C -electrophiles

Thus in neutral medium the reactivity of 2-aminothiazoles derivatives toward sp C electrophilic centers usually occurs through the ring nitrogen. A notable exception is provided by the reaction between 2-amino-thiazole and a solution (acetone-water, 1 1) of ethylene oxide (183) that yields 2-(2-hydroxyethylamino)thiazole (39) (Scheme 28), Structure 39... 

All the examples of reactivity in acidic medium (Scheme 40) involve a reagent with a sp C hybridized electrophilic center, but the actual reactive species generated bears a sp C electrophilic center. In this case, exocyclic N-alkylation is not surprising (see Section III.2). 

Reactions with Reagents Bearing an sp C Electrophilic Center... 

C. Electrophiles capable of substituting only strongly activated aromatic rings ... 

C. Electrophilic Substitution of Compounds Containing Several Thiophene Rings... 

III. TWO-COMPONENT METHODS A. S-Substitutlon of Sulfinate Nucleophiles with C-Electrophiles... 

Structure B is of most interest. It is responsible for the activity of nitronates as 1,3-dipoles in [3+ 2]-cycloaddition reactions. This is the most important aspect of the reactivity of nitronates determining the significance of these compounds in organic synthesis (see e.g., Ref. 267). In addition, this structure suggests that nitronates can show both, O -nucleophilic properties, that is, react at the oxygen atom with electrophiles, and a-C-electrophilic properties, that is, add nucleophiles at the a-carbon atom. 

The resonance structures of nitronates are most similar to those of nitrones, but nitronates have the additional structure D. Strange as it may seem, the contribution of this structure more likely slightly diminishes a-C-electrophilic activity of nitronates, move than is favorable for the appearance of the nucleophilic properties. In any case, no transformations, in which nitronates unambiguously act as C-nucleophiles, have been rigorously established. 

The addition of electrophiles at the oxygen atom could activate nitronates as C-electrophiles, analogously to that in the case of the carbonyl group (297). However, this aspect of reactivity of nitronates has remained unknown until very recent times. 

The diastereoselective alkylation of dialkyl malates has been frequently used in the past [65]. However, according to the original procedure [63] (dialkyl malate, base, -78 -20 °C, then -78 °C, electrophile, then -78 0 °C, 16 h), the alkylation proceeded in average yields of about 50-60% and in diastereoselectivities in the range of 9 1 anti / syn. In our hands, application of this procedure to the reaction of benzyl bromide 23 with dimethyl malate 106 produced the alkylated compounds in only 20% yield. The yield of the alkylation was easily improved (>75%) when the ester was deprotonated with LHMDS in the presence of the electrophile at -78 °C and the reaction mixture was allowed to warm to 10 °C (Scheme 26 and Table 2). 

Phenol-induced oxidative stress mediated by thiol oxidation, antioxidant depletion, and enhanced free radical production plays a key role in the deleterious activities of certain phenols. In this mode of DNA damage, the phenol does not interact with DNA directly and the observed genotoxicity is caused by an indirect mechanism of action induced by ROS. A direct mode of phenol-induced genotoxicity involves covalent DNA adduction derived from electrophilic species of phenols produced by metabolic activation. Oxidative metabolism of phenols can generate quinone intermediates that react covalently with N-1,N of dG to form benzetheno-type adducts. Our laboratory has also recently shown that phenoxyl radicals can participate in direct radical addition reactions with C-8 of dG to form oxygen (O)-adducts. Because the metabolism of phenols can also generate C-adducts at C-8 of dG, a case can be made that phenoxyl radicals display ambident (O vs. C) electrophilicity in DNA adduction. 

---