Nucleophilic species

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

Thiazolium derivatives unsubstituted at the 2-position (35) are potentially interesting precursors of A-4-thiazoline-2-thiones and A-4-thiazoline-2-ones. Compound 35 in basic medium undergoes proton abstraction leading to the very active nucleophilic species 36a and 36b (Scheme 16) (43-46). Special interest has been focused upon the reactivity of 36a and 36b because they are considered as the reactive species of the thiamine action in some biochemical reaction, and as catalysts for several condensation reactions (47-50). 

Primary alcohols do not react with hydrogen halides by way of carbo cation intermediates The nucleophilic species (Br for example) attacks the alkyloxonium ion and pushes off a water molecule from carbon m a bimolecular step This step is rate determining and the mechanism is Sn2... 

The P-halo ketone intermediates formed in the foregoing reactions arise from the capture of carbocationic intermediates by halide of the gegenions. In some cases, solvents such as acetonitrile can act as the competing nucleophilic species. For example, P-amido ketones could be obtained by the acylation of alkenes in acetonitrile (172). 

These reactions proceed via a collision between the reactants, with the nucleophilic species attacking the opposite side of the molecule with respect to the ionic substituent that it liberates. Such a process yields a transition structure in which the ion and neutral reactants are weakly bound. 

An important stage in the synthesis has been reached. It was anticipated that cleavage of the trimethylsilyl enol ether in 18 using the procedure of Binkley and Heathcock18 would regiospecifically furnish the thermodynamic (more substituted) cyclopentanone enolate, a nucleophilic species that could then be alkylated with iodo-diyne 17. To secure what is to become the trans CD ring junction of the steroid nucleus, the diastereoisomer in which the vinyl and methyl substituents have a cis relationship must be formed. In the... 

The hydrogeh atom bound to the amide nitrogen in 15 is rather acidic and it can be easily removed as a proton in the presence of some competent base. Naturally, such an event would afford a delocalized anion, a nucleophilic species, which could attack the proximal epoxide at position 16 in an intramolecular fashion to give the desired azabicyclo[3.2.1]octanol framework. In the event, when a solution of 15 in benzene is treated with sodium hydride at 100 °C, the processes just outlined do in fact take place and intermediate 14 is obtained after hydrolytic cleavage of the trifluoroacetyl group with potassium hydroxide. The formation of azabi-cyclo[3.2.1]octanol 14 in an overall yield of 43% from enone 16 underscores the efficiency of Overman s route to this heavily functionalized bicycle. 

In summary we think that, on a superficial basis, a comparison of the effects of different nucleophilic species added covalently at the (3-nitrogen atom of an arenedi-azonium ion yields results that are almost trivial. Of more interest are unexpected results such as those of Exner and Lakomy for the substituent -N = CHC6H5. A possible explanation for the latter results emerged when the twisted structure of the substituent became known. We emphasize, however, that definitive explanations on the basis of Hammett or related substituent constants are not found very frequently. 

The low efficiency of exchange in water can be explained by postulating that the ion-molecule pair (8.13 in Scheme 8-10) is almost completely trapped by water molecules, i.e., the first intermediate reacts so easily with this more strongly nucleophilic species that the reaction of the second intermediate (8.14) with N2 is not detectable. Therefore, the reaction coordinate diagrams for the dediazoniation in TFE and in water may be visualized as shown in Figure 8-4. 

In view of the successful preparation of so many homochiral sulfoxides via the reaction of nucleophilic species with sulfinate ester 19, it appears likely that the reaction is capable of extension to provide still more examples of potentially useful sulfoxides. 

Finally, an ingenious synthetic sequence by Trost, Cossy and Burks201 includes a unique desulphonylation reaction that involves an electron-transfer process. The synthetic sequence uses 1, l-bis(phenylsulphonyl)cyclopropane as a source of three carbon atoms, since this species is readily alkylated even by weakly nucleophilic species. Given an appropriate structure for the nucleophile, Trost found that desulphonylation with lithium phenanthrenide in an aprotic solvent allowed for an efficient intramolecular trapping of the resultant carbanion (equation 88). This desulphonylation process occurs under very mild conditions and in high yields it will undoubtedly attract further interest. 

In contrast, the reaction mechanism in alkaline solution was shown to occur by nucleophilic attack by the anion of the peracid on the sulphoxide group53. Thus two different mechanisms seem to operate for the oxidation of sulphoxides to sulphones with peracids. At pH < 7 the sulphoxide acts as the nucleophile whilst at pH > 10 the peracid anion is the nucleophilic species. Presumably at intermediate pH values both mechanisms are operable. 

Introduction of the phenylthio group onto the 5-carbon atom of alcohols can have valuable synthetic applications. 5-Phenylthio alcohols can be oxidized to the corresponding 5-sulfoxides and sulfones (with their versatile reactivities) or they can be deprotonated by strong base converting the 5-carbon atom to a nucleophilic species. Conversion of 5-phenylthio alcohols to the corresponding 5-carbonyl compounds can be achieved via halogenation followed by subsequent hydrolysis. In this way an inversion of the reactivity of the 5-carbon atom may be accomplished and it can react as an electron acceptor. 

Peroxomonophosphoric acid (PMPA) oxidizes dimethyl sulphoxide in high yield in water and aqueous ethanol . In neutral solution the reaction mechanism was thought to be very complex but actually occurs by two different mechanisms that are very similar to those for sulphoxide oxidation by peracids in acidic and basic media. In an alkaline medium the mechanism involves nucleophilic attack by a phosphorus-containing species (probably POs ) on the sulphur atom of the sulphoxide, followed by O—O bond scission yielding the sulphone (equation 24). In acidic solution, on the other hand, the sulphoxide is the nucleophilic species as detailed in equation (25). It should be noted however that there is some evidence that these mechanisms are oversimplified since there are other nucleophilic species (such as H2P05 and HPO ") present in aqueous solutions of PMPA over a wide pH range . 

Allylic silanes act as nucleophilic species toward a, (3-unsaturated ketones in the presence of Lewis acids such as TiCl4.130... 

Amongst other N-nucleophilic species, hydroxylamine exhibits some abnormal behavior besides oxime formation (p. 25). Thus it reacts with diphenyl cyclopropenone42 probably by 1,4-addition and subsequent oxidation and/or decarboxylation giving rise to 3,4-diphenyl isoxazolone (328) and desoxybenzoin oxime. With pentyl cyclopropenone48 hydroxylamine undergoes addition followed by normal oxima-tfon after ring fission yielding 2,3-dioximino octane (329). 

---