Nitrogen-centered Nucleophiles

As the cinchona alkaloids contain a nucleophilic nitrogen center, they can be alkylated at this position. Thus, cinchonidine reacts with benzyl chlorides to form quaternary salts, e.g., 9 and 108, which are useful as chiral phase-transfer catalysts (see Section D.1.5.2.4. for enantioselec-tive additions to azaenolates, and D.4.1. for the oxidation of enolates). Further modification by catalytic reduction of the double bond (hydrogen/platinum) leads to the corresponding dihydrocinchonidine derivatives. 

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. 

With alkali cyanides, a reaction via a SN2-mechanism takes place the alkyl halide is attacked by cyanide with the more nucleophilic carbon center rather than the nitrogen center, and the alkylnitrile is formed. In contrast, with silver cyanide the reaction proceeds by a SnI-mechanism, and an isonitrile is formed, since the carbenium intermediate reacts preferentially with the more electronegative center of the cyanide—i.e. the nitrogen (Kornblum s rule, HSAB concept). ... 

The Michael adclidon of a nitrogen-centered nucleophile to nitroalkenes affords compounds that may serve as precursors of vicinal chamines, since the nitro group can be reduced to an amino function by reduction The very convenient method for the preparation of 1,2-chamines is developed by the adchdon of O-ethyihydroxylamines to nitroalkenes followed by redncdon with H-, in the presence of PckC fEq 4 24 ... 

Despite these significant results in azide additions, only limited success has been obtained in enantioselective addition of other sp2-hybridized nitrogen-centered nucleophiles to meso-epoxides. Bartoli et al. demonstrated that aniline was a... 

Two recent reports described addition of nitrogen-centered nucleophiles in usefully protected fonn. Jacobsen reported that N-Boc-protected sulfonamides undergo poorly selective (salen) Co-catalyzed addition to racemic epoxides. However, by performing a one-pot, indirect kinetic resolution with water first (HKR, vide infra, Table 7.1) and then sulfonamide, it was possible to obtain highly enantiomer-ically enriched addition products (Scheme 7.39) [71]. These products were transformed into enantioenriched terminal aziridines in straightforward manner. 

Although several interesting nitrogen-centered nucleophiles have been developed with ARO reactions of epoxides (vide supra), kinetic resolutions with such reagents are unlikely to be of practical value for the recovery of enantioenriched terminal epoxides. This is due to the fact that these nucleophiles are too valuable to be discarded in a by-product of the resolution, are generally not atom-economical, and, particularly in the case of azide, may represent safety hazards. 

Diastereoselective conjugate addition of oxygen and nitrogen- centered nucleophiles to nitroalke-nes derived from (+)-camphoisulfonic acid and ozonolysis give a-hydroxy and a-amino thiol acid derivatives (Eq. 4.39). In all cases, the (/ )-diasteromer is formed as the major component.49... 

In preparation for E ring closure, the appended nitrogen center required deacylation for sufficient nucleophilicity. Of concern were the... 

Amino groups are well established as intramolecular donors for silicon centers [1]. Due to the enhanced nucleophilicity of hydrazines the intramolecular coordination ability of the terminal nitrogen center in the 2-(trimethylhydrazino)phenyl substituent (PTMH) is expected to be stronger than in the 2-(dimethyl-aminomethyl)phenyl substituent (DMBA). 

A fundamental route for the preparation of simple tetraalkylphosphonium salts is the reaction of a tertiary phosphine with a haloalkane or other substrate upon which a simple nucleophilic substitution reaction can occur. (In comparing phosphorus nucleophiles with the corresponding nitrogen-centered nucleophiles, it must be remembered that the phosphorus is significantly more nucleophilic than is the nitrogen. For example, while triphenylamine is devoid of nucleophilic character in reaction with ordinary haloalkanes, triphenylphosphine exhibits high reactivity.) Reactivity of the phosphorus in such nucleophilic substitution reactions, as with other types of nucleophiles, decreases with increasing substitution about the electrophilic site of the substrate. 

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