Sp2 carbon-centered radical

Rate constants for the ring-closure by the sp2 carbon-centered radical are shown in Table 1.3. The rate constants are increased more than those of sp3 carbon-centered radicals, because the sp2 carbon-centered radical is much more reactive than sp3 carbon-centered radicals. This high reactivity of the sp2 carbon-centered radical is reflected by the stronger bond-dissociation energy of the sp2(carbon)-sp3(carbon) bond than that of the sp3(carbon)-sp3(carbon) bond. 

Rate constants for ring closure (s 1, 25 °C) (sp2 carbon-centered radicals)... 

Treatment of acyl halides (3) with Sml2 provides 1,2-diketones (4) via the coupling of acyl radicals, which are sp2 carbon-centered radicals (eq. 2.2). Generally, aromatic acid halides are more reactive than aliphatic acid halides. 

Eq. 3.44 shows the intramolecular addition of an sp2 carbon-centered radical onto the quinoline group under the same conditions. 

Eq. 3.48 shows a specific radical reaction. Thus, the formed sp2 carbon-centered radical cyclizes at the vinylic position via 5-exo-trig manner and subsequent (3-cleavage to produce an o-hydroxystilbene skeleton (137), together with evolution of S02 [147, 148]. This reaction has the appearance of a 1,4-transfer of the phenylvinyl group from the sulfur atom to an sp2 carbon atom. 

A more interesting reaction is the shift of an sp2 carbon-centered radical to an sp3 carbon-centered radical via 1,5-H shift as shown in eq. 3.53. The formed sp2 carbon-centered radical abstracts a hydrogen atom via 1,5-H shift to generate an sp3 carbon-centered radical which then cyclizes at the olefinic position via 5-exo-trig manner to produce a cyclopentane derivative (147) [157-160]. The rate constant of this 1,5-H shift is approximately 3 X 107 s 1, and is quite fast. 

Since a vinyl radical is also an sp2 carbon-centered radical, a similar 1,5-H shift from the sp2 carbon-centered radical to the sp3 carbon-centered radical occurs, as shown in eq. 3.54, which finally produces heliotridanes (149) via the... 

Spirocyclic pyrrolidin-2-ones (151) are prepared through the initial 1,5-radical translocation by an sp2 carbon-centered radical, followed by cyclization as shown in eq. 3.55 [161]. 

Cyclization to carbonyl groups by sp3 or sp2 carbon-centered radicals and other related reactions... 

The same %-endo-trig cyclization can also be carried out with sp2 carbon-centered radicals, as shown in eq. 3.84. Thus, the preparation of mms -pyrano[3,2-c][2]benzox-ocines (216) was produced in good yields through %-endo-trig manner of aryl radicals derived from D-mannose pyranosides (215), using the Bu3SnH /AIBN system. 

Ce4+ can be also used for the same type of reaction, since it is a strong one-electron oxidant. Generation of sp2 carbon-centered radicals such as aryl radicals, is not so easy, except for the reactions of aryl halides with Bu3SnH or Ph4Si2H2. However, treatment of arylhydrazines with Cu2+ generates aryl radicals through the initial oxidation to the arenediazonium ion with Cu2+, and subsequent SET from Cu+. Aryl radicals are much more reactive than alkyl radicals, and rapidly react with alkenes or imines as shown below (eq. 4.22) [60-63]. 

Reactivities of n-Bu (sp3 carbon-centered radical) and Ph (sp2 carbon-centered radical) to benzene, y-picoline, protonated y-picoline, protonated benzothiazole are shown in Table 5.1. As can be seen here, the reactivity is greatly increased in both radicals, as the electron-density of aromatics is decreased. Therefore, the reactivity of heteroatomatic bases such as y-picoline and benzothiazole, can be increased by their... 

However, the sp3 carbon-centered radical does not generally give rise to 1,5-H shift, although the sp2 carbon-centered radical can be used for 1,5-H shift, since it is more reactive than the sp3 carbon-centered radical and it can form a strong C(sp2)-H bond (10 15 kcal/mol stronger than that of C(sp3)-H). Eq. 6.22 shows the product distribution of a direct reduction product (43a) and an indirect reduction product (43b) via 1,5-H shift, in the reaction of arylbromide (42) with Bu3SnD. It suggests that more than half of the amount of reduction product is formed via 1,5-H shift [59]. 

As a synthetic use of 1,5-H shift by an sp2 carbon-centered radical, treatment of o-bromobenzyl 4-teft-butylcyclohexyl ether (44) with Bu3SnH in the presence of AIBN generates 4-teft-butylcyclohexanone (45) by means of 1,5-H shift by a phenyl radical, followed by (3-cleavage, as shown in eq. 6.23 [60]. The reaction looks like oxidation. 

When steric hindrance in substrates is increased, and when the leaving anion group in substrates is iodide, SET reaction is much induced (Cl < Br < I). This reason comes from the fact that steric hindrance retards the direct nucleophilic reduction of substrates by a hydride species, and the a energy level of C-I bond in substrates is lower than that of C-Br or C-Cl bond. Therefore, metal hydride reduction of alkyl chlorides, bromides, and tosylates generally proceeds mainly via a polar pathway, i.e. SN2. Since LUMO energy level in aromatic halides is lower than that of aliphatic halides, SET reaction in aromatic halides is induced not only in aromatic iodides but also in aromatic bromides. Eq. 9.2 shows reductive cyclization of o-bromophenyl allyl ether (4) via an sp2 carbon-centered radical with LiAlH4. 

As a further stereoselective organic synthesis [40-47] using reactive sp2 carbon-centered radicals, eq. 10.23 shows the preparation of chiral 4-te/7-butylcyclohexene (49) from the optically pure o-bromophenyl sulfoxide (48) through 1,5-H shift by sp2 carbon-centered radical, followed by (3-elimination. This reaction looks like a thermal concerted intramolecular elimination reaction (Ei). 

Since the amide group and the aromatic ring are perpendicular (atropisomer) in N-methyl-Af-(2-iodo-4,6-dimethyl)phenyl acrylamide, free rotation between the C-N bond does not occur, so each enantiomer can be separated. Once an sp2 carbon-centered radical... 

The following are examples of other generation methods of the same kind of reactive sp2 carbon-centered radicals. Treatment of aromatic diazocarboxylate ester (11) at pH 7.2 forms the phenyl radical, through hydrolysis of the ester, decarboxylation to the phenyldiimide, and finally, reaction with molecular oxygen (eq. 11.9a). Electron transfer reduction of 1,4-diazonium (12) with Cu+ generates the corresponding /7-phenylene biradical (probably step-by-step formation) (eq. 11.9b). These simple sp2 carbon-centered radicals also destroy DNA plasmid at pH 7.6, under living-body conditions, like esperamicin [37-39]. 

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