Alkenyl halides nucleophilic reactions

Other reactions of synthetic utility can be observed when suitable nucleophiles are added to the reaction system. Typical examples of these nucleophiles are azide, cyanate, thiocyanate, and cyanide anions and thioanisole. Reactions using these nucleophiles provide a reaction path to functionalized vinyl derivatives. The transformations are successfully achieved by using triaryl-substituted alkenyl halides. The reactions with such nucleophiles provide an efficient path to heterocyclic compounds, among others. Some examples, such as the pyrroHnes, isoxazoHnes, isoquinolones, and thio derivatives, are prepared by this method and are shown in Equation 11.11. 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

Several types of Pd-catalyzed or -promoted reactions of conjugated dienes via TT-allylpalladium complexes are known. The Pd(II)-promoted oxidative difunctionalization reactions of conjugated dienes with various nucleophiles is treated in Chapter 3, Section 4, and Pd(0)-catalyzed addition reactions of conjugated dienes to aryl and alkenyl halides in this chapter. Section 1.1.1. Other Pd(0)-catalyzed reactions of conjugated dienes are treated in this section. 

The general mechanism of coupling reactions of aryl-alkenyl halides with organometallic reagents and nucleophiles is shown in Fig. 9.4. It contains (a) oxidative addition of aryl-alkenyl halides to zero-valent transition metal catalysts such as Pd(0), (b) transmetallation of organometallic reagents to transition metal complexes, and (c) reductive elimination of coupled product with the regeneration of the zero-valent transition metal catalyst. 

Cross-coupling of terminal acetylenes used as nucleophiles with aryl or alkenyl halides (referred to as the Sonogashira-Hagihara, or SH, reaction) is a versatile method of synthesis for acetylenic compounds, which are rapidly gaining importance as advanced new materials and building blocks for implementing unusual molecular architectures. 

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

Reactions of halides with 1,2-, 1,3- and 1,4-dienes generate 7i-allylpalladium intermediates, which react further with nucleophiles. The reaction of 1,3-dienes with aryl and alkenyl halides is explained by the following mechanism. The insertion of 1,3-diene to the aryl or alkenylpalladium bond generates 7r-allylpalladium complexes 54, which react further in several ways. As expected, nucleophiles such as carbon nucleophiles, amines, and alcohols attack the 7i-allylpalladium 54 to form the 1,4-... 

Aromatic carboxylic acids, a,/f-unsaturated carboxylic acids, their esters, amides, aldehydes and ketones, are prepared by the carbonylation of aryl halides and alkenyl halides. Pd, Rh, Fe, Ni and Co catalysts are used under different conditions. Among them, the Pd-catalysed carbonylations proceed conveniently under mild conditions in the presence of bases such as K2CO3 and Et3N. The extremely high toxicity of Ni(CO)4 almost prohibits the use of Ni catalysts in laboratories. The Pd-catalysed carbonylations are summarized in Scheme 3.9 [215], The reaction is explained by the oxidative addition of halides, and insertion of CO to form acylpalladium halides 440. Acids, esters, and amides are formed by the nucleophilic attack of water, alcohols and amines to 440. Transmetallation with hydrides and reductive elimination afford aldehydes 441. Ketones 442 are produced by transmetallation with alkylmetal reagents and reductive elimination. 

Problem 2.9. Alkenyl halides such as CH3CBr=CHCH3 do not undergo substitution upon treatment with a strongly basic nucleophile such as NI I2. What reaction occurs instead, and why does substitution not occur ... 

Other copper nucleophiles such as R CuLi and R2Cu(CN)Li2 also undergo substitution reactions with aryl and alkenyl halides. Retention of double-bond geometry about alkenyl halides is observed. The mechanisms of the reactions of these other Cu(I) nucleophiles are likely very similar to the one shown for the reaction of CuCN and ArBr. 

The reactions have a very wide scope. Acyl halides serve as substrates for Stille couplings in addition to the usual aryl and alkenyl halides however, most alkyl halides cannot be used as substrates. Like Pd-catalyzed carbonylations, reactions proceed most quickly when X = I and rather slowly when X = Cl. Again, triflates are also widely used, especially alkenyl triflates, which are easily prepared from the ketones. The nucleophile may be C(sp), C(sp ), or C(sp ), and nucleophiles other than C nucleophiles (e.g., Me3Sn—SnMes and R2N— Na) may also be used. 

A main reaction path of the 2,3-butadien-l-ols 379 with aryl and alkenyl halides in DMSO using DPPE is /1-H elimination, and /I,y-unsaturated aldehyde 380 or ketones are obtained [148], However, allenes bearing nucleophilic centers undergo heterocyclization under different conditions and numerous applications have been reported. 

The cw-heteroannulation of alkyne extended to alkenyl halides 83 containing a proximate nucleophilic center to yield the heterocycles 86 by the reactions via 84 and 85 similar to those summarized in Scheme 3.9 (Scheme 3.10). 

Pd-catalyzed nucleophilic displacement of carbon electrophiles with CN provides an efficient synthetic method of aryl or alkenyl cyanides from the corresponding aryl or alkenyl halides or triflates. Compared to the Rosenmund-von Braun reaction, the advantages of the present method are the necessarily mild reaction conditions, compatibility with a variety of functional groups, and simple work-up procedures. 

This type of reaction has been developed by employing aryl and alkenyl halides or triflates containing proximate nitrogen or oxygen nucleophiles and internal acetylenes. 

In 1985, Ahmar Cazes, and Gore disclosed the cocyclization reaction of nucleophile-containing allenes with aryl and 1-alkenyl halides to form five-membered and/or three-membered carbocycles. With unsubstituted vinyl bromide, only the vinyl cyclopropane derivative 109 was formed (Scheme 35). 

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