Protein targeting with SAF(er) electrophiles

This lesson explains the definition, classification, and characteristic features of an electrophile that are key features of nucleophilic substitution reactions. An analysis of their charge and orbital picture helps understand their reactivity for seeking electrons. Electrophiles can be classified into positive and neutral species. Other classes include free radicals and polar functional groups.
While a positive electrophile, like a proton, reacts due to its vacant, low-energy 1s orbital, the...

Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the...

If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...

Radicals adjacent to electron‐withdrawing groups are called electrophilic radicals. These radicals readily react with nucleophilic alkenes. For example, the malonate radical, in which the radical center is flanked by two electron‐withdrawing groups, reacts readily with butyl vinyl ether, which consists of an electron‐donating oxygen substituent. The reaction between electrophilic malonate radical and nucleophilic vinyl ether is favored because the radical has a...

Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired chemical reactions. These compounds can selectively bind to particular functional groups and advance chemoselective reactions in polyfunctional systems (Figure 1). After the functional group has served its purpose, it is removed by reacting it with specific compounds.

Radicals adjacent to electron-donating groups are called nucleophilic radicals. These radicals readily react with electrophilic alkenes. The SOMO–LUMO interactions are the driving force for the reaction, where the high-energy SOMO of the electron-rich, nucleophilic radicals interacts with the low-energy LUMO of the electron-deficient, electrophilic alkenes. Such SOMO–LUMO interactions are the basis of reactive radical traps, affecting the selectivity in radical reactions. For...