Electron-rich substrates

In contrast to the acyl- and sulfonylnitrenes described in this section, arylnitrenes produced thermally or photolytically from aryl azides, including those bearing strongly electron-withdrawing substituents (e.g., CN, N02, CF3), fail to promote ring expansion of arenes to 1H-azepines, although intermolecular substitution of electron-rich substrates, e.g. mesitylene and A.TV-dimethylaniline, have been noted.167... 

Aromatic nitrosation with nitrosonium (NO + ) cation - unlike electrophilic nitration with nitronium (NO ) cation - is restricted to very reactive (electron-rich) substrates such as phenols and anilines.241 Electrophilic nitrosation with NO+ is estimated to be about 14 orders of magnitude less effective than nitration with N02+. 242 Such an unusually low reactivity of NO+ toward aromatic donors (as compared to that of NO ) is not a result of the different electron-acceptor strengths of these cationic acceptors since their (reversible) electrochemical reduction potentials are comparable. In order to pinpoint the origin of such a reactivity difference, let us examine the nitrosation reaction in the light of the donor-acceptor association and the electron-transfer paradigm as follows. 

Weak nucleophile-electrophile interactions (and the donor-acceptor complexes) are considered precursors in aromatic electrophilic substitutions133 and in additions of electrophiles to C=C double bond of olefins the first step (the addition of the electrophile to an electron-rich substrate) is probably the same for both reactions. 

In addition to reactions characteristic of carbonyl compounds, Fischer-type carbene complexes undergo a series of transformations which are unique to this class of compounds. These include olefin metathesis [206,265-267] (for the use as metathesis catalysts, see Section 3.2.5.3), alkyne insertion, benzannulation and other types of cyclization reaction. Generally, in most of these reactions electron-rich substrates (e.g. ynamines, enol ethers) react more readily than electron-poor compounds. Because many preparations with this type of complex take place under mild conditions, Fischer-type carbene complexes are being increasingly used for the synthesis [268-272] and modification [103,140,148,273] of sensitive natural products. 

However, reactions with the more electron-rich substrate MoBr(CO)(dppe)Cp and HCsCC=CH were rather less successful, and the terminal diynyl complex was isolated in only moderate yield. Deprotonation of the latter was achieved with LiBu or LiNPr 2, the resulting lithio derivative being trapped with SiClMe3. 

For electron-rich substrates, nature often uses flavin-dependent halogenases (e.g. chlorotetracycline), vanadium haloperoxidases (snyderol, Figure 7.4) or heme-iron haloperoxidases (tetraiodothyronine. Figure 7.4) for this role (Figure 7.5). For electron-deficient molecules such as alkanes, mononuclear iron... 

The DCA-sensitized photooxygenation of electron-rich substrates is markedly accelerated (3-10 times) by the addition of biphenyl (BP), which acts as an effective one-electron carrier from the substrate to the excited state of the acceptor (equations 6 and 7). 

For the preparation of cyclic peroxides from less electron-rich substrates, addition of some metal salts (MX) with non-nucleophilic anions that can support solvolysis, is beneficial (equation 8). 

Early studies of these complexes focused primarily on the investigation of their oxygen-atom-transfer reactivity. Relatively little success was achieved, however. The peroxo fragments in these complexes exhibit nucleophilic character, and, therefore, they are generally ineffective oxidants for reactions with synthetically interesting electron-rich substrates such as alkenes and sulfides. Most of the known reactivity involves electrophilic substrates that, in many cases, insert into the Pd-0 bond of peroxopalladium(II) species (Fig. 4) [105,118]. 

It has been shown that 1-fluoroquinuclidinium fluoride (NFQNF, 2), one of the more successful N-F fluorinating agents, can fluorinate a wide array of electron-rich substrates.73,84-86 NFQNF (2) acts as a site-selective electrophilic fluorinating agent towards carbanionic substrates.73-75... 

The most serious limitation of TEMPO-mediated oxidations under Anelli s conditions is posed by the presence of HOC1—generated in situ— as a secondary oxidant, a quite reactive chemical that adds to olefins and produces electrophilic chlorination in many electron-rich substrates. 

Correa PE, Hardy G, Riley DP. Selective autoxidation of electron-rich substrates under elevated oxygen pressures. J Org Chem 1988 53 1695-1702. 

In the second step meto-chloroperbenzoic acid (MCPBA) epoxidizes the resulting bis-acetal from the /J-face. The weak 0-0 bond of MCPBA undergoes attack by electron rich substrates like alkenes. This reaction is syn stereospecific and believed to take place via transition state 48.30... 

The chemical reactivity most associated with dioxiranes is the electrophilic transfer of oxygen to electron-rich substrates (e.g., epoxidation, N-oxidation) as well as oxygen insertion reactions into unactivated C-H bonds. The reactivity-selectivity relationships among these types of reactions has been examined in depth by Curci. The reaction kinetics are dependent upon a variety of factors, including electron-donor power of the substrate, electrophilicity of the dioxirane, and steric influences (95PAC811]. 

In an another mechanistic study, Foote and co-workers reported a possible charge-transfer mechanism for the photochemical [2+2] cycloadditions of electron-rich ynamines [56-58]. Further studies on the regio- and stereoselectivity upon addition of less electron-rich substrates such as alkyl-substituted 1,3-bu-tadienes [59], acyclic enones [60], and aryl alkenes [61] to C60 were performed in more recent years. 

The effect of the electronic properties of the substituted benzaldehydes (la-c) on the allylation reaction is another interesting issue. Whilst the majority of catalysts shown in Figures 7.1 and 7.2 generally exhibit rather minor variation of the ee-value (typically with less than 20% difference between the electron-rich and electron-poor aldehydes), METHOX (22) appears to be a particularly tolerant catalyst, exhibiting practically the same enantioselectivity (93-96% ee Table 7.2, entries 1-3) and reaction rate across the range of substrates [28b, 29]. By contrast, QUINOX (24) stands on the opposite side of the spectrum, showing the most dramatic differences between the electron-poor and electron-rich substrate aldehyde (12-96% ee entries 4-6) [30]. 

A select number of transition metal compounds are effective as catalysts for carbenoid reactions of diazo compounds (1-3). Their catalytic activity depends on coordination unsaturation at their metal center which allows them to react as electrophiles with diazo compounds. Electrophilic addition to diazo compounds, which is the rate limiting step, causes the loss of dinitrogen and production of a metal stabilized carbene. Transfer of the electrophilic carbene to an electron rich substrate (S ) in a subsequent fast step completes the catalytic cycle (Scheme I). Lewis bases (B ) such as nitriles compete with the diazo compound for the coordinatively unsaturated metal center and are effective inhibitors of catalytic activity. Although carbene complexes with catalytically active transition metal compounds have not been observed as yet, sufficient indirect evidence from reactivity and selectivity correlations with stable metal carbenes (4,5) exist to justify their involvement in catalytic transformations. 

Shi and coworkers found that vinyl acetates 68 are viable acceptors in addition reactions of alkylarenes 67 catalyzed by 10 mol% FeCl2 in the presence of di-tert-butyl peroxide (Fig. 15) [124]. (S-Branched ketones 69 were isolated in 13-94% yield. The reaction proceeded with best yields when the vinyl acetate 68 was more electron deficient, but both donor- and acceptor-substituted 1-arylvinyl acetates underwent the addition reaction. These reactivity patterns and the observation of dibenzyls as side products support a radical mechanism, which starts with a Fenton process as described in Fig. 14. Hydrogen abstraction from 67 forms a benzylic radical, which stabilizes by addition to 68. SET oxidation of the resulting electron-rich a-acyloxy radical by the oxidized iron species leads to reduced iron catalyst and a carbocation, which stabilizes to 69 by acyl transfer to ferf-butanol. However, a second SET oxidation of the benzylic radical to a benzylic cation prior to addition followed by a polar addition to 68 cannot be excluded completely for the most electron-rich substrates. 

---