Electrophilic acetylene reactivity

The nitrogen atoms in ADC compounds are highly electrophilic. Nucleophilic attack on nitrogen is easy, and as with electrophilic acetylenes, such as dimethyl acetylenedicarboxylate, it seems likely that some cycloaddition reactions of ADC compounds with unsymmetrical substrates proceed via a stepwise mechanism. PTAD is a powerful electrophile, although TCNE is more reactive, and chlorosulfonyl isocyanate is more reactive still.58... 

The original meaning of the term has been extended to the reversal of any commonly accepted reactivity pattern. For example, reaction of R-C=CX (X = halide) as a synthon for "R-C=C+ (i.e., electrophilic acetylene) is an umpolung of the normal, more common acetylide, R-C=(T (i.e., nucleophilic) reactivity. 

Donor substituents on the vinyl group further enhance reactivity towards electrophilic dienophiles. Equations 8.6 and 8.7 illustrate the use of such functionalized vinylpyrroles in indole synthesis[2,3]. In both of these examples, the use of acetyleneic dienophiles leads to fully aromatic products. Evidently this must occur as the result of oxidation by atmospheric oxygen. With vinylpyrrole 8.6A, adducts were also isolated from dienophiles such as methyl acrylate, dimethyl maleate, dimethyl fumarate, acrolein, acrylonitrile, maleic anhydride, W-methylmaleimide and naphthoquinone. These tetrahydroindole adducts could be aromatized with DDQ, although the overall yields were modest[3]. 

Reactions of alkynes with electrophiles are generally similar to those of alkenes. Because the HOMO of alkynes (acetylenes) is also of n type, it is not surprising that there IS a good deal of similarity between alkenes and alkynes in their reactivity toward electrophilic reagents. The fundamental questions about additions to alkynes include the following. How reactive are alkynes in comparison with alkenes What is the stereochemistry of additions to alkynes And what is the regiochemistry of additions to alkynes The important role of halonium ions and mercurinium ions in addition reactions of alkenes raises the question of whether similar species can be involved with alkynes, where the ring would have to include a double bond ... 

The scope of the SH reaction encompasses sp-sp2 (alkenyl, aryl (29),143 heteroaryl) and sp-sp couplings (the modified Cadiot-Chodkiewicz reaction).142 Iodides are most frequently used as electrophilic coupling partners, though the use of bromides, triflates (30),144 or even some reactive chlorides (31)145 is also possible. Due to the low steric bulk of the acetylenic unit, as well as its exceptional ability in the transduction of electronic effects, the SH reaction is well suited for construction of new (e.g., star-like) molecular architectures through polysubstitution (32).146... 

Most reactive metabolites produced by CYP metabolic activation are electrophilic in nature, which means that they can react easily with the nucleophiles present in the protein side chains. Several functional groups are recurrent structural features in M Bis. These groups have been reviewed by Fontana et al. [26] and can be summarized as follows terminal (co or co — 1) acetylenes, olefins, furans and thiophenes, epoxides, dichloro- and trichloroethylenes, secondary amines, benzodioxoles (methylenediox-yphenyl, MDP), conjugated structures, hydrazines, isothiocyanates, thioamides, dithiocarbamates and, in general, Michael acceptors (Scheme 11.1). 

From the investigation of all these data it is clear that the aromaticity of phosphinine is nearly equal to that of benzene. Their chemical reactivity, however, is different. Most important is the effect of the in-plane phosphorus lone pair, which (i) is able to form a complex and (ii) can be attacked by electrophiles to form A -phosphinines. Thus, electrophilic substitution reaction on the ring carbon is impossible. In Diels—Alder reactions, phosphinines behave as dienes, providing similar products to benzene but under less forcing condition (the reaction with bis(trifluoromethyl) acetylene takes place at 100 °C with 3, while for benzene 200 °C is required). 

The organometallic chemistry of alkynylcyclopropanes involves primarily the formation and reactions of carbon-metal er-bonds. Metals come essentially from the main group elements, with lithium playing a major role. The two metallation sites are the cyclopropyl and the acetylenic positions, which are expected to differ considerably in their acidity values (t-butylacetylene, pKa = 25230, cyclopropane, pKa = 46183) but less in the reactivity of their metal conjugated bases towards electrophiles. 

Carbocations with trivalent carbon may have carbon with coordination number 2. Acyl ions have already been mentioned the vinyl cations, or car-bynium ions (26), have been detected as intermediates in addition of electrophiles to acetylenes and allenes and in solvolysis reactions with the highly reactive trifluoromethanesulfonate (triflate) leaving group.84 Vinyl cations are expected... 

To the extent that the enolate resulting from conjugate addition at the (3-carbon can be stabilized, the rate of this reaction pathway is enhanced. For example, (3-Michael additions are observed for MVK, acrolein, and acetylenic electrophiles even without the presence of a Lewis acid. Furthermore, MVK reacts with the 2,5-dimethylpyrrole complex (22) to form a considerable amount of (3-alkylation product, whereas only cycloaddition is observed for methyl acrylate. The use of a Lewis acid or protic solvent further enhances the reactivity at the (3-position relative to cycloaddition. While methyl acrylate forms a cycloadduct with the 2,5-dimethylpyrrole complex (22) in the absence of external Lewis acids, the addition of TBSOTf to the reaction mixture results in exclusive conjugate addition (Tables 3 and 4). 

Hexafluoroacetone is a reactive electrophile. It reacts with activated aromatic compounds (e.g., phenol), and can be condensed with olefins, dienes, ketenes, and acetylenes. It forms adducts with many compounds containing active hydrogen (e.g., H.,0 or HCN). Reduction of HFA with NaBH or LiAlH affords the useful solvent hexafluoroisopropyl alcohol. The Industrial importance of HFA arises largely from its use 1n polymers and as an... 

Bis(trifluoromethyl)diazomethane is a reactive, electrophilic compound. It forms adducts with nucleophiles such as amines and phosphines5 and adds to olefins, acetylenes,5 and thiocar-bonyl compounds6 to form heterocycles. It has been used as a source of bis(trifluoromethyl) carbene in reactions with benzene,5 saturated hydrocarbons,7 carbon disulfide,8 and transition metal compounds,8 and it undergoes a unique radical chain reaction with saturated hydrocarbons to form adducts that are hydrazoncs and azines.7... 

---