Ammonium nucleophilic addition

The enantio-determining step of nucleophilic additions to a-bromo-a,y -unsaturated ketones is mechanistically similar to those of nucleophilic epoxidations of enones, and asymmetry has also been induced in these processes using chiral phase-transfer catalysts [20]. The addition of the enolate of benzyl a-cyanoacetate to the enone 31, catalysed by the chiral ammonium salt 32, was highly diastereoselective and gave the cyclopropane 33 in 83% ee (Scheme 12). Good enantiomeric excesses have also been observed in reactions involving the anions of nitromethane and an a-cyanosulfone [20]. 

One simple way for arriving at a photoinduced Markovnikov-type amination of olefins is illustrated in Scheme 3.15, for the case of o-alkenylphenols (e.g., 24). Here, an ammonium salt of the o-alkenylphenolate anion (25) is prepared and irradiated this causes proton transfer within the ion pair (from the amine to the olefin), and the resulting zwitterion undergoes nucleophilic addition of the amine at the benzylic cation center. The addition is selective for N- rather than O-nucleophiles, as shown in the case of ethanolamine [34]. 

This nucleophilic addition of hydrogen fluoride can be effected by ammonium fluoride, potassium fluoride, or tetraethyl- or tetrabutylammonium fluoridc in formamide or chloroform.For example, formation of 1,1,1,2,3,3,3-heptafluoropropane. ... 

The nucleophilic character ofdialkyl sulfides is illustrated by their nucleophilic addition reaction with alkyl halides to form the corresponding sulfonium salts (35) (Scheme 13). Asymmetric sulfonium salts (36) have a tetrahedral configuration therefore, like the analogous chiral saturated carbon compounds, they can be resolved into optical enantiomers (see Chapter 6, p. 81). They are, however, generally less optically stable than sulfoxides, but in sulfonium salts the unshared electron pair can hold its configuration at ordinary temperatures, unlike nitrogen in quaternary ammonium salts, enabling their resolution to be achieved. 

Nucleophilic Addition of Ammonium Ketene Enolate to C O or C N Bonds... 

Treatment of cyclopropyl sulfides bearing a hydroxy group in the side chain with ceric ammonium nitrate (CAN) in methanol gives five- and six-membered cyclic ethers.In this reaction, the formation of cyclic ethers is understood by assuming a single electron transfer mechanism, which involves ring opening of the cation intermediate followed by intramolecular nucleophilic addition. 

Nucleophilic attack at carbon atoms is quite common and usually results in opening of the heterocycle. Among the most typical types of substrate, one finds 1,2,3-oxathiazines. For example, in the nucleophilic addition of tetrabutyl-ammonium fluoride (TBAF) to 1,2,3-oxathiazine 103, the tetrabutylammonium alkoxide intermediate 104 reacts intramolecularly to give 3-aminotetrahydrofuran 105 <20050BC603>. Substrate 103 undergoes similar nucleophilic additions with morpholine and phenylthiolate to afford derivatives 106 and 107 (Scheme 9). 

This reaction was also studied with a more complicated nitro ketoester starting material [10]. hi this example, the nucleophilic addition occurs intramolecularly to form a 15-membered macrocycle. Zinc/ammonium chloride reduction to form the hydroxyindole 16 followed by cyclization provided a better yield of 17 (40% over both steps) than the direct tin dichloride reduction of 15 to macrocycle 17 (10%). 

Yasuda et al. have recently reported that irradiation of o-alkenylphenols and naphthols in the presence of primary or secondary amines results in Markovnikov addition of the amine. For example, irradiation of the alkenylphenol 12 with methyl-amine affords the adduct 13 (Scheme 4), The initial step in these reactions is proton transfer from the acidic phenol singlet state to the amine, which leads to the formation of the singlet phenolate anion and ammonium ion. Proton transfer from the ammonium ion to the phenolate anion yields a zwitterion, which undergoes nucleophilic addition of the amine. Thus the amine serves as a base in the initial step of this reaction and then as a nucleophile. 

The rates of nucleophilic addition to carbonyl groups that you met in Chapter 6 depend on the basicity of nucleophiles. As nitrogen bases are much stronger than oxygen bases (or, if you prefer, ammonium ions are much weaker acids than H3O ), amines are also much better nucleophiles than water or alcohols. This is dramatically illustrated in an amide synthesis from aniline and acetic anhydride in aqueous solution. 

In 1965 researchers at the American University of Beirut observed that combining benzofurazan oxides with morpholine-cyclohexene in methanol afforded quinoxaline-1,4-dioxide in 48% yield. There is some debate in the literature as to the exact mechanism of the Beirut reaction. In the case of benzofurazan oxides reacting with an enamine, the following mechanism is generally accepted in the literature. The first step is nucleophilic addition of the enamine to the electrophilic benzofurazan oxide to form the ammonium zwitterion. Ring closure occurs via condensation of... 

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