Aryl halides vinyl substitutions

A complementary approach for cross-couplings with allenes was applied by using metallated allene species instead of allenyl halides, which have already been discussed in Sect. 14.2.1. Since allenyllithium compounds are readily available by deprotonation of allenes with n-butyllithium, successful cross-coupling reactions between lithiated allenes such as 54 or 57 and aryl or vinylic halides allowed convenient routes to aryl- and vinyl-substituted allenes, e.g. 55, 58 and 60 (Scheme 14.15) [30],... 

Aryl- and vinyl-substituted acetylenes. Acetylene or monosubstituted acetylenes react with aryl or vinyl halides in the presence of this palladium(O) complex as catalyst and of base (CH30Na) in DMF at 40-80° to give aryl- or vinyl-acetylenes ... 

The conversion of acetylene or monosubstituted acetylenes into aryl- and vinyl-substituted acetylenes by reaction with aryl and vinyl halides,... 

Several of the new reactions of unsaturated boranes are notable. Vinylboranes can be induced by a Pd catalyst to couple with aryl halides, giving substituted styrenes in high yield,and with vinyl bromides to give E,E-dienes stereo-specifically. " Allylboranes (60) give eryt/iro-alcohols (61) in high stereoselectivity on reaction with RCHO, and S-alkynyl-9-BBN react with RN=C=0 to give (62). ... 

Unlike elimination and nucleophilic substitution reactions, fonnation of organo-lithium compounds does not require that the halogen be bonded to 5/) -hybiidized car bon. Compounds such as vinyl halides and aryl halides, in which the halogen is bonded to sp -hybiidized carbon, react in the sane way as alkyl halides, but at somewhat slower rates. 

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... 

The palladium-catalyzed annulation of alkynes by functionally-substituted aryl and vinylic halides or triflates provides a veiy convenient and efficient approach to a wide variety of heterocycles and carbocycles. This chemistry has lead to the discovery of a number of novel palladium-catalyzed processes in which the palladium migrates from one carbon to another within the molecule providing a unique way to form carbon-carbon bonds in remote locations within the same molecule. 

Ternary Pd-catalyzed coupling reactions of bicyclic olefins (most often norbor-nadiene is used) with aryl and vinyl halides and various nucleophiles have been investigated intensively over the past few years [44]. A new approach in this field is to combine Heck and Suzuki reactions using a mixture of phenyliodide, phenyl-boronic acid and the norbornadiene dicarboxylate. Optimizing the conditions led to 84% of the desired biphenylnorbornene dicarboxylate [45]. Substituted phenyl-iodides and phenylboronic acids can also be used, though the variation at the norbornadiene moiety is highly limited. 

Simple reaction occurs with aryl halides only when the ring is sufficiently substituted with electron-withdrawing functions to allow attack by the nucleophilic phosphorus.53-56 Generally, reaction with aryl halides requires the presence of a Lewis acid catalyst or some other means of reaction initiation. These reactions will be considered in detail in Chapter 6 of this work. Interestingly, while reactions involving vinylic halides seem to correlate with those of aromatic halides (see Chapter 6), acetylenic halides undergo facile reaction with these phosphorus reagents.57 58... 

Isomerization of 1,3-dienes (12, 36).3 The 1,5-hydrogen shift in isomerization of 1,3-dienes catalyzed by (naphthalene)Cr(CO)3 (1) can be used for synthesis of aryl-substituted exocyclic alkenes, which are not readily available by coupling of aryl halides with exocyclic vinyl halides. 

The reduction of aryl-substituted vinyl halides by electrochemically generated aromatic anion radicals has also been investigated in DMF (Gatti et al., 1987). Counter-diffusion behaviour at low driving forces (pp. 34, 35) does not appear as clearly as in the case of aryl halides (Fig. 11). However, analysis of the log k vs E° plot according to a quadratic activation-driving force relationship gave standard potential and intrinsic barrier values that... 

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. 

More recently, the a-trifluoromethyl substituted /i-ethoxyvinyl zinc reagent has been prepared in a similar way and coupled with aryl or vinyl halides in the presence of Pd(PPh3)4 [171] (Scheme 61). 

The report by Bunnett and coworkers107 of substitution of halide by MeCOCth" or PhS- ions in vinyl bromides or iodides appears to be the only synthetic application of the SrnI reaction at vinylic sites. The reactions, particularly with benzenethiolate ion, are slower than those of aryl halides and the yields are not as good. Tautomers or mixtures of products result in the reactions with MeCOCH2 (e.g. equation 32). 

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

Vinyl Substitutions with Carboxylic Acid Halides, Aryl Sulflnates and Arylsulfonyl Chlorides 856... 

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. 

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