Allylic halides 3-heteroatom-substituted

Nucleophilic Substitution on Alkyl Halides by Heteroatoms. A number of more or less activated alkyl halides, such as benzyl halides and allyl halides, undergo substitution reactions mediated by AgBp4 in the presence of a heteroatom nucleophile. For example, treatment of pentamethylcyclopentadienyl bromide with AgBp4 in the presence of a nucleophile gives the corresponding substituted product (eq 2). Thiols, amines, and alcohols have been used as nucleophiles. ... 

Cathodic substitution stands for C,C bond or C, heteroatom bond formation with cathodically generated anions. The question of regioselectivity is encountered in the reaction of such anions with allyl halides (path a) or in the reaction of allyl anions generated in an ECE process from allyl halides (path b). Cathodic reductive silylation of an allyl halide proceeds regioselectively at the less substituted position (Fig. 15) [91]. From the reduction potentials of the halides it is proposed that the reaction follows path b. 

Another type of substitution reaction is increasing in popularity—the use of an allylic substrate, such as an allyl acetate where the nucleophile is introduced with stereochemical control in the presence of a palladium catalyst and a chiral ligand. Reactions where a chiral anion, be it derived from a chiral heteroatom group, such as a sulfoxide, or an auxiliary, such as Evans s oxazolidinones, are not included in this chapter because the alkyl halide is usually relatively simple and the stereochemical selectivity is derived from the system itself. 

Enantiosdective allyic substitution processes have been developed over the course of 30 years. Initial observations of the reactions of nucleophiles with paUadium-allyl complexes led to the observation of catalytic substitutions of aUylic ethers and esters, and then catalytic enantioselective aUylic substitutions. The use of catalysts based on ottier metals has led to reactions that occur with complementary regiochemistry. Moreover, flie scope of the reactions has expanded to include heteroatom and unstabilized carbon nucleophiles. Suitable electrophiles for these reactions indude allyhc esters of various types, allyhc ethers, aUylic alcohols, and aUylic halides. Enantioselective reactions can be conducted with monoesters or by selection for deavage of one of two equivalent esters. The mechanism of these reactions occurs by initial oxidative addition to form a metal-aUyl complex. The second step involves nudeophilic attadc on ttie aUyl ligand for reaction of "soft" nudeophiles or inner-sphere reductive eUmination for reactions of "hard" nudeophiles. The external nudeophilic attack typicaUy occurs by reaction of the nudeophile with a cationic aUyl complex at the face opposite to that to which Uie metal is bound. Exceptions indude reactions of certain molybdenum-aUyl complexes. Dissociation of product then regenerates the starting catalyst. Because of the diversity of the classes of these reactions, aUylic substitution—in particular asymmetric aUylic substitution—has been used to prepare a wide variety of natural products. 

Activation of C-X Bonds. The activation of C-X single bonds toward nucleophilic substitution is also mediated by the Lewis acidic character of ZnCl2. Benzylic (eq 33), allylic (eq 34), propargylic, and tertiary halides (eq 35) undergo substitution with mild carbon and heteroatom nucleophiles. 

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