Nucleophiles carbon-based

Highly stabilized phosphorus ylides are prepared from acetylenic esters, a carbon-based nucleophile, and triphenylphosphine in aqueous media.40 In acetone-water (2 1) solvent, the reaction proceeds via the conjugate addition of triphenylphosphine to dialkyl acetylenedicarboxy-lates the resulting vinyl triphenylphosphonium salts undergo Michael addition reaction with a carbon-nucleophile to give the corresponding highly stabilized phosphorus ylides. 

The chlorine atom of 43 may be displaced readily by carbon-based nucleophiles with predominant overall retention of configuration at the phosphorus atom, similar to that observed in pentacoordinated analogues [37, 38], In some reactions, unselective substitution was observed [39], This approach was successfully applied for the... 

Nucleophilic reactions at the carbon atoms of 1,3,4-thiadiazoles occur readily owing to the electron-deficient nature of this ring. Halo-substituted thiadiazoles are therefore highly activated and react with a wide range of nucleophiles. Carbon-based nucleophiles such as malonates have been used in the synthesis of 2-substituted thiadiazoles. When chlorothiadiazole 52 was treated with ethyl acetate in the presence of NaHMDS, the 2-phenyl-1,3,4-thiadiazol-5-ylacetic ester 53 was obtained (Equation 6) <20060L1447>. 

Various nucleophiles, such as alcohols, fluoride ion, amides, allylsilane, and electron-rich aromatic rings, have been successfully used in this reaction in either an inter- or intra-molecular mode. A recent example of a new C-C bond formation in this reaction in the inter-molecular mode includes the preparation of derivatives 17 by the oxidation of 2-alkoxynaphthols 16 in the presence of an allylsilane or a silyl enol ether as a carbon-based nucleophile (Scheme 7) [22]. 

The construction of complex intermediates from simple and readily available starting materials has been accomplished using the electrocyclic ring-opening reaction of halocyclopropanes. This is typically achieved through interception of the cationic haloallyl intermediate by solvent, the silver(I) counteranion, or some alternate tethered heteroatom or carbon-based nucleophile. Examples of these processes are described below. 

The silver(I)-mediated ring opening of halocyclopropanes has been used to construct complex frameworks through the inter- and intramolecular trapping of cationic intermediates with heteronucleophiles. An obvious extension of this work is the involvement of carbon-based nucleophiles to form new carbon-carbon bonds. In 1996, Kostikov and coworkers reported the participation of aromatic solvents in the capture of halocyclopropane-derived allyl cations even in the absence of silver(I).30 However, this early example of intermolecular attack by a carbon nucleophile is one of very few such reports. In the same year, Gassman et al. reported cationic cyclizations of gem-dibromocyclopropanes tethered to remote diene moieties (Scheme 4.16).31... 

The oxidative activation of arenes is a powerful and versatile synthetic tactic that enables dearomatization to give useful synthons. Central to this chemistry are hydroxylated arenes or arenols, the phenolic functions of which can be exploited to facilitate the dearomatizing process by two-electron oxidation. Suitably substituted arenols can hence be converted, with the help of oxygen- or carbon-based nucleophiles, into ortho-quinone monoketals and ortho-quinols. These 6-oxocyclohexa-2,4-dienones are ideally functionalized for the construction of many complex and polyoxygenated natural product architectures. Today, the inherent and multiple reactivity of arenol-derived ortho-quinone monoketals and ortho-quinols species is finding numerous and, in many cases, biomimetic applications in modern organic synthesis. 

Arenols 4 and their conjugate arenolate bases are both (a) oxygen- and (b) carbon-based nucleophiles, which react with a wide range of electrophilic reagents (Figure 3). Their reactions with soft electrophiles can lead directly to cyclohexadienone derivatives this is the case, for example, with electrophilic halogenation, which effectively occurs at the electron-rich carbon centers (4 —> 5b) [29, 30]. 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

Carbon-based nucleophiles 1.03.3.2.4. Intermolecular addition reactions... 

SCHEME 6.54 Other metallated carbon-based nucleophiles approach carbonyl groups from equatorial trajectories. 

SCHEME 6.55 Carbon-based nucleophiles open epoxides according to the Fiirst-Plattner rule. 

The reaction of carbon-based nucleophiles and carboxylic acid derivatives often presents a sophisticated problem in reaction chemoselectivity, especially when selective acylation of organometallics to form a ketone is required (equation 1). Historically, this transformation has been plagued by the formation of by-products due to subsequent nucleophilic addition to the desired product. A great deal of effort has been directed toward developing gentler techniques which avoid overaddition. Alternatively, the preparation of a ketone ft om a carboxylic acid equivalent often relies on a three-step approach, as shown in equation (2). 

Baldwin, J.E., Adhngton, R.M., Russell, A.T., and Smith, M.L., Carbon based nucleophilic ring opening of activated monocyclic P-lactams. Synthesis and stereochemical assignment of the ACE inhibitor WE-10129. Tetrahedron, 51, 4733, 1995. 

The stereochemistry of nucleophilic attack is consistently trans to the metal-alkene bond (Scheme 39, equation 19). Theregiochemistry of attack is normally at the alkene carbon bearing the most electron-donating (or least electron-withdrawing) group. For weakly electron-donating substituents, such as alkyl, the observed regioselection is modest for carbon-based nucleophiles. For amine and... 

Coordination of a metal to the itt-orbitals of an arene opens pathways for nucleophile addition to the arene. The power of the effect is related to the oxidation state (Cr°, Mn Fe ) and peripheral ligands (Cp or CO). Under suitable conditions, both heteroatom and carbon-based nucleophiles add rapidly under mild conditions. The fate of the cyclohexadienyl intermediate depends on the conditions of the next stage of the batch-wise process. Loss of an electronegative leaving group leads to an analog of... 

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