Aryl radical intermediate

Sml2-mediated radical cyclisations involving alkyl, alkenyl and aryl radical intermediates can be used to construct efficiently five-membered and, in certain cases, six-membered ring systems. This approach provides a useful alternative to trialkyltin hydride-mediated methods as toxic reagents and problematic tin byproducts are avoided. In addition, the use of Sml2 to induce radical cyclisations has led to the development of a number of powerful, radical/anionic sequential processes for the construction of complex systems. Sequential reactions involving radical-alkene/alkyne cyclisations are discussed in Chapter 6. 

This is the generally accepted scheme but, according to a recent reexamination of various experimental results a reconsideration of the mechanism is possible. In certain cases at least, a nucleophilic substitution on the intermediate radical anion has also to be considered [100] and with another chain mechanism made of steps (11) and (12), the aryl radical intermediate no longer needs to be involved ... 

The diazonium salt 453, derived from aminoisoquinoline 452, undergoes thermal cyclization to afford 6-thiaellip-ticine 454 and 37/-pyrazolo[3,4-, ]isoquinoline 455. Formation of 454 may involve the cyclization of an aryl radical intermediate (Scheme 74) <1996CC2711>. Isomerically pure 4,6-dimethyldibenzothiophene 457 <1996T3953> and benzothiophene 459 <2005T8711> can be synthesized from the diazonium salts 456 and 458, respectively. 

The addition of an aryl radical intermediate to a pyridine featured as a key step in a total synthesis of the alkaloid toddaquinoline by Harrowven and Nunn <98TL5875, 00TL6681, 01T4447>. Thus, cyclisation of azastilbene 148 using tributyltin hydride and AIBN, led to both the desired product, toddaquinoline methyl ether 149, and an unwanted regioisomer 150 (Scheme 41). 

A study of the cyclisation of aryl radical intermediates to quinolines uncovered some striking differences in the reactivity profile of quinolines and pyridines towards radical intermediates <01TL2907, 02T3387>. Most notably, cyclisations involving quinolines were generally more efficient when the heterocycle and radical precursor were conjoined using a saturated tether. Moreover, in each case products derived from orf/io-cyclisation were observed irrespective of the nature of the tethering chain or its point of attachment to the quinoline (Schemes 53 - 55). 

The thermal decomposition of an (orf o-allyloxyphenyl)ketomethyllead diacetate did not afford the cyclized products resulting from aryl radical intermediates. 144... 

Diazonium salts such as (248) undergo both photochemical and thermal cyclization to afford the thiophene (249) and derivatives in 80-90% yields (Equation (42)). The reaction may involve the cyclization of aryl radical intermediates <92IZV582>. 

There are many other reactions that possibly involve aryne intermediates. While some are of mechanistic curiosities, some have been studied in detail, although none are generally synthetically useful. Irradiation of 1,2-diiodobenzene can lead to ortho-benzyne, probably via an aryl radical intermediate resulting from cleavage of the weak C-1 bond (Scheme 7.19). Aryl cations, formed by the decomposition of diazonium salts are also possible intermediates to ortho-benzynes provided that a large ortho-substituent is present, loss of a proton to give an aryne becomes competitive with the normal nudeophihc addition to the cation. 

Aryl radical intermediates were also snccessfnlly nsed for the preparation of the strained polyarene cavicularin (60) from aryl iodide 58 (Eq. 9.13). In this transformation, the key step involved the generation of the a-complex 59 with a sp carbon that was able to alleviate the strain of the macrocycle and the cyclization proceeded withont any significant distortion of arene A. The thermodynamic cost of bending the arene A was compensated by the rearomatization of arene D from the intermediate 59 [48] ... 

The aryl radical intermediate in reaction can be trapped by an aromatic ring. For example, the reaction of 131 with naphthalene-2-thiolate ions 137 afforded the ring closure product 141 (62% yield) [92]. In this case, by ET to 131 and after C—I bond fragmentation, the... 

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