Iminyl radicals Generation

When oxime benzoates, prepared by benzoylation of dialkyl 1-hydroxyiminophosphonates in the presence of Py, are submitted to the action of tin hydrides under radical conditions, the weakness of the N-0 bond is responsible for the fast formation of the reactive iminyl radical. In the example displayed in Scheme 7.71, the intermediate iminyl radical undergoes cyclization faster than the P-scission to nitrile to give a cyclic aminophosphonale. "- The reaction has also been explored with dialkyl l-benzoyloxyimino-2,2-dimethyl-3,4-pentadienylphosphonate and BujSnH/AIBN in refluxing cyclohexane. In this case, the iminyl radical generated by stannyl radical addition on the benzoyl moiety leads to the sole formation of phosphonylated dihydropyridine in quantitative yield. ... 

Iminyl radicals, generated by microwave irradiation of ( -phenyl oxime ethers such as 224, cychzed onto the indole 2-position to afford indolopyridine derivatives (225) [117]. The most likely pathway involves a 6-endo cyclization and was further exploited into a formal synthesis of neocryptolepine from gramine in five steps. 

Intramolecular cyclization of the iminyl radical generated from the 2,3-unsatu-rated a-C-gJycoside 85 gave the bicycle 86, that readily aromatized to the pyrrole 87 (Scheme 15). ... 

A simple route to furo[3,2-6]pyridine is based upon the one-step generation of the pyridine ring by gas-phase cyclization of conjugated iminyl radicals <80JCS(Pi)2200). O-Alkyloximes have proved to be suitable precursors (Scheme 18) (81S464). 

The photocatalytic radical generation was also used in additions to methyl cyanoformate 143 [240]. The product distribution was dependent on the reaction temperature. At room temperature ot-imino esters 144 were formed in 51-99% yield, while at 90 °C nitriles 145 were isolated in 59-76% yield. At low temperature, the iminyl radical 140C generated by the radical addition, abstracts a hydrogen atom from the substrate to continue a chain reaction, while its fragmentation to the nitrile prevails at high temperature, generating carbon dioxide and a methyl radical 146, which acts as a chain carrier. 

Recently, radical species have attracted much attention as useful intermediates for carbon-carbon bond formations. By contrast, in organic synthesis, radicals centered on heteroatoms have not been widely utilized for construction of molecular skeletons with carbon-heteroatom bond formation. In this section we will discuss the generation of alkylideneaminyl radicals, conventionally called iminyl radicals from oxime derivatives by electron transfer reactions. AU -lideneaminyl radicals thus created are utilized for making nitrogen-containing heterocycles. 

Generation of the iminyl radical 184 in the above experiment was confirmed by an intramolecular radical trapping experiment. Reaction of l-phenylhept-6-en-3-one 0-2,4-dinitrophenyloxime (87) with m-cresol and NaH afforded 2-methyl-5-(l-phenylethyl)-3,4-dihydro-2H-pyrrole (88), which is the addition product of iminyl radical 187, obtained in 27% yield (Scheme 40). 

The quinoline formation from 2,4-dinitrophenyl oximes suggested to us the possibility of generating radical intermediates and prompted us to study the synthesis of cyclic imines by iminyl radical addition to an internal olefinic moiety as shown in Scheme 44. 

N-centered radicals such as iminyl radicals can also be generated from a radical cyclization step onto nitrile groups. The fate of the iminyl radical depends on the nature of the a-substituent. When this latter is an alkyl group, further cychzation can take place [45]. A combination of both processes has been achieved addition of a staimyl radical onto an azide moiety generated a N-stannylaminyl radical that cyclized onto a nitrile and underwent further cyclization, thus opening access to pyrrolopyrroles and pyrrolopyridines derivatives [46]. 

Iminyl radicals are generated by the addition of tributylstannane to N-chloro25 or, more conveniently, A -arylthio imines26,27 , 32. These radicals display considerable reactivity towards unactivated C—C double bonds in intramolecular reactions. 3,4-Dihydro-2//-pyrroles were obtained in good yield with variable stereoselectivity by the slow addition (4-5 h) of tributylstannane to a refluxing cyclohexane solution of suitable unsaturated jV-(2-benzo-thiazolylthio) and Ar-phenylthio imines (Table 2). 

A further example of a one-bond-forming pyridine synthesis is provided by the intramolecular cyclization of 0-alkyl-oximes such as (3) under conditions of flash vacuum pyrolysis. Cyclization occurs as a result of the generation of conjugated iminyl radicals (4) (Scheme 1). ... 

Furthermore, iminyl radicals, which are supposed to be intermediates in the annulations discussed above (see 32), have been directly generated from the corresponding oximes [56] or hydrazones [57] and applied in the intramolecular homolytic aromatic substitution. The intramolecular radical alkylation of arenes [58] and heteroarenes [59-62] was investigated by various research groups. As for the aryl radicals, the alkyl radicals used in these reactions are generally generated from the... 

Iminyl radicals are particularly useful for the construction of nitrogen heterocycles, since the cyclization products are functionally disposed for further elaboration into a variety of useful systems. Zard and coworkers have pioneered the development of methodology for the generation and cyclization of iminyl radicals (Table 8) [5, 71]. Iminyl radicals cyclize one order of magnitude more rapidly than the related neutral aminyl radicals but react less rapidly than the aminyl radicals with hydrogen atom transfer trapping agents, and one would predict that iminyl radicals formed in chain reaction sequences could prove to be as versatile as carbon radicals [78]. 

Nitriles. The oximation of nitroalkanes gives nitrolic acids, and further O-acylation and treatment with BUjSnH completes the transformation to nitriles. Iminyl radicals are generated from A-benzotriazolylimines, and the fate of such radicals is either cyclization or... 

Furthermore, iminyl radicals have been used in intramolecular homolytic aromatic substitutions. The iminyl radicals can be generated in situ by C-radical addition onto nitriles [55] or they may be generated directly from the corresponding oximes [56] and hydrazones [57]. 

Leardini and Spagnolo have investigated the generation of iminyl radicals from azides via hydrogen atom transfer in the presence of tin hydride. Depending on the nature of the iminyl radicals, homolytic aromatic substitution was observed as well as conversion to the corresponding nitrile (Scheme 8.50, top). j8-Fragmentation of carbamoyl radicals has been observed as major reaction pathway with a-azidoamides (Scheme 8.50, bottom). 

Kaim LE, Meyer C (1996) An unprecedented radical reaction of benzotriazole derivatives. A new efficient method for the generation of iminyl radicals. J Org Chem 61(5) 1556-1557... 

According to the classical definition. Barton esters are mixed anhydrides of carboxylic acids with thio-hydroxamic acid such as I (Scheme Ij. This class of compound was originally developed to allow the transformation of carboxylic acids to a convenient source of radicals for synthetic application. Even now, they are one of the most important entries to C-radicals. Over time, the scope of the reaction was broadened, allowing the generation of heteroatom-centered radicals, particularly oxyl-, aminyl-, and iminyl radicals of synthetic interest. For these transformations, carbonates and carbamates (II), acetates (IV), and ethers (V) were developed (Scheme 1). Finally, oxalates (III) were used for deoxygenation of secondary and tertiary alcohols. The radical fragmentation reaction of these compounds can be carried out either by irradiation or by thermal activation. Both methods are discussed here briefly. 

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