Electrophilic carbon centers

It is well known that strong electrophiles such as carbocations are reduced by organosilicon hydrides (Eq. 1).3,70,71 On the other hand, simple mixtures of organosilicon hydrides and compounds with weakly electrophilic carbon centers such as ketones and aldehydes are normally unreactive unless the electrophilicity of the carbon center is enhanced by complexation of the carbonyl oxygen with Brpnsted acids3,70 73 or certain Lewis acids (Eq. 2).1,70,71,74,75 Using these acids, hydride transfer from the silicon center to carbon may then occur to give either alcohol-related or hydrocarbon products. 

A similar reaction pathway was found for the Sn2 substitution of an epoxide with a lithium cuprate cluster [124]. In contrast to that in the MeBr reaction, the stereochemistry of the electrophilic carbon center is already inverted in the transition state, providing the reason for the preferred trans-diaxial epoxide-opening widely observed in synthetic studies. The TS for the Sn2 reaction of cyclohexene oxide is shown in Eq. 10.12. 

In coordinatively saturated metal hydrides, such as the HM(CO)s (M => Cr, Mo, W) derivatives, formation of the four-centered transition state for C02 insertion (Scheme 1) may proceed with or without CO loss and concomitant coordination ofC02 at the metal center. That is, C02 insertion may occur by means of dissociative (D) or dissociative interchange (Id) processes, or an associative interchange (Ia) process (47, 48). In either instance an acid-base interaction between the anionic hydride ligand and the electrophilic carbon center of carbon dioxide as represented in 6 may occur prior to formation of the four-centered transition state depicted in Scheme 1. An interaction of this type has been observed for these HM(CO)j derivatives with Lewis acids such as BH3 (49). 

Molina et al. have described the reactivity of 2,4-diimino-l,3-diazetidinone which is attacked by several nucleophiles at the electrophilic carbon center <1993JPR305>. Some of these reactions are summarized in CHEC-II(1996) <1996CHEC-II(1B)911>. A few representative examples are shown in Scheme 18. 

Another method consists in generating an electrophilic carbon-centered radical (e.g. the CH3COCH2- radical from acetone, peroxydisulfate and Ag(I)) which, instead of reacting with the protonated heteroarene, readily adds to simple alkenes forming a radical adduct that, owing to its nucleophilic character, selectively reacts with the heterocyclic ring (Scheme 4) [2]. 

The overall changes in the chemical shift of the methine protons can be directly correlated with the amounts of ions if ionization is significant (>1%). However, even minute amounts of intermediate cations can be detected in some systems by dynamic NMR. Because ionization leads to the formation of a planar carbenium ion, the chirality at the carbon atom is lost. In the particular case of the isobutyl vinyl ether derivatives, the isobutoxy group has a built-in probe (CH2-CHMe2) separated from the chiral center by oxygen atom. The methylene protons on the ether group are magnetically nonequivalent due to the presence of four different substituents at the electrophilic carbon center. They become equivalent only... 

With various nitriles, two different hetero dinuclear complexes with arrangement (73) are obtained (equation 35). The formation of the cyclometalated species (79) involves a hydrogen transfer from a Cp methyl group to the electrophilic carbon center of the nitrile in an intermediate fiilvene complex. Kinetic results indicate that a second molecule of nitrile catalyzes the conversion of this fiilvene intermediate into (80). ... 

Conceptually, perhaps the simplest method of forming a a-bond between two carbon fragments is the reaction of a carbanion with an electrophilic carbon center. Nature relies heavily upon reactions of carb-... 

Activation of Leaving Groups. When the alkoxy oxygen atom is bound to a metal ion, its leaving ability from electrophilic carbon centers is enhanced, leading to catalysis in ester hydrolysis as exemplified by D (37). 

Baciocchi E, Muraglia E, Sleiter G (1992) Homolytic substitution reactions of electron-rich pentatomic heteroaromatics by electrophilic carbon-centered radicals. Synthesis of. alpha, heteroarylacetic acids. J Org Chem 57 6817-6820... 

Alper and Xiao [45] synthesized thiochromanones by palladiumotalyzed carbonylative ring-forming reactions of 2-iodothiophenol derivatives, allenes, and CO. The fhiochroman-4-ones were achieved in good to excellent isolated yields with high regioselectivity, which was probably caused by electronic effects (Scheme 1.24). This catalytic heteroannulation comprises the regioselective addition of the sulfur moiety on the more electrophilic carbon center of the allene, arylpalladium formation, CO insertion, subsequent intramolecular cydization, and, finally, the reductive elimination. 

Migration of a C—C or C—H bond that is centered on the ojq gen-bearing carbon and that occurs toward a vicinal electrophilic carbon center, generating a carbonyl group at the end of the process. 

As with alkene precursors, there is often a lack of selectivity in Schmidt reactions of carbocations generated from alcohols under acidic reaction conditions. However, the Renaud group reported the first example of an intramolecular Schmidt reaction involving a primary electrophilic carbon center for the synthesis of (-)-indolizidine under nonacidic conditions fScheme 4.1 liP After activation of the alcohol 31 via triflation, alkyl migration and extrusion of molecular N2 occurred smoothly. After subsequent reduction of 32, the desired structure 33 was obtained in high yield and excellent optical purity (98% ee). This concise approach enabled the synthesis of (-)-indolizidine in seven linear steps and 27% overall yield. 

The ease with which a given 8 2 displacement occurs depends on multiple factors, such as the nucleophilicity of the incoming nucleophile (which depends on both its electronic and steric character), steric hindrance at the electrophilic carbon center, the effectiveness of the leaving group, and the solvent and other environmental effects. By defining a standard substrate and standard reaction conditions, the reactivity of different nucleophiles may be quantified. One such measure of nucleophilicity is the Swain-Scott nucleophilicity constant n, for which methyl iodide is chosen as the standard substrate and reaction rates are measured in methanol at 25 °C ... 

Reaction of Trimethylsilylacetylene/Acetylide with Electrophiles. Deprotonation of TMSA with n-BuLi or Grignard reagents produces nucleophilic acetylides, which can react with various electrophilic carbon centers such as carbonyls, alkyl halides, or epoxides. 

Conclusion. Of a pair of nucleophiles containing the same reactive atom, the species with a negative charge is the more powerful nucleophile. Or, of a base and its conjugate acid, the base is always more nucleophilic. This finding is intuitively very reasonable. Because nucleophilic attack is characterized by the formation of a bond with an electrophilic carbon center, the more negative the attacking species, the faster the reaction should be. 

Large 5p orbital, polarized toward electrophilic carbon center... 

Alkali metal fluorides are well known as traditional halogen exchange or nucleophilic substitution reagents (7-5). Typically polar aprotic solvents such as dimethylformamide, A, A dimethylacetamide, acetonitrile, tetrahydrofuran, glymes, etc. are required. In addition, crown ethers are often added to increase the solubility of the alkali metal fluorides and thereby the halogen exchange reaction rate. The order of reactivity is Cs > Rb > K > Na for the alkali metals and lo > 2 for the electrophilic carbon center. 

In theory, it should also be possible to prepare dithiocarbamate complexes in this manner from anionic metal sulfides, upon nucleophilic attack of the sulfide at the electrophilic carbon center (Eq. 32). 

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