Nucleophilic Aromatic and Vinylic Substitution

NUCLEOPHILIC AROMATIC AND VINYLIC SUBSTITUTION Nucleophilic Aromatic Substitution... 

Catalytic nucleophilic substitution reactions comprise some of the most commonly used catalytic processes in S)mthetic organic chemistry. Substitutions at aromatic and vinylic halides and sulfonates, sho vn generically in Equation 19.1, are commonplace in the preparation of pharmaceutical candidates, have often been used in the s)mtheses of natural products, and have been used many times in the syntheses of sophisticated conjugated organic materials. These metal-catalyzed reactions are typically called cross-coupling reactions. ... 

Nucleophilic vinylic substitutions are closely related to nucleophilic aromatic substitutions, as in both the leaving group leaves from an unsaturated carbon atom. However, the vinylic substitution routes are much more diverse, and disclose more of the details of the reaction. Stereochemical study of the reaction can give information on the lifetime of the intermediate and about the structure of the transition state... 

A listing of alkyne-nucleophile systems whose substitution kinetics have been studied is given in Table 24 for each of these systems. Rate constants and enthalpies and entropies of activation, if available, are tabulated. In order to compare the reactivity of haloalkynes with other organic halides we have also included in Table 24 related rate data for vinylic, aromatic and alkyl halides. 

Nucleophilic substitution reactions of unsaturated compounds containing the G=G double bond are well known and are distinguished by the relative location of the double bond and leaving group. Rappoport has recently reviewed the wide and complex nature of nucleophilic vinylic substitutions. The susceptibility of simple vinyl compounds to nucleophilic attack is low and comparable to unactivated halobenzenes. As is the case with aromatic compounds, however, vinylic substrates may be activated by electron-withdrawing substituents conjugated with the reaction centre. 

The mechanism of these reductions is a bimolecular nucleophilic substitution for the reaction of LAH with most primary and secondary halides [BK5, PCI]. A single-electron transfer (SET) has been proposed in the reduction of sterically hindered primary iodides [AD3, AGl, AWl], although some doubts have been cast [PCI] on this mechanism with bromocyclopropanes [HW2] and aromatic or vinyl halides [Cl], especially in the presence of CeClj [G02]. In this case, some rearrangements may be observed. SET does take place in the reduction of geminal dihalides by LAH [AIM] as well as in the reduction of bromocyclopropanes in the strict absence of molecular oxygen [PNl]. In the presence of oxygen, the C—Br bond of 2,2-diphenyl-l-bromocyclopropanecarboxylic acid is left unchanged [PN1 ]. 

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