Carbon reaction with nucleophile

TT-Aliylpalladium chloride reacts with a soft carbon nucleophile such as mal-onate and acetoacetate in DMSO as a coordinating solvent, and facile carbon-carbon bond formation takes place[l2,265], This reaction constitutes the basis of both stoichiometric and catalytic 7r-allylpalladium chemistry. Depending on the way in which 7r-allylpalladium complexes are prepared, the reaction becomes stoichiometric or catalytic. Preparation of the 7r-allylpalladium complexes 298 by the oxidative addition of Pd(0) to various allylic compounds (esters, carbonates etc.), and their reactions with nucleophiles, are catalytic, because Pd(0) is regenerated after the reaction with the nucleophile, and reacts again with allylic compounds. These catalytic reactions are treated in Chapter 4, Section 2. On the other hand, the preparation of the 7r-allyl complexes 299 from alkenes requires Pd(II) salts. The subsequent reaction with the nucleophile forms Pd(0). The whole process consumes Pd(ll), and ends as a stoichiometric process, because the in situ reoxidation of Pd(0) is hardly attainable. These stoichiometric reactions are treated in this section. 

The LUMO, which is the frontier orbital in reactions with nucleophiles, has a larger coefficient on the /3-carbon atom, whereas the two occupied orbitals are distorted in such a way as to have larger coefficients on oxygen. The overall effect is that the LUMO is relatively low-lying and has a high coefficient on the /3-carbon atom. The frontier orbital theory therefore predicts that nucleophiles will react preferentially at the /3-carbon atom. 

We saw in the preceding chapter that the carbon-ha]ogen bond in an alkyl halide is polar and that the carbon atom is electron-poor. Thus, alkyl halides are electrophiles, and much of their chemistry involves polar reactions with nucleophiles and bases. Alkyl halides do one of two things when they react with a nucleophile/base, such as hydroxide ion either they undergo substitution of the X group by the nucleophile, or they undergo elimination of HX to yield an alkene. 

It has long been known that a, / -unsaturated sulfones resemble a, /i-unsaturated ketones and aldehydes in undergoing addition reactions with nucleophilic reagents43. These reactions are initiated by nucleophilic attack at the carbon to the sulfone group ... 

Nitroalkenes with potential leaving groups in (3-position such as a dialkylamino, an alkylthio, or a phenylsulfonyl group undergo addition-elimination reactions with nucleophiles. The chemistry of nitroenamines has been extensively investigated, and their potential utility in organic synthesis has been well established.2613 116 Severin and coworkers have developed the addition of elimination reactions of nitroenamines with carbon nucleophiles in 1960-1970, as exemplified in Eq. 4.94.117... 

Iodomethyltrialkyltin compounds, R3SnCH2I (from R3SnCl and ICH2ZnI), provide an entry to other functionally substituted organotin compounds. Reaction with nucleophiles such as R10, R1S, R 2N, or R 3P gives further a-substituted derivatives, and carbon nucleophiles can be used to locate the functional groups at more distant positions on the alkyl chain. Some examples are shown in Scheme 3. 

Ring opening reaction of alkylidenecyclopropanone acetals readily proceeds in the presence of Lewis or Bransted acids to produce l-alkylidene-2-oxyallyl cation, which is provided for the reaction with nucleophiles such as chloride, alcohols, siloxyalkenes, and furans. The reaction of this cation with the carbon nucleophiles gives products of [4 + 3] and [3 + 2] cycloaddition as well as those of nucleophilic addition. The modes of addition reactions are controlled by the oxy group of the cation and by the reaction conditions including solvent. 

Lewis acid-acetal complexes in NMR studies, but never detected alkoxycarbenium ions.29 The absence of alkoxycarbenium ions in the spectra, however, does not necessarily rule out their intermediacy in the reactions with nucleophiles. Therefore, it was imperative to accomplish the reactions of spectroscopically characterized, nonstabilized alkoxycarbenium ions with carbon nucleophiles. The cation pool method made it possible and opened a new chapter in the chemistry of alkoxycarbenium ions. 

As mentioned above, the reactivity of alkoxyallenes is governed by the influence of the ether function, which leads to the expected attack of electrophiles at the central carbon C-2 of the cumulene. However, the alkoxy group also activates the terminal double bond by its hyperconjugative electron-withdrawing effect and makes C-3 accessible for reactions with nucleophiles (Scheme 8.3). This feature is of particular importance for cyclizations leading to a variety of heterocyclic products. The relatively high CH-acidity at C-l of alkoxyallenes allows smooth lithiation and subsequent reaction with a variety of electrophiles. In certain cases, deprotonation at C-3 can also be achieved. 

In general, vinylketene complexes 221 undergo reaction with nucleophiles at the ketene carbonyl carbon (C-l), yielding /3,y-unsaturated ketones (236).86 It is interesting to note that the analogous vinylketenimine complexes undergo nucleophilic attack at C-2.86 87 89 135 142... 

In addition to solvolysis and nitrenium ion formation, Af-aLkoxy-A-chloroamides (2) also undergo bimolecular reactions with nucleophiles at nitrogen. Not only is the configuration destabilized by the anomeric effect, it also parallels that of a-halo ketones, where halogen on an sp carbon is activated towards reactions by the adjacent carbonyl. This rate-enhancing effect on 8 /2 processes at carbon is well-known, and has been attributed to conjugation of the p-orbital on carbon with the carbonyl jr-bond in the S 2 transition state stabilization of ionic character at the central carbon as outlined by Pross as weU as electrostatic attraction to the carbonyl carbon. The transition states are also affected by the nature of the nucleophile. ... 

The meso-ionic l,3>2-oxathiazol-5-ones (169) show an interesting range of reactions with nucleophiles including ammonia, primary amines, and aqueous alkali. They also react with l,3-dipolarophiles, including dimethyl acetylenedicarboxylate and methyl propiolate, yielding isothiazoles (171) and carbon dioxide. 1,3-Dipolar cycloaddition reactions with alkenes such as styrene, dimethyl maleate, and methyl cinnamate also lead to isothiazoles (171) directly. BicycUc intermediates (cf. 136) were not isolable these cycloaddition reactions with alkenes giving isothiazoles involve an additional dehydrogenation step. 

The lactonic property of pyran-2-ones is apparent in their reactions with nucleophiles, which normally lead to ring opening. However, this may not be simply direct attack of the reagent at the carbonyl carbon. 

Quinoxalines substituted in the 5- or 6-position generally follow the pattern of reactions expected for substituted benzene derivatives, although recently there have been reports of interesting and unexpected reactions with nucleophiles (see Section III, A,2 and references 85-90). 6-Methylquinoxaline is brominated in the side chain when treated with N-bromosuccinimide in carbon tetrachloride in the presence of azobisiso-butyronitrile, to form 6-bromomethylquinoxaline.182... 

We have also observed that the carbon atom of a Fischer carbene is subject to reaction with nucleophiles (Eq. 15.52). 

A variety of other reactions of carbon disulfide with nucleophiles are presented in a review (252). In the last 10 years a number of new 1,1-dithio ligands have been synthesized, and the chemistry of others has been explored in detail. 

Superficially, it might be expected that coordinated acrylic acid would undergo a similar type of hydration reaction with nucleophilic addition taking place at the /3-carbon (the acid is ester-like when coordinated). Experimentally21 hydration is not observed (Scheme 48), but both the 2- and... 

The value of the sulphonate esters in carbohydrate chemistry lies in their ability to undergo cleavage by reaction with nucleophiles in one of two possible ways, (i) cleavage of the S—O bond with regeneration of the hydroxyl group as a result of SN2 attack at the sulphur atom, and (ii) cleavage of the C—O bond as a result of SN2 attack at the carbon atom. 

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