Reactions with 1,2-, 1,3-, and 1,4-Dienes

Reaction of conjugated dienes with aryl and alkenyl halides can be explained by the following mechanism. Insertion of a conjugated 1,3-diene into an aryl or alkenylpalladium bond gives the 7r-allylpalladium complex 330 as an intermediate, which reacts further in two ways. As expected, nucleophiles such as carbon nucleophiles, amines, and alcohols attack the 7r-allylpalladium intermediate to form the 1,4-addition product 331 and 1,2-addition product 332. In the absence of the nucleophiles, y5-H elimination occurs to afford the substituted 1,3-diene 333. In some cases, the substituted 1,3-diene 333 reacts again with aryl halide to form the it -allylpalladium 334. Subsequent elimination affords the 1,4-diarylated 1,3-diene 335. 

As early examples, Heck prepared the arylated conjugated dienes 333 and the 1,4-diarylated dienes 335. Also reaction of 2-phenylvinyl bromide with hex-atriene afforded l,10-diphenyl-l,3,5,7,9-decapentaene (336), although yield was low [136], 

Dieck reported preparation of the tetrahydrocarbazole 337 by heteroannulation of o-iodoaniline with 1,3-cyclohexadiene [137], As a recent example, heteroannulation of the o-iodoaniline derivative 338 with the conjugate dienyl sulfone 339 afforded the vinylogous 2-sulfonylindoline 340, which was converted to the indole derivative 341 by oxidative dehydrogenation [138]. Pd-catalyzed annulation of 1,3-dienes by o-iodoacetoxycoumain 342 offers a synthetic method for dihydro-furocoumarins. The dihydrofurocoumarin 343 was obtained by the reaction of 342 with 1-phenylbutadiene in 80% yield. After optimization, the uses of Pd(OAc)2, 

Ag2C03 in a mixture of dioxane and water provided good results [139]. Carboaimulation of diethyl o-iodophenylmalonate (344) with isoprene afforded 345 by 1,2-addition [140]. 

Unconjugated 1,4-cyclohexadiene (350) undergoes heteroannulation. Reaction of 350 with 349 is explained by carbopalladation to give 351. Dehydropalladation 

IJ Reactions nitlr 1,2-, 1.3-. ami 1.4-dienes. The reaction of conjugated dienes with aryl and alkenyl halides can be explained by the following mechanism. Insertion of a conjugated 1.3-diene into an aryl or alkenylpalladium bond gives the T-allvlpalladium complex 243 as an intermediate, which reacts further 

In the reaction of aryl and alkenyl halides with 1,3-pentadiene (248), amine and alcohol capture the 7r-allylpalladium intermediate to form 249. In the reactions of o-iodoaniline (250) and o-iodobenzyl alcohol (253) with 1,3-dienes, the amine and benzyl alcohol capture the Tr-allylpalladium intermediates 251 and 254 to give 252 and 255[173-175]. The reaction of o-iodoaniline (250) with 1,4-pen tadiene (256) affords the cyclized product 260 via arylpalladiuni formation, addition to the diene 256 to form 257. palladium migration (elimination of Pd—H and readdition to give 258) to form the Tr-allylpalladium 259, and intramolecular displacement of Tr-allylpalladium with the amine to form 260[176], o-Iodophenol reacts similarly. 

The TT-allylpalladiLim complexes formed as intermediates in the reaction of 1,3-dienes are trapped by soft carbon nucleophiles such as malonate, cyanoacctate, and malononitrile[ 177-179). The reaction of (o-iodophenyl-methyl) malonate (261) with 1,4-cyclohexadiene is terminated by the capture of malonate via Pd migration to form 262. The intramolecular reaction of 263 generates Tr-allylpalladium, which is trapped by malononitrile to give 264. o-[odophenylmalonate (265) adds to 1,4-cyciohexadiene to form a Tr-allylpalladium intermediate via elimination of H—Pd—X and its readdition, which is trapped intramolecularly with malonate to form 266)176]. 

When allene derivatives are treated with aryl halides in the presence of Pd(0), the aryl group is introduced to the central carbon by insertion of one of the allenic bonds to form the 7r-allylpalladium intermediate 271, which is attacked further by amine to give the allylic amine 272. A good ligand for the reaction is dppe[182]. Intramolecular reaction of the 7-aminoallene 273 affords the pyrrolidine derivative 274[183]. 

The reaction of the o-iodophenol 275 with an alkylallene affords the bcnzo-furan derivative 276[184], Similarly, the reactions of the 6-hydroxyallenes 277 and 279 with iodobenzene afford the tetrahydrofurans 278 and 280. Under a CO atmosphere, CO insertion takes place before the insertion of the allenyl bond, and a benzoyl group, rather than a phenyl group, attacks the allene carbon to give 280. Reaction of iodobenzene with 4,5-hexadienoic acid (281) affords the furanone derivative 282[185]. 

---

Given the tremendous variety of naturally occurring heterocyclic compounds, the development of elegant and efficient routes to the appropriately substituted ring systems is a formidable task. o-Amino- and o-hydroxy-substituted iodoarenes such as 121 can undergo a vast array of reactions with 1,2-. 1,3- and 1,4-dienes and ethenylcyclopropanes... 

Of the major methods for living radical polymerization, NMP appears the most successful for polymerization of the diene monomers. There are a number of reports on the use of NMP of diene monomers (B, I) with TEMPO,188,1103 861 4, cw and other nitroxides.127 High reaction temperatures (120-135 °C) were employed in all cases. The ratio of 1,2- 1,4-cis 1,4-trans structures obtained is similar to that observed in conventional radical polymerization (Section 4.3.2). 

We are being somewhat disingenuous here. If performed and interpreted correctly and with the appropriate ancillary phase-change enthalpy information, the enthalpy of formation of an arbitrary species by ion-molecule reaction chemistry and by combustion calorimetry must be the same. That the ionization potential of quinuclidine is higher than l,4-diazabicyclo[2.2.2]octane simply says that there is a stabilizing effect in the radical cation of the latter not found in the former. This information does not say that there is a stabilizing effect in the neutral molecular form of the latter not found in the former. After all, we trust the reader is not bothered by the fact that the ionization potential order of the cyclohexenes increases in the order 1,3-diene < 1,4-diene < 1-ene < 1,3,5-triene (benzene). 

Photo-[4+2] reactions of the dienone steroid 105 illustrates interesting regio-, stereo-, and site selectivities (Sch. 24) [75-78]. Reaction with 1-acetoxy-1,3-diene 106 gives trans adduct 107 in good yield, epimeric at the acetate. The trans cycloaddition was attributed to a triplet pathway rather than a twisted enone intermediate [75]. Reaction with 2,3-dimethyl-1,3-butadiene 108 leads to four [4+2] adducts, with reaction at both alkenes groups of the dienone. Note that the products of reaction at the y,5-alkene are both cis. 

However, reaction of acyclic dienamines with hydrazoic acid gives a mixture of products derived by 1,2-, 1,4- and 3,4 + 1,2-addition of HN3 to the diene system. In this case C-protonation is followed immediately by addition of the strongly nucleophilic azide anion, so that equilibrium of the C-protonated enamines cannot occur3c. Treatment of the morpholine dienamine of isophorone with trichloroacetic acid in boiling benzene resulted in decarboxylation and the 1,4-addition of a proton and the trichloromethyl anion. Basic hydrolysis of the adduct gave dienoic acid 54 (Scheme 4). 

Sulfonyl imides (78) are, like sulfenes, prepared by dehydrohalogenation of the corresponding sulfonyl chlorides (79) (usually called sulfamoyl chlorides). Like sulfenes, they take part in [2 + 2] and [4 + 2] cycloaddition reactions with electron-rich alkenes or with 1,3-dienes, yielding 1,2-thia-zetidine 1,1-dioxides (80)104 or dihydro-1,2-thiazines (81),105 respectively. 

The second example is an intermolecular crystal-state reaction. Cross-conjugated 1,5-disubstituted 1,4-dien-3-ones in solution undergo both cis-trans photoisomerization and photodimerization, yielding complex mixtures of products, including die all-trans-substituted cyclobutane 2 in the case of 1,5-diphenyl-1,4-pentadien-3-one. In contrast, dienones such as 3a in whose crystals adjacent molecules lie parallel and strongly overlapped react in the solid to give 3b as the sole photoproduct. This isomerically pure tricyclic diketone results, formally, from an eight-center dimerization. It is not formed in the reaction in solution, and could be prepared by other methods only with considerable difficulty (4). 

By far most of the reports on addition reactions of hetero-nucleophiles to activated dienes deal with sulfur-nucleophiles17,48,80,120-137, in particular in the synthesis of 7/3-sulfur-substituted steroids which, like their carbon-substituted counterparts (Section n.A), are of interest because of their ability to inhibit the biosynthesis of estrogens80,129-137. Early investigations17,120-122 concentrated on simple acyclic Michael acceptors like methyl sorbate and 2,4-pentadienenitrile. Bravo and coworkers120 observed the formation of a 3 1 mixture of the 1,6- and 1,4-adduct in the reaction of methyl sorbate with methanethiol in basic medium (equation 39). In contrast to this, 2,4-pentadienenitrile adds various thiols regioselectively at C-5, i.e. in a 1,6-fashion (equation 40)17,121,122, and the same is true for reactions of this substrate with hydrogen sulfide (equation 41), sodium bisulfite and ethyl thioglycolate17. 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

Reaction of polyfluorinated dienes with TFE resembles the reaction of polyfluoropropynes with fluoroethylenes. Polyfluorinated dienes react with TFE at ambient temperature in the presence of SbF5 catalyst [159].F-Heptadiene-2,4 (65) was obtained in 77% yield in reaction of F-pentadiene-1,3 and TFE along with small amounts of F-nonadiene-3,5. F-Hexadiene-2,4 reacts with TFE at 50 °C to give a mixture of isomeric octadienes 66 a, b ... 

---