Alkyl halides vinyl substitutions

Unlike elimination and nucleophilic substitution reactions foimation of oigano lithium compounds does not require that the halogen be bonded to sp hybndized carbon Compounds such as vinyl halides and aiyl halides m which the halogen is bonded to sp hybndized carbon react m the same way as alkyl halides but at somewhat slowei rates... 

Substitution at the Carbon—Chlorine Bond. Vinyl chloride is generally considered inert to nucleophilic replacement compared to other alkyl halides. However, the chlorine atom can be exchanged under nucleophilic conditions in the presence of palladium [7440-05-3] Pd, and certain other metal chlorides and salts. Vinyl alcoholates, esters, and ethers can be readily produced from these reactions. 

Nucleophilic substitution by cyanide ion (Sections 8.1, 8.13) Cyanide ion is a good nucleophile and reacts with alkyl halides to give nitriles. The reaction is of the S m2 type and is limited to primary and secondary alkyl halides. Tertiary alkyl halides undergo elimination aryl and vinyl halides do not react. 

Coupling of certain lithiated reagents with aryl and vinyl halides is also possible.82 These reactions probably proceeds by a fast halogen-lithium exchange, generating the alkyl halide, which then undergoes substitution. This reaction has been applied to P-lithiobenzamides.83... 

To be really satisfactory, a Friedel-Crafts alkylation requires one relatively stable secondary or tertiary carbocation to be formed from the alkyl halide by interaction with the Lewis acid, i.e. cases where there is not going to be any chance of rearrangement. Note also that we are unable to generate carboca-tions from an aryl halide - aryl cations (also vinyl cations, see Section 8.1.3) are unfavourable - so that we cannot nse the Friedel-Crafts reaction to join aromatic gronps. There is also one further difficulty, as we shall see below. This is the fact that introduction of an alkyl substitnent on to an aromatic ring activates the ring towards fnrther electrophilic substitution. The result is that the initial product from Friedel-Crafts alkylations is more reactive than the... 

Limitations of FC alkylation FC alkylations are hmited to alkyl halides. Aryl or vinyl halides do not react. FC alkylation does not occur on aromatic rings containing strong electron-withdrawing substituents, e.g. —NO, —CN, —CHO, —COR, —NH, —NHR or —NR group. Multiple substitutions often take place. Carhocation rearrangements may occur, which result in multiple products. 

In the same manner, a number of alkyl (43), vinyl (69, 203), aryl (204), and cyclopentadienyl (98, 100-102) complexes of gold(I) are cleaved by halogens to yield the corresponding gold(I) halides and the halo-substituted organic species. 

Vinyl Substitution with Alkyl, Aryl and Vinyl Halides 842... 

Normally, the most practical vinyl substitutions are achieved by use of the oxidative additions of organic bromides, iodides, diazonium salts or triflates to palladium(0)-phosphine complexes in situ. The organic halide, diazonium salt or triflate, an alkene, a base to neutralize the acid formed and a catalytic amount of a palladium(II) salt, usually in conjunction with a triarylphosphine, are the usual reactants at about 25-100 C. This method is useful for reactions of aryl, heterocyclic and vinyl derviatives. Acid chlorides also react, usually yielding decarbonylated products, although there are a few exceptions. Likewise, arylsulfonyl chlorides lose sulfur dioxide and form arylated alkenes. Aryl chlorides have been reacted successfully in a few instances but only with the most reactive alkenes and usually under more vigorous conditions. Benzyl iodide, bromide and chloride will benzylate alkenes but other alkyl halides generally do not alkylate alkenes by this procedure. 

Alkyl halides with (3-hydrogens generally undergo only elimination reactions under the conditions of the vinyl substitution (100 C in the presence of an amine or other base). Exceptions are known only in cases where intramolecular reactions are favorable. Even alkyl halides without (3-hydrogens appear not to participate in the intermolecular alkene substitution since no examples have been reported, with the exception of reactions with benzyl chloride and perfluoroalkyl iodides. 

Among the halides that react through this process are unactivated aromatic and heteroaromatic halides, vinyl halides, activated alkyl halides [nitroalkyl, nitroallyl, nitro-benzyl and other benzylic halides substituted with electron-withdrawing groups (EWG) as well as the heterocyclic analogues of these benzylic systems] and non-activated alkyl halides that have proved to be unreactive or poorly reactive towards polar mechanisms (bicycloalkyl, neopentyl and cycloalkyl halides and perfluoroalkyl iodides). 

The coupling takes place as if a carbanion (R ) were present and the carbanion attacked the alkyl halide to displace the halide ion. This is probably not the actual mechanism, however, because dialkylcuprates also couple with vinyl halides and aryl halides, which are incapable of undergoing SN2 substitutions. 

Metallated 1-ethoxy-1,3-dienes 697 and 712, obtained from the corresponding acetals by means of the LICKOR base, have been treated with alkyl halides, epoxides, carbonyl compounds, carbon dioxide and carboxylic esters affording ( )-l-substituted 1-ethoxy-1,3-dienes and, after hydrolysis, a,P-unsaturated carbonyl compounds1007-1010 (Scheme 186). Intermediates 697 and 712 have been transformed into the corresponding vinyl stan-nanes, which were submitted to Stille couplings with iodobenzene and benzoyl chloride823. 

Burdon et al. 31) have proposed that aryl and vinyl halides, but not alkyl halides, couple with copper compounds via a four-center transition state (XI). Nucleophilic substitution of vinylic bromides by organo-... 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

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