Reactions of Radical Intermediates

Under these conditions, amine radical cation la is deprotonated to form a-amino radical Ilia, which reacts with the olefin to form radical adduct Ka. Since no external oxidant is present, the adduct radical presumably turns over Ru to Ru and is reduced to the anion. Protonation of the enolate forms the product. For intramolecular additions, dehydrogenation occurs rather than reduction to provide 5,6-dihydroindolo[2,l-a]-THIQs such as 18. 

The authors provided evidence in support of amino radical Ilia as an intermediate by performing the reaction in the absence of the olefin and observing the formation of dimer 19, formed from the radical combination of Ilia with itself. Furthermore, under an oxygen atmosphere in the absence of an alkene radical. Ilia was intercepted by molecular ojg gen to form amide 8 in 42% yield. 

The authors applied this concept to intramolecular visible-light-assisted CDC reactions of olefin-tethered anilines. Irradiation of 24 with visible light 

4 Photochemical CDC Reactions Using Porphyrins/Organic Dyes 

The benefit of using transition metal photocatalysts is often selective activation over organic molecules, which typically do not absorb light in the visible range. However, a broad range of organic dyes and porphyrins with 

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Scheme 10.17 illustrates allylation by reaction of radical intermediates with allyl stannanes. The first entry uses a carbohydrate-derived xanthate as the radical source. The addition in this case is highly stereoselective because the shape of the bicyclic ring system provides a steric bias. In Entry 2, a primary phenylthiocar-bonate ester is used as the radical source. In Entry 3, the allyl group is introduced at a rather congested carbon. The reaction is completely stereoselective, presumably because of steric features of the tricyclic system. In Entry 4, a primary selenide serves as the radical source. Entry 5 involves a tandem alkylation-allylation with triethylboron generating the ethyl radical that initiates the reaction. This reaction was done in the presence of a Lewis acid, but lanthanide salts also give good results. 

The radical source must have some functional group X that can be abstracted by trialkylstannyl radicals. In addition to halides, both thiono esters and selenides are reactive. Allyl tris(trimethylsilyl)silane can also react similarly.232 Scheme 10.11 illustrates allylation by reaction of radical intermediates with allylstannanes. 

Reactions of Radical Intermediates Derived from Ethanol... 

One aspect of both EPR and CIDNP studies that should be kept in mind is that either is capable of detecting very small amounts of radical intermediates. This sensitivity makes both techniques quite useful, but it can also present a pitfall. The most prominent features of either EPR or CIDNP spectra may actually be due to radicals that account for only minor amounts of the total reaction process. An example of this was found in a study of the decomposition of trichloroacetyl peroxide in alkenes. 

EPR studies and other physieal methods have provided the basis for some insight into the detailed geometiy of radieal species.Deduetions about strueture ean also be drawn from the study of the stereoehemistiy of reactions involving radical intermediates. Several structural possibilities must be considered. If discussion is limited to alkyl radicals, the possibilities include a rigid pyramidal structure, rapidly inverting pyramidal structures, or a planar structure. 

Intramolecular addition reactions are quite common when radicals are generated in molecules with unsaturation in a sterically favorable position. Cyclization reactions based on intramolecular addition of radical intermediates have become synthetically useful, and several specific cases will be considered in Section 10.3.4 of Part B. 

There are very few homolytic reactions on triazolopyridines. A suggestion that the ring opening reactions of compound 1 involved free radical intermediates is not substantiated (98T9785). The involvement of radical intermediates in additions to ylides is discussed in Section IV.I. The reaction of radicals with compound 5 and its 1-substituted derivatives gives 4-substituted compounds such as 234 (96ZOK1085). A more detailed study of the reaction of the 1-methyl and 1-phenyl derivatives with r-butanol and ammonium persulfate produced 4-methyl substitution with a silver nitrate catalyst, and the side chain alcohol 235 without the catalyst (96ZOK1412). 

Much of the interpretation of electroorganic reactions has assumed the model implied in the above discussion, i.e. conversion of the neutral substrate into a radical ion followed by distinct chemical and/or electrochemical steps. It follows therefore that specific structural effects should be found in the reactions of the intermediates. 

Secondly, the rates and modes of reaction of the intermediates are dependent on their detailed structure. For example, the stability of the cation radical formed by the oxidation of tertiary aromatic amines is markedly dependent on the type and degree of substitution in the p-position (Adams, 1969b Nelson and Adams, 1968 Seo et al., 1966), and the rate of loss of halogen from the anion radical formed during the reduction of haloalkyl-nitrobenzenes is dependent on the size and position of alkyl substituent and the increase in the rate of this reaction may be correlated with the degree to which the nitro group is twisted out of the plane of the benzene ring (Danen et al., 1969). 

In the anodic decarboxylation of phenylacetic acid benzaldehyde is the major product (80%) at low current density (< 3.2mA/cm ). Its formation is supposed to occur by reaction of the intermediate benzyl radical with oxygen, which is possibly simultaneously generated at the anode [31]. 

A more practical, atom-economic and environmentally benign aziridination protocol is the use of chloramine-T or bromamine-T as nitrene source, which leads to NaCl or NaBr as the sole reaction by-product. In 2001, Gross reported an iron corrole catalyzed aziridination of styrenes with chloramine-T [83]. With iron corrole as catalyst, the aziridination can be performed rmder air atmosphere conditions, affording aziridines in moderate product yields (48-60%). In 2004, Zhang described an aziridination with bromamine-T as nitrene source and [Fe(TTP)Cl] as catalyst [84]. This catalytic system is effective for a variety of alkenes, including aromatic, aliphatic, cyclic, and acyclic alkenes, as well as cx,p-unsaturated esters (Scheme 28). Moderate to low stereoselectivities for 1,2-disubstituted alkenes were observed indicating the involvement of radical intermediate. 

Several of these features remain unexplained but it is clear that here we have an example of a relatively well-behaved reversible electron transfer reaction involving radical intermediates. 

Ketones are oxidatively cleaved by Cr(VI) or Mn(VII) reagents. The reaction is sometimes of utility in the synthesis of difunctional molecules by ring cleavage. The mechanism for both reagents is believed to involve an enol intermediate.206 A study involving both kinetic data and quantitative product studies has permitted a fairly complete description of the Cr(VI) oxidation of benzyl phenyl ketone.207 The products include both oxidative-cleavage products and benzil, 7, which results from oxidation a to the carbonyl. In addition, the dimeric product 8, which is suggestive of radical intermediates, is formed under some conditions. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

Evidence in support of radical intermediates with MMO from both M. capsulatus (Bath) and M. trichosporium 0B3b was reported from experiments in which substrate radicals were trapped during turnover (89, 90). The amount of trapped radical, however, was not quantified in these experiments. In other reports, no diffusable radical species were detected in reactions with MMO from M. trichosporium 0B3b (61). 

Physical studies of the hydroxylase have established the structural nature of the diiron core in its three oxidation states, Hox, Hmv, and Hred. Although the active site structures of hydroxylase from M. tri-chosporium OB3b and M. capsulatus (Bath) are similar, some important differences are observed for other features of the two MMO systems. The interactions with the other components, protein B and reductase, vary substantially. More structural information is necessary to understand how each of the components affects the others with respect to its physical properties and role in the hydroxylation mechanism and to reconcile the different properties seen in the two MMO systems. The kinetic behavior of intermediates in the hydroxylation reaction cycle and the physical parameters of intermediate Q appear similar. The reaction of Q with substrate, however, varies. The participation of radical intermediates is better established with the M. triehosporium... 

An experimental probe for the presence of radical intermediates resulting from thermally induced homolytic cleavage of the N-0 bond was derived by incorporating an alkene into a model substrate to act as a potential intramolecular radical trap (Scheme 6.25) [11]. In a control experimental, thermal reaction of 73 gave the desired product 74 in 66% isolated yield. On the other hand, thermal rearrangement of the unsaturated compound 75 under our typical conditions gave the desired hydroxypyrimidinone 76 in only 38% isolated yield. When the vinyl ami-doxime mixture 75Z/E was heated in o-xylene at 125 °C in the presence of a... 

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