Attack of nucleophile

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

A direct attack of nucleophiles on the sulfur atom of the sulfone or sulfoxide group in acyclic or large-ring sulfones and sulfoxides is rather rare, or unknown, excluding metal hydride reductions and/or reductive deoxygenations. The situation is completely different in the three-membered ring systems. 

The mechanism of this reaction is not known. However, some evidence18-98-143 suggests the mechanism (equation 39) with the zwitterion 101 as a key intermediate. This is in accord with the known favored attack of nucleophiles at the sulfur atom of sulfenes143. 

There has been a plethora of recent hterature regarding the synthetic manipulations of the 2(lH)-pyrazinone skeleton. Even though the addition-elimination reactions at the C-3 position to decorate the pyrazinone scaffold are well documented [24], the versatihty of such approaches can be found somewhat limited. Selective attack of nucleophiles on the chloroimine group of the pyrazinone system can generate 3-alkoxy- and 3-amino-pyrazinones (Scheme 9) [27,28]. The 3-CN group was introduced via a Rosemund-von Braun reaction with copper(I)cyanide under harsh conditions (heating in NMP at 150 °C) [27] (Scheme 9). 

The LUMO of cyclohexanone 3 is an out-of-phase combination of the carbonyl It orbital with the orbital (5 in Fig. 4). The out-of-phase enviromnent disfavors attack from the face of the bonds (motif ii in Fig. 1). This leads to the axial attack of nucleophiles. The observed selectivities are in agreement with the orbital... 

In these a-phosphorylated dithioesters, the electron-withdrawing effect of the phosphono group, which strongly increases the electrophilic character of the thiocarbonyl group, makes the latter more prone to the thiophilic attack of nucleophiles and stabilizes the resulting carbanion. The main reactions of 1 with nucleophiles are summarized in Scheme 2. 

Attack of nucleophile (e.g., water or hydroxyl ion) on an electrophile (e.g., carbon or phosphorus), resulting in bond cleavage and displacement of file leaving group... 

The LU MO of ethyl chloride (trans form) extends in the region of the a carbon to the direction opposite the side of the chlorine atom and also in the region of the hydrogen atom trans coplanar to the chlorine atom 124>. The former is responsible for the attack of nucleophile in Sn2 reactions, and the latter for the attack in E 2 reactions. 

This concentration of charge might be expected to shield the ring carbon atoms from the attack of nucleophilic reagents and, by contrast, to promote attack by cations, X , or electron-deficient species, i.e. by electrophilic reagents this is indeed found to be the case. 

In much the same way it should be possible to discriminate between attack by anionic and non-ionic nucleophiles. Micelles, regardless of charge, generally speed attack by non-ionic nucleophiles, but the enhancements are typically small, whereas large inhibition or enhancement is observed for attack of nucleophilic anions, depending upon micellar charge. 

Data are for 25 °C and 60% dioxan as solvent (Kice and Liu, 1979) b Rate constants are total rate of attack of nucleophile on PhS(0)SPh. Preference for site of attack (or S=0) shown in parentheses where known... 

C9 and Cl 1 are both electrophilic. The cyclic magnesium compound is nucleophilic at Cl and C8, and allylically at C7 and C2. The first step, then is nucleophilic attack of nucleophilic C7 on electrophilic C9 to give an alkoxide. Then when CO2 is added, the nucleophilic C8 carbanion attacks the electrophilic Cl 1. 

Both C2 and C3 are (3 to an OH group, and C3 is also (3 to a carbonyl. Thus C3 is subject to both pushing and pulling, but C2 is subject only to pushing. The first step then is likely attack of nucleophilic C2 on electrophilic C11. Then the C3 carbocation is trapped by 012. 

Co-ordination of an alkene to an electronegative metal (often it may carry a positive charge) activates the alkene toward attack of nucleophiles. After the nucleophilic attack the alkene complex has been converted into a c-bonded alkyl complex with the nucleophile at the (3-position. With respect to the alkene (in the "organic" terminology) the alkene has undergone anti addition of M and the nucleophile Nu, see Figure 2.25. 

A development of the last two decades is the use of Wacker activation for intramolecular attack of nucleophiles to alkenes in the synthesis of organic molecules [9], In most examples, the nucleophilic attack is intramolecular, as the rates of intermolecular reactions are very low. The reaction has been applied in a large variety of organic syntheses and is usually referred to as Wacker (type) activation of alkene (or alkynes). If oxygen is the nucleophile, it is called oxypalladation [10], Figure 15.4 shows an example. During these reactions the palladium catalyst is often also a good isomerisation catalyst, which leads to the formation of several isomers. 

PtCl(Ph3P)2CO + ROH PtCl(Ph3P)2C(0)0R Rare attack of nucleophile on carbon rather than on metal d... 

Ab initio calculations carried out by Tanaka and Kanemasa conclude that, under Lewis acid-catalyzed conditions, the formation of eudo-cycloadducts is preferred and that the attack of nucleophilic nitrone oxygen should become more favored to occur at the p-position of the enal rendering 3,4-cycloadducts [39]. In the iridium... 

As a result, the reactivity of these metal-NHC compounds is also unique. They prove to be rather resistant towards attack of nucleophiles or electrophiles at the divalent carbon atom. Additionally, theoretical calculations and experimental investigations agree that the ligand dissociation energy for an NHC is higher than for a phosphine. 

The attack of nucleophiles on unsaturated ligands or functional groups bonded to metallic centers, exemplified in Scheme 9 (reaction of metallic carbenes with phosphines or pyridines) or in Scheme 15 (Wittig reaction) can be extended to a wide variety of reagents. Two main groups of reactions can be considered (1) those in which the nucleophile is an ylide and (2) those in which the nucleophile is a phosphine (and less commonly other nucleophiles). Usually these reactions give metallated ylides (type III), that is, species in which the ylide substituents are metallic centers. 

Epoxides, like cyclic halonium ions, undergo ring opening through rearside attack of nucleophiles (see Section 6.3.2). Two mechanisms are shown, for both basic and acidic conditions. Under acidic conditions, protonation of the epoxide oxygen occurs first. The epoxidation-nucleophilic attack sequence also adds substituents to the double bond in an anti sense. 

Acid-catalyzed intramolecular attack of nucleophilic hydroperoxide function on an oxirane ring results in formation of 3-(l-hydroxyalkyl)endoperoxides. For example, epoxidation of unsaturated hydroperoxide 320 affords oxirane-hydroperoxide 321 (66%), which through acid-catalyzed regioselective cyclization gives 1,2-dioxolane 322 (70%) (Scheme 79) . This type of reaction is applicable also to a more complex epoxide-hydroperoxide such as 323, which cyclizes to polyfunctionalized 5-membered cyclic... 

Attempts to rationalize the regioselectivity of attack of nucleophiles on the aryl rings of nitrenium ions in terms of calculated properties of the ions (LUMO coefficients, localization energies, etc.) have been moderately successful. An adequate explanation of electrophilic reactivity of nitrenium ions at N with certain nucleophiles such as glutathione, C-8 of d-G, and other carbon nucleophiles has not yet appeared. ... 

The arene oxide valence tautomer of oxepins in principle should undergo nucleophilic substitution reactions (Sn2) which are characteristic of simple epoxides. In reality oxepin-benzene oxide (7) is resistant to attack by hard nucleophiles such as OH-, H20, NH2- and RNH2. Attempts to obtain quantitative data on the relative rates of attack of nucleophiles on (7) in aqueous solution hqye been thwarted by competition from the dominant aromatization reaction. 

In another cyclization procedure for the 1,5-benzodiazodne system, the nitriles (296) are converted to the aminodihydrodiazocines (297) (79CPB2589). Attack of nucleophiles on (297) occurs at the N-5—C-6 bond to give the 3,4,5,6-tetrahydrodiazodnes (298) with NaBH4 and the jS-aminoethylquinazolines (301) on hydrolysis. The diazocines (297) behave as typical amidines. Oxidation leads to the amidoximes (300) which on hydrolysis are converted to 2,1-benzisoxazoles (302), and reaction with diketene leads to the fused pyrimidinones (299 and l-methyl-3-one isomer) (79CPB2927). 

The preparation of thiols by S ,2 attack of nucleophilic HS on an alkyl halide gives poor yields because the mercaptan loses a proton to form an anion, RS, which reacts with a second molecule of alkyl halide to form a thioether. 

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