Ambident nucleophilic species

However, when it comes to thiopyrones an enormous range of substituents is known and almost any of the methods of ring synthesis outlined above may be used. It is especially easy to set up ambident nucleophilic species such as (143) which may be S-alkylated to (144). Thermolysis isomerizes such compounds to the 4,6-bis(alkylthio) analogues the rearrangement has been thoroughly investigated (67JOC3140). 

The equation does not take into account such pertubation factors as steric effects, solvent effects, and ion-pair formation. These factors, however, may be neglected when experiments are carried out in the same solvent at the same temperature and concentration for an homogeneous set of substrates. So, for a given ambident nucleophile the rate ratio kj/kj will depend on A and B, which vary with (a) the attacked electrophilic center, (b) the solvent, and (c) the counterpart cationic species of the anion. The important point in this kind of study is to change only one parameter at a time. This simple rule has not always been followed, and little systematic work has been done in this field (12) stiH widely open after the discovery of the role played by single electron transfer mechanism in ambident reactivity (1689). 

Ambident reactivity of the same nucleophilic species toward different nitrosation electrophilic centers. 

Kf., while not quantified experimentally, was recently introduced by Kirby and coworkers on the basis of product formation from O-attack at electrophilic P and C centers, as well as MO calculations incorporating the novel species, ammonia oxide, NH3+-0 . In common with other ambident nucleophiles, factors such as electronic, steric, kinetic and thermodynamic effects will determine actual extant pathways in a given system. Af-substituted hydroxylamines (see Scheme 1) can in principle partake of the equilibria shown in Scheme 2. Again, actual outcomes will be influenced by the aforementioned criteria. 

Regiochemical control of the addition of 1-phenylselenoallyllithium to cyclopentenone has been achieved - in a manner similar to that mentioned alrove. In THF alone the C-1 adducts resulting from the attack of the ambident nucleophile at its a- and y-sites prevail (Scheme 127, whereas the C-3 adducts resulting from the almost exclusive reaction of the a-selenoallyllithium at its a-site are pro-duced - if the reaction is performed instead in the presence of HMPA (Scheme 127, b). Therefore, this solvent mixture allows the simultaneous control of the sites of attack of these two ambident species. 

Ally lie sources are ambident nucleophiles (Sections 5.4 and 9.4) and can therefore attack an electrophile at either of two sites. Since proton transfer is commonly reversible and rapid, an equilibrium mixture is quickly achieved. When the source is anionic, the protonation occurs most rapidly on the heteroatom (hard-hard, path p.t.) but can also occur on carbon. Equilibration to the more stable product occurs by proton transfer (Section 7.3.8, tautomerization). A AH calculation (Section 2.5) will verify that the carbon-protonated species is the more stable product. 

In its reactions, the indolyl anion behaves as an ambident nucleophile the ratio of N- to P-substitution with electrophiles depends on the associated metal, the polarity of the solvent, and the nature of the electrophile. Generally, the more ionic sodio and potassio derivatives tend to react at nitrogen, whereas mag-nesio derivatives have a greater tendency to react at C-3 (see also 20.1.1.4), however, reaction of indolyl Grignards in HMPA leads to more attack at nitrogen. Complimentarily, more reactive electrophiles show a greater tendency to react at nitrogen than less electrophilic species. 

The common method involves deprotonation of a thiocarbonyl compound and reaction of the intermediate enethiolate with an allyl halide (Scheme 9.8). This actually relies on two noticeable features of the sulfur series. (1) The proton located a to a thiocarbonyl group is much more acidic, by 7-10 pKa units, than the one of a carbonyl moiety [39, 41]. This may be related to the strong ability of the sulfur atom (polarizability) to stabilize the negative charge of the enethiolate. Presently, the preferred conditions involve LDA as a base for optimum deprotonation [42-45]. (2) The resulting anionic species are soft ambident nucleophiles. The... 

In the case of thiocyanogen chloride and thiocyanogen, the formal electrophile is N=C—The presumed intermediate is a sulfur-bridged species. The thiocyanate anion is an ambident nucleophile and both carbon-sulfur and carbon-nitrogen bond formation can be observed, depending upon the solvent (see Entry 9, Scheme 4.4). 

One can draw a resonance structure for the 2,6-di-tert-butylphenoxide ion which shows the carbon para to the oxygen as a nucleophilic center that is, the species is an ambident nucleophile. 

This section is organized according to the electrophilic center presented to the nucleophilic nitrogen of the active species. This organization allow s a consistent treatment of the reactivity. However, a small drawback arises when ambident electrophilic centers are considered, and these cases are treated as if the more reactive center were known, which is not always the case. 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

A nice example of the solvent-dependent dual reactivity of an electrophilic crypto-cationic species has been given by Hiinig et al. [663]. Ambident electrophilic a-enones react with nucleophiles such as the anion of the benzaldehyde O-(trimethylsilyl)-cyanohydrin (Nu ) in diethyl ether exclusively by 1,4-addition. In tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME), the 1,2-adduct is formed predominantly on the addition of HMPT or [12]crown-4 it is formed exclusively cf. Eq. (5-133). 

Each resonance form contributes to the characteristics of the enolate ion and thus to the chemistry of carbonyl compounds. The resonance hybrid possesses partial negative charges on both carbon and oxygen as a result, it is nucleophilic and may attack electrophiles at either position. A species that can react at two different sites to give two different products is called ambident ( two fanged from ambi, Latin, both dens, Latin, tooth). The enolate ion is thus an ambident anion. Its carbon atom is normally the site of reaction, undergoing... 

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