A Different Mechanism for Alkyl Halide Elimination The

A DIFFERENT MECHANISM FOR ALKYL HALIDE ELIMINATION THE El MECHANISM... 

A Different Mechanism for Alkyl Halide Elimination The El Mechanism... 

Reductive eliminations to form carbon-heteroatom bonds occur by several mechanisms. As would be expected from microscopic reversibility, these mechanisms parallel those for the oxidative addition of carbon-heteroatom bonds. Recall that oxidative additions to form Pt(IV) alkyl halide complexes and oxidative additions to form Pd(II) alkyl and aryl halide complexes occur by different pathways. The former occurs by a stepwise mechanism involving charged intermediates, and the latter occurs by concerted pathways. 

We take up the aryl halides in a separate chapter because they differ so much from the alkyl halides in their preparation and properties. Aryl halides as a class are comparatively unreactive toward the nucleophilic substitution reactions so characteristic of the alkyl halides. The presence of certain other groups on the aromatic ring, however, greatly increases the reactivity of aryl halides in the absence of such groups, reaction can still be brought about by very basic reagents or high temperatures. We shall find that nucleophilic aromatic substitution can follow two very different paths the bimolecular displacement mechanism for activated aryl halides and the elimination-addition mechanismy which involves the remarkable intermediate called benzyne. 

There is a strong similarity between the mechanism shown in Figure 5.12 and the one shown for alcohol dehydration in Figure 5.6. Indeed, we can describe the acid-catalyzed dehydration of alcohols as an El elimination of their conjugate acids. The main difference between the dehydration of 2-methyl-2-butanol and the dehydrohalogenation of 2-bromo-2-methylbutane is the source of the carbocation. When the alcohol is the substrate, it is the corresponding alkyloxonium ion that dissociates to form the carbocation. The alkyl halide ionizes directly to the carbocation. 

The general reaction mechanism has been shown to involve typical steps for cross-coupling [98, 113]. Oxidative addition of an aryl halide generates a Pd(II) species that undergoes transmetalation to form a Pd(II)-thiolate. C-S reductive elimination provides the aryl sulfide and regenerates the Pd(0) catalyst. More recently, Hartwig reported a detailed mechanistic analysis of the Pd/Josiphos system derived from different Pd precursors. The dominant Pd species were found to be off the catalytic cycle, which accounted for differences in rates between stoichiometric and catalytic reactions [114]. Thioketones are also effective thiolate nucleophiles for C-S bond formation. The reaction involves tandem Pd-catalyzed thioenolate alkylation, followed by 5-arylation (8) [102]. Presumably, the arylation process proceeds by a similar mechanism to related Pd-catalyzed transformations. 

The biggest challenge with this material is learning how to sort out two different reactions that follow four different mechanisms. Will a particular alkyl halide undergo substitution or elimination with a given reagent, and by which of the four possible mechanisms To answer this question, we conclude Chapter 8 with a summary that allows you to predict which reaction and mechanism are likely for a given substrate. 

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