Nucleophilic addition process

Chemical groups that specifically react with carboxylic acids are limited in variety. In aqueous solutions, the carboxylate functionality displays rather low nucleophilicity. For this reason, it is unreactive with the great majority of bioconjugate reagents which couple through a nucleophilic addition process. 

A number of structural and mechanistic studies of related nucleophilic addition processes deserve close scrutiny since they provide relevant parallels that are useful in the analysis of the Mukaiyama aldol addition reaction [43, 44]. 

For this reaction, reactant and product configurations are depicted by III and IV, respectively. Here again, we see that reaction comes about by a singleelectron shift. The product configuration has two spin-paired electrons on O and C that can form a bond once that electron shift has occurred. So we see that the difference between a nucleophilic addition process and SET lies not in the number of electrons that are shifted but in whether two coupled electrons in close proximity are generated following the electron shift. This statement is the essence of the polar-SET competition. In a SET pathway D, A reacts to form D+,A , while in a polar process such as that in equation 5,... 

Precisely the nucleophilic addition process may be regarded to accomplish in three important sequential steps, namely ... 

It has been discussed in Section 9.02.5.7.1 that upon reaction with simple nucleophiles, 1,2,4-triazines generally participate in monoaddition reactions at C-5. However, the nucleophilic addition process is not complete at this stage, and a subsequent addition of a nucleophile may occur, resulting in the formation of diadducts at C-5 and C-6. This mode of nucleophilic diaddition usually requires as prerequisite that the 1,2,4-triazine ring is strongly activated either... 

It may be further added that Brown " employed peroxide as an initiator in the reaction of MA with thiolacetic acid as mentioned earlier. Its necessity was not explored and may be unnecessary in that particular case. Dmuchovsky and coworkers have also shown that added radical inhibitor has no effect on the rate of thiol disappearance.Since the peroxide-catalyzed addition of thiol to olefin is known, only its contribution in relatively facile nucleophilic addition processes is questioned. 

The transformations in eqs 1 and 2 ultimately produce palla-dium(0), whilepaUadium(II) is required to activate alkenes (eq 1). Thus, if such a process is to be run using catalytic amounts of the noble metal, a way to rapidly regenerate palladium(II) in the presence of both substrate and product is required. Often this reoxidation step is problematic in palladium(II)-catalyzed nucleophilic addition processes, and reaction conditions have to be tailored to fit a particular type of transformation. A number of very useful catalytic processes, supplementing the processes that employ stoichiometric amounts of the metal, have been developed. " ... 

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