Tetraene formation

Tetraene 4 (Scheme 1.3), when treated with 40 mol % of triflic acid in methylene chloride at -23 °C for 1 h, gives the adducts 5 and 6 in a 1 1 ratio as the main reaction products. The formation of these adducts has been justified [21] by a stepwise mechanism that requires an initial reversible protonation of 4 to produce the allyl cation 7, which then cyclizes to 8 and 9 in a non-reversible process. Deprotonation of 8 and 9 gives 5 and 6, respectively. 

The nature of the solvent is very important in these reactions and evidence was obtained for the formation of tetraenes, including isolation of a crystalline sample in one case. The reactions of... 

Finally, Parker and coworkers [101] were able to use this approach for the total synthesis of SNF4435C (6/1-190) (Scheme 6/1.51). The Pd-catalyzed reaction of 6/1-191 and 6/1-195 gave a 4 l-mixture of 6/1-190 and its endo-diastereomer 6/1-199 in 53% yield. In this transformation, the tetraene 6/1-196 can be assumed as intermediate, which theoretically could undergo an 8jt/6jt electrocyclization to give the endo-products via conformation 6/1-197 and the exo-products via conformation 6/1-198. However, only the two endo-products 6/1-190 and its diastereomer 6/1-199 are found, and not 6/1-200, which is consistent with the most likely nonenzymahc formation of 6/1-190 and its diastereomer in Nature from their co-metabolite spectabilin. 

One of the most recent developments in the field of Ni-catalyzed reactions of alkyl halides with organozinc derivatives is a study of Terao et al.411 They reported the use of three additives in the couplings 1,3-butadiene, N,N-bis(penta-2,4-dienyl)benzylamine 308a, and 2,2-bis(penta-2,4-dienyl)malonic acid dimethyl ester 308b. Addition of tetraene 308b to the reaction mixtures significantly increased the product yields (Scheme 157). The remarkable effect of these additives was explained by the formation of the bis-7r-allylic complex 309 as the key intermediate (Scheme 158). 

In contrast to 154 the isomeric bicyclo[4.4.1]undeca-3,5,8,10-tetraene-2,7-dione /bicyclic structure. Formation of the bis-Grignard reagent 163... 

The tetracyclic alcohol 179 is produced by the action of boron trifluoride etherate or tin(IV) chloride on the oxirane 178 (equation 85)95. A similar cyclization of the oxirane 180 yields DL-<5-amyrin (181) (equation 86)96. In the SnCLt-catalysed ring-closure of the tetraene 182 to the all-fraws-tetracycle 183 (equation 87) seven asymmetric centres are created, yet only two of sixty-four possible racemates are formed97. It has been proposed that multiple ring-closures of this kind form the basis of the biosynthesis of steroids and tetra-and pentacyclic triterpenoids, the Stork-Eschenmoser hypothesis 98,99. Such biomimetic polyene cyclizations, e.g. the formation of lanosterol from squalene (equation 88), have been reviewed69,70. 

C-C bond formation mediated by silane.6,6a 6f With respect to the development of intramolecular variants, these seminal studies lay fallow until 1990, at which point the palladium- and nickel-catalyzed reductive cyclization of tethered 1,3-dienes mediated by silane was disclosed. As demonstrated by the hydrosilylation-cyclization of 1,3,8,10-tetraene 21a, the /rarcr-divinylcyclopentanes 21b and 21c are produced in excellent yield, but with modest stereoselectivity.46 Bu3SnH was shown to participate in an analogous cyclization.46 Isotopic labeling and crossover experiments provide evidence against a mechanism involving initial diene hydrosilylation. Rather, the collective data corroborate a mechanism involving oxidative coupling of the diene followed by silane activation (Scheme 15). 

Kinetics and mechanisms of complex formation have been reviewed, with particular attention to the inherent Fe +aq + L vs. FeOH +aq + HL proton ambiguity. Table 11 contains a selection of rate constants and activation volumes for complex formation reactions from Fe " "aq and from FeOH +aq, illustrating the mechanistic difference between 4 for the former and 4 for the latter. Further kinetic details and discussion may be obtained from earlier publications and from those on reaction with azide, with cysteine, " with octane-and nonane-2,4-diones, with 2-acetylcyclopentanone, with fulvic acid, and with acethydroxamate and with desferrioxamine. For the last two systems the various component forward and reverse reactions were studied, with values given for k and K A/7 and A5, A/7° and A5 ° AF and AF°. Activation volumes are reported and consequences of the proton ambiguity discussed in relation to the reaction with azide. For the reactions of FeOH " aq with the salicylate and oxalate complexes d5-[Co(en)2(NH3)(sal)] ", [Co(tetraen)(sal)] " (tetraen = tetraethylenepentamine), and [Co(NH3)5(C204H)] both formation and dissociation are retarded in anionic micelles. 

Photolysis (245 nm) of tetrazolo[l,5-/ ]pyridazine 21 in an argon matrix at 16 K leads to nitrogen extmsion and ring opening to form (2Z)-4-diazobut-2-enenitrile 22. Further photolysis produces predominantly cycloprop-2-ene-1-carbonitrile 23 and small amounts of l,3,7-triazacyclohepta-l,2,4,6-tetraene 24. No formation of triplet pyrid-azine-3-nitrene 25 is observed (Scheme 5) <2003PCP1051>. 

The use of ring-closing metathesis for the preparation of unsaturated heterocyles is now established as a routine method for single cyclisation steps, and the method has been extended to the preparation of bicyclic systems in a single step One example is the cyclisation of the tetraene 43 leading to formation of tetrahydrooxepine 44 in 59% yield <99JOC3354>. The method is equally applicable to the formation of five- and six-membered systems. 

The thermal isomerization of cyclooct tetraene epoxide hoe been studied at 260° by Btichi and Burgess,2012 who observed the formation uf threo ieomerio aldehydoa (Eq. 460a), one of which may be the elusive compound norcaradieno carboxaldehyde. 

The reader will recall equations 9 and 10 are generally ca 5 and 42 kJ moT1 endothermic. However, we generally lack enthalpies of formation for the compounds with the same affixed X as the above with which to compare reactions 9,10 and 16. Possibly, though very unlikely, the reaction of two conjugated dienes to form a linearly conjugated tetraene will show considerable additional stabilization. We note one comparison of related 4 and 3 chromophore species. Consider the de-acetylenation reaction... 

The catalytic desymmetrization shown in Scheme 5 involves a meso-tetraene substrate optically pure unsaturated siloxane 23 is obtained in >99% ee and 76% yield [16]. The unreacted siloxy ether moiety is removed to afford optically pure 24. Mo-alkylidenes derived from both enantiotopic terminal alkenes in 22 are likely involved. Since the initial metal-alkylidene generation is rapidly reversible, the major product arises from the rapid RCM of the matched segment of the tetraene. If any of the mismatched RCM takes place, a subsequent and more facile matched RCM leads to the formation of meso-bicycle. Such a byproduct is absent from the unpurified mixture containing 23, indicating the exceptionally high degree of stereodifferentiation induced by the chiral Mo com-... 

Gorman and Gassman905 have shown that undecatetraenes undergo cyclization (intramolecular Diels-Alder reaction) in the presence of triflic acid to provide bicyclo[4.3.0]nonyl [Eq. (5.332)], bicyclo[4.4.0]decyl, and bicyclo[5.4.0]undecyl [Eq. (5.333)] ring systems, depending on the methyl-substitution pattern. On the basis of a comparative study with varied tetraenes, they concluded that product formation, at least in some cases, could be best interpreted by a stepwise... 

Cyclization of the tetraene 236 with trifluoroacetic acid in dichlorometh-ane at temperatures of -50° to -25° gave yields of 237 up to 81% when Ar=c,-naphthyl (91). The stereospecific formation of the cis-fused A/B ring junction is a direct consequence of stereoelectronic control. Indeed, in the formation of the cis junction, the newly formed bond (238 - 239) is pseudo-axial and is therefore maintained parallel to the v-orbital of the cyclo-hexenyl double-bond. Such orbital overlap is impossible in forming an A/B... 

The oxidation of 5.20 (by air, nitric acid, iron(m) etc.) results in electron loss from the nitrogen-centred radical and the formation of an iron(n) nitrenium species 5.21 (Fig. 5-36), which then undergoes deprotonation to yield an iron(n) complex of a tetraene 5.22 (Fig. 5-37). 

One of the secondary reactions that ortho adducts from alkenes and benzene or benzene derivatives may undergo is formation of a tetraene, by complete ring opening. The process was first described by Atkinson et al. [73] in their report on the ortho photocycloaddition of benzonitrile to 2-methylbut-2-ene (Scheme 49). They did not detect the tetraenes among the irradiation products, but found it when they pyrolyzed or photolyzed the ortho adduct. Pyrolysis at 128°C gave 53% alkene, 6% benzonitrile, and 41% tetraene photolysis caused almost complete reconversion (90%) to arene and alkene, whereas formation of tetraene occurred to the extent of 8-10%. Most likely a mixture of cis and trans isomers of 2-methyl-... 

In the formation of tetraenes from bicyclo[4.2.0]octa-2,4-dienes, two bonds are broken. This may occur in one concerted reaction which can be regarded as a retro [2 + 2] cycloaddition. It is also possible that the central bond, being part of a cyclohexadiene system, is the first one to break in a thermal, concerted disrota-tory process that leads to a 1,3,5-cyclooctatriene derivative. Ring opening of the cyclooctatriene then might take place photochemically, again disrotatory, to produce a tetraene. This two-step sequence was first observed by Mirbach et al. [114] in their study of the photocycloaddition of the two parent molecules benzene and ethene. The same explanation for the formation of a tetraene was given by Nuss et al. [160] in their report on the intramolecular ortho photocycloaddition of ( )-6-(2-methoxyphenyl)-5,5-dimethyl-2-hexenenitrile (see Scheme 40). 

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