Dienes from vinyl halides

Palladium acetate triarylphosphine complexes catalyze the addition of vinylic groups from vinylic halides to olefinic compounds in the presence of amines. Conjugated dienes are major products from 0,/3-unsaturated acids, esters, or nitriles while unactivated olefinic compounds react best in the presence of secondary amines where allylic amines are major products. The reactions are usually regio- and stereospecific. The synthetic utility of the reaction is illustrated with a wide variety of examples. 

The mechanism and stereochemsitry of dehydrohalogenations from vinyl halides have been extensively reviewed - It should however be pointed out that the effects of particular bases and solvents and of temperature cannot always be predicted with confidence as to rate of reaction and product distribution (acetylene, allene, diene). Therefore a variety of combinations of base, solvent and reaction conditions should be tried in order to obtain satisfactory results. 

Synthesis of dienes [1, 169, before references], Tetrahydrofurane solutions of vinylmagnesium halides are readily accessible from vinyl halides by the method of Normant.19 Kauffmann and Sahm20 found that when a THF solution of the vinyl-magnesium compound (1) is treated at —60° to —40° under nitrogen with a suspension of cuprous chloride an intensely green or red solution is obtained which presumably contains a vinylcopper compound. When the mixture is warmed to... 

Dieck, H.A. and Heck, R.R (1975) A palladium-catalyzed conjugated diene synthesis from vinylic halides and olefinic compounds J. Org. Chem., 40, 1083-90. 

Among special chemical methods that facilitate the Diels-Alder reaction can be included the temporary metal connection strategy [101] that is illustrated in Table 4.27. Si, Mg and A1 are used as temporary connectors of diene and dienophile moieties. The cycloaddition occurs easily due to its intramolecular nature and because the dienophilic component of reagent is now formally a vinyl carbon ion (i.e. a vinyl carbanion in 154 with M = AlEt ). Thus the metal-tethered 154, prepared from lithium alkoxide of 153 with the suitable metal vinyl halide, gives, by heating, the cycloadducts 156 and 157, through the... 

The consecutive reaction of vinyl halides and alkenes with activated methylene systems [42] in the presence of a palladium catalyst and phase-transfer catalyst results from the addition of the methylene carbanion with the initially formed Heck product (Scheme 6.31) an intramolecular version of the reaction leads to the formation of bicycloalk-l-enes (Scheme 6.31) [42], The analogous combined coupling reaction of iodoarenes and activated methylene compounds with non-conjugated dienes under similar conditions forms the monoalkene (Scheme 6.31) [43]. 

If in the reactions of vinyl halides with alkenes a sterically unhindered secondary amine is used as base, different products are obtained (equation 192).6SO Incorporation of the amine occurs to give unsaturated tertiary amine as the major product. The conjugated dienes which would be expected from reaction (191) are present as minor products. 

The choice as to which fragment of the molecule to be synthesized should be the vinylic halide and which should be the olefin will depend on several factors. In the cases where elimination to form conjugated dienes is the favored reaction, either possible combination of vinylic halide and olefin may produce the same diene however, different intermediates are involved and in some instances different products may be formed. The situation is more complex when allylic amines are produced since these products always will be different from the two different combinations of reactants. For example, Z-... 

Additions to functionalized three-carbon olefins have been studied extensively. We have used methyl acrylate as a standard olefin since it always reacts only at the terminal carbon and the a,/3-double bond in the product is always trans. The stereospecificity of its reactions with vinylic halides varies with structure. The simple 1-halo-l-alkenes with methyl acrylate under normal conditions give mixtures of E,Z- and E,E-dienoates. The reaction is more selective with the bromides than with the iodides and the stereoselectivity increases with increasing triphenylphosphine concentration. This occurs because the excess phosphine displaces the hydridopalladium halide group from the diene 7r-complex before readdition to form the ir-allylic species occurs (see Equation 6). The disubstituted vinylic bromides react stereospecifically with methyl acrylate (4). 

The Suzuki reaction was a key step in the synthesis of bombykol, the sex pheromone of the female silkworm moth, and humulene, a lipid isolated from hops, as shown in Figure 26.1. The synthesis of humulene illustrates that an intramolecular Suzuki reaction can form a ring. Sample Problem 26.2 shows how a conjugated diene can be prepared from an alkyne and vinyl halide using a Suzuki reaction. 

Vinyl halides represent yet another important class of intermediates in the conversion of ketones to alkenes. The most widely applied conditions for the conversion of ketones into vinyl halides are those developed by Barton et a/. ° for the conversion of 3p-acetoxyandrost-5-ene-17-one into 3P-hydroxyandrosta-5,16-diene (Scheme 44). These conditions of vinyl halide formation and subsequent reduction have been useful in a number of steroid systems for the introduction of a A -carbon-carbon double bond and have been shown to be compatible with such functional groups as alcohols, isolated double bonds and acetals. The scope of vinyl iodide formation from hydrazones has been studied by Pross and Stemhell, and recently the original reaction conditions were improved by using sterically hindered guanidine bases rather than triethylamine. Haloalkenes have also been prepared from the corresponding ketones by treatment with iodoform and chromium chloride or with phosphorous penta-halides. ... 

Whether the reaction is inter- or intramolecular, the Heck reaction generates vinyl(hetero)arenes or dienes from an alkene and a (hetero)aryl or alkenyl halide [130]. This reaction has great versatility and is applicable to a wide range of aryl and alkene species. Mechanistically, the Heck reaction varies from that depicted in Fig. 4.3. While the oxidative addition of the halogen species occurs, the transmetalation step is replaced by the coordination of the alkene. This is followed by a migratory insertion which essentially substitutes for the cross-coupling step. The product is released not by a reductive elimination, but by a 3-hydride elimination sequence (Fig. 4.5). 

Heck reactions involving nonaromatic components are particularly versatile synthetic processes. For example, 1,2,4-trienes and l,2-dien-4-ynes are readily prepared from propargyl carbonates." Intramolecular Heck cyclization followed by Diels-Alder or nucleophilic attackleads to bicyclic products. Substituted pyrrolidines and piperidines are formed by coupling of alkenyl sulfonamides with vinylic halides. ... 

Conjugated dienes undergo hydroperfluoroalkylation with perfluoroalkyl iodides and zinc in the presence of titanium catalysts 02 Yields are moderate to good (52-74%) but stereoselectivity is low. From allylic halides functionalized on the a-vinylic position (TMS, carboxylate, phosphonate), additions to terminal alkynes provide functional dienes, used in further synthetic reactions leading to lactones and carboxylic or phosphonic esters.228... 

Even simple alkenes, such as 1-hexene 9.270, can yield ir-allyl complexes on reaction with vinyl halides under Heck conditions (Scheme 9.75). This is only apparent when a nucleophile is present, such as a secondary amine or a malonate anion. The ir-allyl complex 9.279 is generated by isomerization of the corresponding T -complex 9.278 that is itself generated by a -hydride elimination-reinsertion sequence from the initial insertion product 9.275. Nucleophilic attack on the Tr-allyl complex gives the three component coupling product 9.273, while the Heck product, diene 9.272, can arise from dissociation from t -complex 9.276 or p-hydride elimination from the -intermediate 9.278. Again, the reaction is particularly effective in an intramolecular sense. °°... 

Scheme 14.4. Vinyl halides react with alkyllithium to afford vinyllithium, and then a reaction with MnCl2 affords the manganeselithium compound. RI produced from the formation reaction of vinyllithium reacts with the manganeselithium compounds to afford the alkylmanganese compounds. The alkyl group of the alkyl-manganese compounds is easily eliminated. Then the coupling reaction of one vinyl group eliminated produces mole of diene [83].

Bombykol is a sex pheromone secreted by the female silkworm moth Bombyx mori to attract mates. Bombykol s structure was elucidated in 1959 using 6.4 mg of material obtained from 500,000 silkworm moths. One step in an efficient synthesis of bombykol is the Suzuki reaction, a stereospecific carbon-carbon bond-forming reaction between a vinylborane and a vinyl halide to form a conjugated diene. In Chapter 26, we learn how to prepare a variety of substrates using novel carbon-carbon bond-forming reactions. 

---