Dienes, from allylic halides

Radical reactions are used industrially in many C-C bond-forming reactions, particularly the polymerisation of olefins. Such methods are beyond the scope of this book. Some simpler molecules are made by radical dimerisation. Diene (21), used in the manufacture of pyrethroid insecticides, is a dimer of the stable allylic radical (22) and is made industrially at ICI from allylic halide (23). 

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... 

Conjugated dienes can be prepared from allylic halides via an elimination process. 

A similar transformation results when trimethylsilyloxy-substituted allylic halides react with silver perchlorate in nitromethane. The resulting allylic cation gives cycloaddition reactions with dienes such as cyclopentadiene. The isolated products result from desilyla-tion of the initial adducts ... 

Whereas simple olefins are not usually made by elimination from halides, conjugated systems are frequently obtained in this way. The cases of a- and j5-halo ketones and their vinylogues have already been covered. Allylic halides may also be eliminated to form dienes, for example, the 2,4-diene (109)... 

Conjugated dienes can be prepared by some of the methods previously discussed for preparing alkenes (Sections 11.7-11.10). The base-induced elimination of HX from an allylic halide is one such reaction. 

Monodehydrohalogenation of allylic halides is another classical method for diene synthesis24. This method is complementary to double dehydrohalogenation as both the 1,2-dihalides and allylic halides are readily accessed from alkenes. The commonly employed protocol for diene synthesis, particularly for cyclic 1,3-dienes, is through the allylic monobromination of the alkene with A-bromosuccinimide or related reagents followed by dehydrobromination with hindered bases such as DBN or DBU (equation l)25. 

The first reported radical reaction promoted by tellurium reagent was probably the conversion of allylic halides into the coupled 1,5-dienes by treatment with telluride anions. The reaction, which gives the best results when employing the reagent prepared in situ from elemental tellurium and lithium triethylborohydride, proceeds through the intermediacy of the thermally unstable bis-allylic telluride followed by extrusion of tellurium and coupling of the formed allylic radicals. 

In another method for the coupling of two different allylic groups,1346 a carbanion derived from a p.-y-unsaturated thioether couples with an allylic halide.1347 The product contains an SPh group that must be removed (with Li in ethylamine) to give the 1,5-diene, but this... 

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. 

Abstraction of chloride from a vinylpalladium complex by silver acetate has been reported,45 as well as halide abstraction by silver triflate from arylpalladium halides.46 More interestingly in the context of creating C-C bonds, silver perchlorate was able to promote the reaction of (r -aryl)palladium bromide with dienes. Silver-promoted bromide abstraction led to the formation of (r 1-r 2-enyl)palladium complexes, which evolved further through the regioselective formation of a C-C bond between the aryl group and the former diene. Reactions with nonconjugated dienes suggested that the reaction proceeds via carbometallation of the less crowded double bond. Isomerization and (3 elimination led to a (ri3-allyl)palladium complex (Scheme 10.26).47... 

This volume also gives a description of the evolution in Nd-catalyzed polymerization of dienes from the early works to the current state of the art. The authors highlight the tremendous variety of investigated catalyst systems and both articles order the catalyst systems according to the type of anions carboxylates, alcoholates, halides, hydrides, phosphates, phosphonates, allyls, tetraalkylaluminates, cyclopentadienyl complexes, amides, acetylacetonates,... 

The complex formed on addition of cuprous iodide to a solution of a lithium dialkylamide in ether or tetrahydrofuran is effective in the reductive coupling of allylic halides to give 1,5-dienes with preservation of stereochemistry. This method has been used5 for the stereospecific synthesis of all-trans-squalene and (E,Z,Z,E) squalene from (E,E)- and (Z,JE)-farnesyl bromides, respectively. In an attempted synthesis of (3S)-squalene-2,3-epoxide, 4-[(4R)-2,2,5,5-tetramethyl-l,3-dioxolan-4-yl]butan-2-one (1) and the phosphonium iodide (2) were prepared.6 Unfortu-... 

Reductive coupling of allylic halides. This cobalt complex (1 equiv.) effects reductive coupling of allylic halides to form 1,5-dienes with preservation of the geometry of the double bonds/ The major product from coupling of terpenoid allylic halides is that formed by head-to-head coupling. The triphenylphosphine liberated during the reaction is removed as methyltriphenylphosphonium iodide, obtained by reaction with methyl... 

Substitution reactions of allylic halides show diverse character according to the reagent and the position of the allylic system. In buffered aqueous solutions the 3 a- and 3 3-chloro-A -compounds 7) and (8), and also the 4/5-chloro-AS-(10) and 6ji -chloro-A4 compounds (ii) clearly react through common allylic cations (9 and 12, respectively). The product patterns are what one would expect from nucleophilic attack upon these cations by water, accompanied in the case of the C<3) C(4)-C(5) cation (9) by proton abstraction to give a diene. This cation exhibits no preference for either 3 a- or 3jS-attack of the nucleophile but the C(4>-C(5) C(6) cation 12) is attacked... 

Selective reduction of allyl sulfides implies that no scrambling of the carbon-carbon double bond occurs during the process. Effectively this has proved to be the case especially when lithium in ethylamine is used, and the method has allowed the regio- and stereo-selective synthesis of a large variety of 1,5-dienes including squalene (Scheme 25, entry a), mukapolide (Scheme 25, entry b), dendrolasin (Scheme 25, entry c), the basic nucleus of crassin acetate (Scheme 25, entry d) from 7,7-dialkylallyl sulfides and allyl halides, and also of 1,5-enynes " from propargyl sulfides and allyl halides (Scheme 34, entry b). 

For the more reactive allylic halides 4 a and 4 b the salt of diethyl hydrazinodicarboxylate was used as the nucleophile in preference to hydrazine.Deazetization of the resultant 4,5-dihydro-37/-pyrazoles 5 gave a mixture of alkylidenecyclopropanes 6 and 7. It should be noted that attempts to make 4-isopropylidene-4,5-dihydro-37/-pyrazole (5 b) by the more obvious route (by the reaction of diazomethane with 3-methylbuta-l,2-diene) failed. This route has been modified for the synthesis of various deuterated derivatives of 5 and used to make optically active (3/ ,57 )-3,5-dimethyl-4-methylene-4,5-dihydro-3/f-pyrazole, but all of the cyclopropanes produced from thermolysis of this compound were racemic. A similar route has also been used in the synthesis of 7,7-dimethyl-6b,7a-dihydro-7//-cycIopropa[fl]acenaph-thylene. ... 

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