Nucleophilicity at carbon

In situation (a) a strong carbon-metal bond results. To this group belong the typical Schrock-type carbenes [e.g. Np3Ta=CH(7Bu)], many of which are nucleophilic at carbon. Situation (b) should also lead to nucleophilic carbene complexes, albeit with a weaker carbon-metal bond. Typical reactions of nucleophilic carbene complexes include carbonyl olefination (Section 3.2.4) and olefin metathesis (Section 3.2.5). 

Most experimental data suggest that the actual methylenating agent derived from the Tebbe reagent upon treatment with a weak base, is the highly reactive carbene complex Cp2Ti=CH2 [709]. This complex is a typical Schrock-type carbene, because it is high-valent [Ti(IV)], electron-deficient (16 valence electrons) and nucleophilic at carbon. 

The nucleophilic attack of organometallic species occurs with cleavage of the N—S bond and eventual formation of an a-diketone. This reaction has been shown to proceed through an unsym-metrical diimine (17) (Scheme 2) <90JHC1861>. The 4-unsubstituted series (18) can be functionalized in this way. The diimine product of ring opening (19) can add a nucleophile at carbon (20) and then be recyclized to a 3,4-disubstituted 1,2,5-thiadiazole (21) (Scheme 3) <86H1131>. 

Three groups of polar processes to form aziridines are shown in Scheme 16. In every case, each of the two reactants must be capable of acting formally as either a bis-nucleophile or a bis-electrophile, or they must each have both nucleophilic and electrophilic character. In the aza-Darzens route (B-83MI 101-01, 84CHEC-(7)47), the imine acts as an electrophile at carbon and later as a nucleophile at nitrogen, while the a-haloenolate acts initially as a nucleophile at carbon and later as an electrophile at the same carbon. The roles of the two components are reversed for the polar aziridination route, which is related to the epoxidation reaction. In the last route, the 1,2-dihalide or a-haloenone acts formally as a bis-electrophile while the amine acts as a bis-nucleophile. 

The acetyl-substituted complexes, initially prepared by Jager36 by direct synthesis, have served as the basis for all of the work in this area. It has been shown that the acetyl group can be replaced by substitution, especially nitration, where reaction conditions are rather vigorous.39 The acetyl-substituted complexes are not only nucleophilic at carbon, a property exhibited in the above reaction, but they are also nucleophilic at oxygen, being vinylogous amides, and undergo... 

We now wish to discuss displacements by nucleophilic reagents (Y ) on alkyl derivatives (RX). These are ionic or polar reactions involving attack by a nucleophile at carbon. A typical example is the reaction of hydroxide ion with bromomethane to displace bromide ion ... 

An SN2-type of attack of bromide ion, or other nucleophile, at carbon on the side opposite to the bridging group then results in formation of the antarafacial-addition product ... 

The attack of a nucleophile at carbon (Scheme 3) leads either to nucleophilic displacement (path a) or ring cleavage (path b), the latter being the most common result. Attempts to reduce 1,3,4-oxadiazoles to dihydro- and tetrahydro-1,3,4-oxadiazoles have failed. 

Problem 4.14 electrophilic cation, 4-79, reacts with a nucleophile at carbon to give... 

The reaction of amines with cyclopropenones appears to be extremely sensitive to the reaction conditions Ammonia reacts with diphenylcyclopropenone at room temperature to yield the isomeric /3-lactams 56 and 57, whereas the vinyl aldehyde 58 is produced at — 33°C. These results can be rationalized in terms of the intermediate 59 which would result from conjugate addition of the nucleophile at carbon (equation 56). 

The first carbene compound to be well characterized was prepared in 1966 and was one of many Fischer-Type Carbene Complexes io be reported (see equation 7). Fischer carbenes are characterized by heteroatom substituents at the carbene carbon, stabilization by a low-valent metal center, and a partial positive charge at the carbene carbon. In contrast, Schrock Type Carbene Complexes, or alkylidenes, that have alkyl substituents, are found on metal centers in higher oxidation states, and are nucleophilic at carbon. Many Fischer carbenes are known for chromium, whereas chromium alkylidenes are much less common. Monohalocarbenes of chromium, for example, (OC)5Cr=C(F)NEt2, have also been extensively investigated. Two carbene reactions of note for their application to organic synthesis are the cycloaddition of alkenes with carbene complexes and the reaction of aromatic carbenes with alkynes to yield complexed naphthols (the Dotz reaction ). ... 

Carbenes are defined as species containing divalent carbon [1], and they may display either electrophilic or nucleophilic reactivity depending on whether the two unshared electrons on the carbon center are unpaired (triplet carbene) or paired (singlet carbene). Metal-carbene complexes can be classified in a similar way based on their reactivity toward electrophiles and nucleophiles. The resonance forms shown in Fig. 4.1 define the limiting structures, and the formal charge on the carbene carbon indicates the preferred reactivity. Those that are nucleophilic at carbon are called Schrock-type complexes or alkylidenes, and they generally... 

Strongly backbonding metal -alkyl, hydrohen R groups -X2-type ligands -Nucleophilic at carbon... 

The mechanism of this reaction is only slightly more complicated than the usual reaction of nucleophiles with acid chlorides (p. 854). Diazo compounds are nucleophiles at carbon and add to the carbonyl group of the reactive acid chloride. Chloride ion is expelled in the elimination phase of this normal addition-elimination process. In the only new step of the reaction, chloride removes the newly acidic hydrogen to give the diazo ketone (Fig. 18.64).This hydrogen is acidic because the conjugate base is stabilized by resonance. 

It turns out that most enolates are better nucleophiles at carbon. So, alkylation takes place faster at carbon than at oxygen (Fig. 19.50). One explanation for this fact is that the highest occupied molecular orbital of the nucleophile has more electron density at the carbon than at oxygen. Selectivity might also be a result of coimter ion (Li, for example) coordination between the enolate and the electrophile. If the counterion is complexed with the site of overall higher electron density, the oxygen in this case, it sterically hinders alkylation at that position. 

How does the carbonyl group s structure (Section 17-2) help us understand the way it functions chemically We shall see that the carbon-oxygen double bond is prone to additions, just like the ir bond in alkenes. Being highly polar, however, it is predisposed toward attack by nucleophiles at carbon and electrophiles at oxygen. This section begins the discussion of the chenustry of the carbonyl group in aldehydes and ketones. 

Addition to aldehydes and ketones can be catalyzed by either acid or base. In acid solution, the first step is protonation of the carbonyl at oxygen. In base, the first step is attack of the nucleophile at carbon. 

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