mechanism that induces negative spin density at the nitrogen, somewhat balancing the positive spin density resulting from resonance effect. In subsequent papers [5d,f], Roberts used isonitriles as the source of various a-heteroatom-substituted imidoyl radicals and calculated some rate constants for both the radical addition steps and the -fragmentation processes (Scheme 4, routes... 

Imidoyl radicals are in principle very attractive intermediates for the synthesis of A-heterocycles. Actually, during the great upsurge of synthetic work carried out... 

Fragmentation of imidoyl radical 34 to isothiocyanate was sometimes a competing process, especially when R H and the scission yields a fairly stable radical e.g., R = CH2C02Me) in those cases, control over the two competing reactions was gained by adequate temperature adjustment. 

It is worth noting that the same kind of reactions can be carried out by tin-radical-mediated ring closure of analogous isothiocyanates e.g., 33, 37, 39, NC = NCS) [22b,c], In this case, the intermediate a-thio-substituted imidoyl radical is generated by addition of a stannyl radical to the sulfur atom of the isothiocyanate. Although it had been known for a few decades, this way to imidoyl radicals had found very little application in organic synthesis. Bachi s work was the first example of synthesis of heterocyclic compounds by radical addition to isothiocyanates, showing the way to further possible applications [9]. 

Finally, a novel three-component radical cascade reaction involving isonitriles has just been published [6]. In this paper, aromatic disulfides, alkynes, and isonitriles have been reported to react under photolytic conditions to afford -arylthio-substituted acrylamides 49 or acrylonitriles 50 in fair yields as mixtures of the E and Z geometric isomers (Scheme 21). The procedure entails addition of a sulfanyl radical to the alkyne followed by attack of the resulting vinyl radical on the isonitrile. A fast reaction, for example, scavenging by a nitro-derivative (route a) or f-fragmentation (route b), is necessary in order to trap the final imidoyl radical, since addition of vinyl radicals to isonitriles seems to be a reversible process. The reaction provides very easy access to potentially useful poly-functionalized alkenes through a very selective tandem addition sequence. 

The stereochemistry of the tandem reaction is of significance. The lower or even inverted preference for either geometrical isomer observed in this case with respect to that encountered in related hydrogen abstraction reactions by the same vinyl radicals was explained in terms of transition state interactions in the addition step to the isonitrile and/or isomerization of the final imidoyl radical. The latter possi-... 

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