Alkylation of nucleophiles

Fig. 2.4. Generation and O-alkylation of nucleophilic acyl complexes from metallates and acyl halides [101].

Based on these studies, it has been suggested that alkylation of nucleophilic sites, including SH-containing enzymes, is the underlying biochemical lesion responsible... 

Interactions with Alkylation of nucleophilic sites Results in V J... 

The high reactivity of acronycine epoxide f6n led us to speculate that this compound should be the active metabolite of acronycine in vivo and that it should be responsible for the alkylation of nucleophilic targets within the tumor cell (68). This hypothesis was in good agreement with the mode of action previously established (76) for the insecticidal chromenes precocenes I (62) and II (63 ). whose structures share a dimethylbenzopyran unit in common with acronycine (i). 

The pyran double bond plays a crucial role in the insecticidal activity of precocenes, since the corresponding epoxides, formed in situ through cytochrome P 450 mediated oxidation, are the active metabolites of these compounds (76-78). These extremely reactive epoxides are responsible for the alkylation of nucleophiles present in biological matrices and ultimately... 

The gem-difluoroalkenylphosphonate (183) has been synthesised by reaction of lithiated diethyl methylphosphonate with a-trifluoromethylstyrene. 1-Substituted 5-trifluoromethyliniidazole-4-phosphonates (185) have been prepared in moderate yield by the reaction of isocyanomethylphosphonate carbanions with trifluoroacetimidoyl chlorides (184). Diphosphono-alkylation of nucleophiles has been achieved in one pot by sequential treatment of phosphonate carbanions with alkyl dichlorophosphates and the conjugate acid of the appropriate nucleophile (Scheme 23). ... 

Suggest Starting materials and reaction conditions for obtaining each of the following compounds by a procedure involving alkylation of nucleophilic carbon ... 

The second most common method to prepare metal-alkyl complexes is the alkylation of nucleophilic metal complexes. Like protonations, these alkylations are formal oxidative additions, and are discussed in that context in Chapter 7, which covers oxidative addition of polar reagents. The reaction between an anionic metal-alkyl complex and an alkyl halide is most common (Equations 3.6 and 3.7), but examples of such reactions between neutral metal-alkyl complexes and alkyl halides are also known (Equation 3.8). ... 

Chapter 1. Alkylation of Nucleophilic Carbon. Enolates and Enamines... 

Because an alkyl group is added to the original alkyne molecule, this type of reaction is called an alkylation reaction. We limit our discussion in this chapter to reactions of acetylide anions with methyl and primary haloalkanes. We will discuss the scope and limitation of this type of nucleophilic substitution in more detail in Chapter 7. For reasons we will discuss there, alkylation of nucleophilic acetylide anions is practical only for methyl and primary halides. While this alkylation reaction can be used with limited success with secondary haloalkanes, it fails altogether for tertiary haloalkanes. 

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