Cyano carbon centers, nucleophilic

In the absence of heteroatom containing substituents (e.g. halo-, cyano-), at or conjugated with the radical center, carbon-centered radicals have nucleophilic character. Thus, simple alkyl radicals generally show higher reactivity toward electron-deficient monomers (eg. acrylic monomers) than towards electron-rich monomers (e.g, VAc, S) - Table 3.6. 

Nucleophilic substitution reactions of aniline are also studied at tertiary alkyl carbon centers in MeCN66. The reactions with 2-cyano-2-propyl, 5, and 1-cyanooctyl, 6, arenesulfonates are reported in MeCN at 50.0 °C. 

Nucleophilic attack of aniline also occurs at a cyano (nitrile) carbon center. Williams and coworkers97 have reported on the anilinolysis of dicyanamide (equation 10). 

The destabilization of sp -bound fluorine by p-jt repulsion activates fluorinated aromatic compounds totvard nucleophilic attack and subsequent substitution. The susceptibility of the carbon center toward nucleophiles is also enhanced by the negative inductive (—T) effect of fluorine. In particular, if the aromatic compound is also activated by —M electron-withdrawing substituents, for example a nitro or cyano group, in the ortho or para positions the fluorine is easily replaced by a variety of nucleophiles even under very mild conditions via a resonance stabilized Meisenheimer complex (Scheme 2.39). The ease of nucleophilic halogen replacement - F > Cl > Br > I - is in the opposite order to that for aliphatic nucleophilic substitution. 

Despite their overall electtical neutrality, carbon-centered radicals can show pronounced electrophilic or nucleophilic character, depending on the substituents present. " This electrophilic or nucleophilic character is reflected in rates of reaction with nonradical species, for example, in additions to substituted alkenes. Alkyl radicals and a-alkoxyalkyl radicals are distinctly nucleophilic in character and react most rapidly with alkenes having EWG substituents. Even methyl radicals with a single EWG, such as t-butoxycarbonyl or cyano are weakly nucleophilic. Radicals having two EWGs, such as those derived from malonate esters, react preferentially with double bonds having ERG substituents. Perfluoro radicals are electiophilic and are about 10 more reactive than alkyl radicals. ... 

Many variations of this route involve the formation of the 2,3-bond of a thiophene by the 2-carbon atom acting as a nucleophilic center in an intramolecular addition to a carbonyl or a cyano group . Examples are shown in Schemes 88 <2002TL257> and 89 <2003T1557>. 

Formation of Carbon-Nitrogen Bonds A ring closure of this type will most often involve either the attack of an electrolytically formed nucleophile (hydroxylamine, amine, or hydrazine) on an electrophilic center (existing or potential carbonyl, cyano, nitro, or nitroso group) or a reaction between a nucleophile and an electrolytically generated electrophilic center (e.g., nitroso group or carbonium ion). 

Similarly, the nucleophilic substitution at sulfur in [(—)-menthyl] (A)-4-methylbenzenesul-finate by prostereogenic a-metalated nitriles yields the corresponding a-cyano sulfoxides 3 as diastereomeric mixtures. On oxidation these are converted to the corresponding sulfones with a stereogenic center at the a-carbon atom only73. 

In 2012, Alexakis and co orkers disclosed the first stereoselective annulation reaction between ynals and a-cyano-l,4-diketones which is mediated by a catalytic amount of a triazolium salt precatalyst and a weak carboxylate base. This transformation proceeds smoothly under mild reaction conditions and generates three contiguous stereogenic centers, one of which is a quaternary acetal carbon, and affords privileged bicyclic scaffolds in 61-90% yields with up to 20 1 diastereomeric preference. A mechanistic rationalization for the NHC-catalyzed annulation of a-cyano-l,4-diketones with ynals is proposed as the following. Initially, the free carbene condenses with a molecule of ynal to form the key d,p-unsaturated acylazolium intermediate followed by a direct nucleophilic conjugate addition of 1,4-diketone. Subsequent intramolecular H-migration and an irreversible lactonization furnish the observed bicyclic product and liberate free carbene for the next catalytic cycle (Scheme 7.98). 

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