Reactions of Heteroatom Nucleophiles

The regioselectivity of palladium-catalyzed aUylic substitutions with heteroatom nucleophiles is often much different from that of reactions with carbon nucleophiles. In general, reactions of oxygen and nitrogen nucleophiles form more branched product than do reactions of carbon nucleophiles, at least as the kinetic product of substitution. For example, reactions of aryloxide nucleophiles with mono-substituted aUylic carbonates catalyzed by palladium complexes of Trost s ligand form more branched than linear product (Equation 20.32). Reactions of geminaUy disubstituted aUylic acetates with aziridines, hydroxylamine and hydrazine derivatives catalyzed by palladium complexes of bisphosphines form the branched prenyl product as the major isomer (Equations 2033a and 20.33b).  

Studies on the origin of die regioselectivity of these reactions revealed that attack by amines occurred at the more-substituted position, but isomerization of the kinetic branched product to the thermodynamic linear product occurred faster than the catalytic process. As a result, the linear isomer was observed as the final reaction product. However, isomerization of the products formed by reactions of aziridines, hydroxylamines, and hydrazone deriviatives was slower than the catalytic substitution process, and these different relative rates allowed isolation of the branched substitution products. The isomerization process presumably occurs by protonation of the amine to form an ammonium salt that undergoes oxidative addition to palladium, as was observed in the initial allyUc substitution processes that involved allylic ammonium salts as electrophile. Thus, addition of a strong, non-nucleophihc base to the reactions of amine nucleophiles allowed isolation of the branched kinetic product.  

Regioselectivity of Reactions Catalyzed by Complexes of Other Metals 

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Selected SN Reactions of Heteroatom Nucleophiles at the Carboxyl Carbon... 

Quite a few substitution reactions of heteroatom nucleophiles at the carboxyl carbon as well as their mechanisms are discussed in introductory organic chemistry courses. The left and the center columns of Table 6.3 summarize these reactions. Accordingly, we will save ourselves a detailed repetition of all these reactions and only consider ester hydrolysis once more. Section 6.4.1 will not only revisit the acidic and basic ester hydrolysis but will go into much more detail. Beyond that, SN reactions of this type will only be discussed using representative examples, namely ... 

In addition, Figures 6.18-6.21 briefly present a handful of other preparatively important SN reactions on the carboxyl carbon. In other words of the many SN reactions of heteroatom nucleophiles at the carboxyl carbon of carboxylic acid (derivative)s we will here discuss those listed in the right column of Table 6.3. 

Table 6.3. Preparatively Important SN Reactions of Heteroatom Nucleophiles at the Carboxyl Carbon of Carboxylic Acids and Their Derivatives...

The last of these special examples of SN reactions of heteroatom nucleophiles at the carboxyl carbon of a carboxylic acid derivative is given in Figure 6.21. There, the free carboxyl group of the aspartic acid derivative A is activated according to the in situ procedure of Figure 6.14 as a mixed carbonic acid/carboxylic acid anhydride B that is then treated with N,0-dimethylhydroxyl amine. This reagent is an N nucleophile, which is thus acylated to give the... 

Fig. 8.11. Tandem reaction consisting of three single reactions mutually transforming heterocumulenes and heteroatom nucleophiles in a one-pot synthesis of an isothiocyanate (1) uncatalyzed addition reaction of heteroatom nucleophile (aniline) + heterocumulene (carbon disulfide) —> carbonic acid derivative (A) (2) heterolysis-initiated /3-elimination of the carbonic acid derivative (D) -> heterocumulene (F = phenylisothiocyanate) + heteroatom nucleophile (thiocar-bonic acid O-ethylester) (3) decomposition of a carbonic acid derivative (D) to a heterocumulene (carbon oxysulfide) and a heteroatom nucleophile (ethanol) via the zwitterion H.

On the Equilibrium Position of Addition Reactions of Heteroatom Nucleophiles to Carbonyl Compounds... 

Reaction of Heteroatom Nucleophiles. Reaction of A -tetraethylthiourea with nitrated -(trifluoromethyl)-diarylsulfonium salt proceeds smoothly without a base to provide a 5 -trifluoromethylated compound (eq 13). Sodium sulfinate readily converts into the corresponding aryl triflone in 81% yield (eq 14). Trivalent phosphorus compounds are also viable electrophiles in the electrophihc trifluoromethylation reaction, providing diethoxytrifluoromethylphosphonate with 70% yield (eq 15). 

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