1- pyridine, radical cyclisation

The same group went on to show that radical cyclisations to C3 of a pyridine were also favourable at neutral pH <01TL9061, 030BC4047>. Thus, on treatment with tributyltin hydride and AIBN, azastilbene 154 underwent cyclisation to benzo[/]quinoline 155 in 47% yield (Scheme 43), while the corresponding reaction with iodide 157 gave benzo[/i]isoquinoline 159 in near quantitative yield (Scheme 44). 

Irradiation of iodopyridines generates pyridinyl radicals, which will effect radical substitution of aromatic componnds. Pyridinyl radicals can be generated from halo-pyridines, using tin hydrides, and participate in typical radical cyclisation reactions. Each of the three bromo-pyridines is converted, by tris(trimethylsilyl)silane and azobis(isobutyronitrile), into a radical which substitutes benzene. ... 

The radical reductive cyclisation of diesters to acyloins (see also Section 5.9.1, p. 628) is an important method of synthesis for ring sizes from four-membered upwards. The example selected here is 2-hydroxy-3-methylcyclopent-2-enone ( corylone ) (29) (Expt 7.10), which is an important perfumery and flavouring material.53 In the first step (i), methyl acrylate is converted into its dimer with tris(cyclohexyl)phosphine in pyridine solution.5b Step (ii) is the protection of the double bond by conversion into the dimethylamino adduct. The acyloin reaction is step (iii), and the product is trapped as its bis(trimethylsilyl)ether. Finally, in step (iv), the protecting dimethylamino and trimethylsilyl groups are removed by passage down a column of silica gel. 

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). 

Notably, when the same cyclisation was carried out using sodium cobalt(I)salophen, the reaction became selective for toddaquinoline methyl ether <00TL6681>. This apparent diehotomy was attributed to the formation of a Lewis acid - Lewis base complex between cobalt(II)salophen and the pyridine moiety. Loss of bromide from the radical anion 151 generates aryl radieal 152 which adds to the proximal pyridine giving 153. Dehydrocobaltation to toddaquinoline methyl ether 149 completes the sequence (Scheme 42). Notably, as the pyridine ring is activated by complexation to the Lewis acidic Co(II), the eyelisation is more akin to a Minisci reaction. Consequently, cyclisation to C6 is promoted in this case <01T4447>. 

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). 

Irradiation of the thiopyran derivative (292a) results in extrusion of HNCS and the formation of the pyridine (292b, 63.3%) as the major product. The photochemical reactivity of the pyranthione (293) is concentration dependent in 3-methylpentane as solvent. At low concentrations the thione reacts with the solvent but at higher concentrations the main reaction is the production of thiyl radicals. Laser flash photolysis has been used to identify that the triplet excited state of (294) is involved in addition reactions which occur to electron deficient alkenes such as acrylonitrile giving (295), for example. Other compounds related to thiourea are also photochemically reactive. Thus the photochemical cyclisation of (296) to afford (297) has been reported. ... 

The benzoyidihydroindole shown formed by the reaction of 3,4-methylenedioxybenzoyl chloride and 7-bromo-5-nitrodihydroindole in pyridine at 100°C upon reaction at 155°C in dimethyl sulphoxide containing potassium carbonate and BTAC was cyclised to the isoquinolone derivatives (B) and (C) (1 1) in 27% yield. This ring closure was considered to proceed by way of a radical intermediate, (ref. 100) and constituted a route to the alkaloid ungeremine (A) after three more steps on compound (B) consisting of the conversions, -NO2... 

As shown, 5-exo-trig cyclisation proceeds smoothly following Beckwith s conditions for the corresponding phenyl substrates (85T3925), demonstrating that pyridyl radicals undergo addition to unsaturated bonds in a similar fashion to phenyl radicals. In a very different type of reaction, Harrowven synthesised thieno(2,3-li)pyridines lla-c from ketenedithioacetals via the 2-pyridyl radical precursor 10 (95TL2861) (Scheme 3). 

Analogous to Scheme 23, Markgraft (05T9102) also described addition of a carbazole and an azacarbazole radical to a pyridine ring to produce cyclised 268 and 270 in good yield (Scheme 75). 

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