Nucleophilic Attack by Oxygen

Duthaler, K. Wicker, P. Ackermann, and C. Ganter, Helv. Chim. Acta, 1972, 55, 1809. 

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G. activates the carbonyl group for nucleophilic attack by oxygen lone-pair electrons from the alcohol. 

Examples of nucleophilic attack by oxygen, sulfur and hydride on the 3-position of thietane derivatives are illustrated for thietanes (67) (72BAU505), (68) (75JCS(P1)2513) and (69) (63JA3236) respectively. 

Step 3. Nucleophilic Attack by Oxygen or Nitrogen on Carbonyl Amide... 

One-pot reactions involving successive nucleophilic attack by oxygen and nitrogen on a 1,1-bis-carbon electrophile are used in the synthesis of 2,4-benzoxazepine systems (325) and (326) (72JHC1209,... 

Acetals can be removed under acidic conditions. In this case the two dioxolane groups are cleaved, followed by acid-catalyzed cyclization of the keto-aldehyde to form the A-ring. It is the enol tautomer of the ketone that functions as nucleophile while the aldehyde is activated towards nucleophilic attack by oxygen protonation (51). Cyclization is completed by water elimination to furnish the enone system in 53 (acid-catalyzed aldol-condensation). 

Fig. 8-12. Sites of electrophilic and nucleophilic attacks by oxygen and hydrogen peroxide, respectively, in phenolic and enolic arylpropane units (Gierer and Imsgard, 1977).

Figure 3.39 Formation of anomeric pairs of glycosyl trichloroacetimidates and 2,4-dinitrophenolates. Anhydrous caesium carbonate is also used for trichloroacetimidate formation. In the 2,4-dinitrophenolate epimerisat-ion, nucleophilic attack by oxygen rather than sulfur is proposed since sp -hybridised carbon is a hard electrophile.

The first step in this mechanism is probably the step that most depends on the properties of selenium. Nucleophilic attacks by oxygen nucleophiles on selenium occur considerably more easily than, for example, on sulfur (one could describe a similar mechanism involving an enzymic disulfide, but the first step in such a mechanism would probably be much slower). Consequently, the requirement for selenium in this enzyme may again be related to its unique reactivity characteristics with an oxygen species. 

The dashed line in Figure 3 shows the decrease in the rate constant that would be expected if the entire change in solvation energy that is brought about by two tert-butyl groups (36) were expressed to decrease the rate constant for nucleophilic attack by oxygen anions. This difference is much larger than is needed to explain the observed decreases in rate for the most basic anions. 

As amply indicated in Part V, the Wacker oxidation involves (i) alkene 77-complexation with Pd, (ii) nucleophilic attack by oxygen nucleophiles, such as H2O, and (iii) jS-dehydropaUada-tion (Schemes 2 and 3 in Sect. V.l). In addition to these three critical steps, oxidation of Pd(0) to Pd(II) is necessary for recycling Pd complexes as catalysts, hi this reaction, C—H bond participation occurs in the /3-eUmiiiation or 1,2-elimination of the oxypaUadated intermediate. 

Synthesis.— This section is again divided into routes requiring oxidation of alcohols, nucleophilic attack by oxygen at a saturated centre or by trapping of an intermediate consequent upon electrophilic attack at an unsaturated centre, and various cycloaddition reactions. 

Nucleophilic attack by oxygen on the methylene group, resulting in departure of the weakly basic leaving group, forms a five-membered ring (Section 9.2). Acid-catalyzed hydrolysis of the imine cleaves the protein (Section 17.10). 

Under conditions of acid catalysis, it is the enol tautomer of the aldehyde or ketone that functions as the nucleophile. The carbonyl group is activated toward nucleophilic attack by oxygen protonation. 

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