1,2,7-Trienes cyclization

Figure 10.27 summarizes the energy relationships for the four-, six-, and eight-electron systems relative to the polyenes. We see that for cyclobutene-1,3-butadiene, ring opening is favored and the is 32 kcal/mol. The is similar for the 1,3,5-triene cyclization (30 kcal/mol), but ring closure is favored. The E drops to 17.0 kcal/mol for the Z,Z-l,3,5,7-octatriene to 1,3,5-cyclooctatriene cyclization, whereas the E for the reverse reaction is 28.2 kcal/mol. 

In Shea s approach to the polyhalogenated cyclohexane 87, derived from a red marine alga, Plocamium sp., a Type II IMDA reaction utilizing a disposable (allyl)silyl tether was used as a key step [29nj. The triene cyclization precursor 88 was readily prepared and underwent Diels-Alder reaction in 74% yield with the expected, complete regiocon-trol affording exclusively bicycle 89. The rigid, bicyclic framework of the cycloadduct... 

In addition to these monosubstituted examples, an excellent comparison of dienophiles bearing more than one electron-withdrawing group has appeared (4). Still, this area is not yet entirely understood (8). It should be pointed out that some trienes cyclize so rapidly ([5]-in this case, probably under acid catalysis) that kinetic studies would be difficult. 

Liotta, D. and Ott, W. (1987) Triene cyclizations. The total synthesis of pallescensin A. Synth. Commun., 17,1655-1665. 

The achiral triene chain of (a//-rrans-)-3-demethyl-famesic ester as well as its (6-cis-)-isoiner cyclize in the presence of acids to give the decalol derivative with four chirai centres whose relative configuration is well defined (P.A. Stadler, 1957 A. Escherunoser, 1959 W.S. Johnson, 1968, 1976). A monocyclic diene is formed as an intermediate (G. Stork, 1955). With more complicated 1,5-polyenes, such as squalene, oily mixtures of various cycliz-ation products are obtained. The 18,19-glycol of squalene 2,3-oxide, however, cyclized in modest yield with picric acid catalysis to give a complex tetracyclic natural product with nine chiral centres. Picric acid acts as a protic acid of medium strength whose conjugated base is non-nucleophilic. Such acids activate oxygen functions selectively (K.B. Sharpless, 1970). 

The cyclization of the enediynes 110 in AcOH gives the cyclohexadiene derivative 114. The reaction starts by the insertion of the triple bond into Pd—H to give 111, followed by tandem insertion of the triple bond and two double bonds to yield the triene system 113, which is cyclized to give the cyclohexadiene system 114. Another possibility is the direct formation of 114 from 112 by endo-rype. insertion of an exo-methylene double bond[53]. The appropriately structured triyne 115 undergoes Pd-catalyzed cyclization to form an aromatic ring 116 in boiling MeCN, by repeating the intramolecular insertion three times. In this cyclization too, addition of AcOH (5 mol%) is essential to start the reaction[54]. 

Electrocyclic reactions of 1,3,5-trienes lead to 1,3-cyclohexadienes. These ring closures also exhibit a high degree of stereospecificity. The ring closure is normally the favored reaction in this case, because the cyclic compound, which has six a bonds and two IT bonds, is thermodynamically more stable than the triene, which has five a and three ir bonds. The stereospecificity is illustrated with octatrienes 3 and 4. ,Z, -2,4,6-Octatriene (3) cyclizes only to cw-5,6-dimethyl-l,3-cyclohexadiene, whereas the , Z,Z-2,4,6-octa-triene (4) leads exclusively to the trans cyclohexadiene isomer. A point of particular importance regarding the stereochemistry of this reaction is that the groups at the termini of the triene system rotate in the opposite sense during the cyclization process. This mode... 

Aqueous hydrofluoric acid dissolved in acetonitrile is a good catalyst for intramolecular Diels-Alder reactions [9] This reagent promotes highly stereoselective cyclizations of different triene esters (equation 8) The use of other acids, such as hydrochloric, acetic, and trifluoroacetic acid, results in complete polymerization of the starting trienes [9] (equation 8)... 

In the initial step, neocarzinostatine 8 (simplified structure) is converted to the cyclization precursor 9, which contains a cumulated triene unit. The reaction... 

Figure 30.7 Photochemical cyclizations of conjugated dienes and trienes. The two processes occur with different stereochemistry because of their different orbital symmetries.

Our strategy is based on the premise that the 31-membered ring and the conjugated triene array of the natural product could be fashioned simultaneously by a tandem inter-/intramolecular Stille coupling. Moreover, the mild conditions under which Stille couplings can be performed fueled hopes that the crucial stitching cycliza-tion could be conducted on a fully deprotected seco bis(vinyl iodide) (see 145, Schemes 40 and 54) the stitching cyclization would thus be the final operation in the synthesis. 

Recently reported289 is an analogous reaction involving the acid-catalyzed cyclization of (lZ,3 ,5Z)-l,6-diphenylhexa-l,3.5-triene-l,6-diamine (14) in refluxing toluene to 2,7-diphenyl-3//-azepine (15). The l,6-bis(4-tolyl) and 1,6-dibenzyl derivatives behave similarly, but give substantially lower yields (14-18%). 

Closely related to the polyepoxide cascade procedure for the synthesis of polycyclic systems is Corey s biomimetic-type, nonenzymatic, oxirane-initiated (Lewis acid-promoted) cation-olefin polyannulation. By this strategy, compound 96, containing the tetracyclic core of scalarenedial, was constructed by exposure of the acyclic epoxy triene precursor 95 to MeAlCl2-promoted cyclization reaction conditions (Scheme 8.25) [45]. 

Recently Johnson and co-workers (84) have taken advantage of triplebond participation in biogeneticlike olefinic cyclizations. Treatment of trienynol 91 with 2% by weight trifluoroacetic acid at -70°C in methylene chloride gave largely the tricyclic triene 92 as product. Similarly, trienynol 93 underwent cyclization under the same conditions to give tricyclic product 94. 

Scheme 10.1 gives some representative examples of laboratory syntheses involving polyene cyclization. The cyclization in Entry 1 is done in anhydrous formic acid and involves the formation of a symmetric tertiary allylic carbocation. The cyclization forms a six-membered ring by attack at the terminal carbon of the vinyl group. The bicyclic cation is captured as the formate ester. Entry 2 also involves initiation by a symmetric allylic cation. In this case, the triene unit cyclizes to a tricyclic ring system. Entry 3 results in the formation of the steroidal skeleton with termination by capture of the alkynyl group and formation of a ketone. The cyclization in Entry 4 is initiated by epoxide opening. 

The reductive coupling/silylation reaction was extended to more complicated polyenes, such as the triene-substituted cyclopentanol 73, which cyclizes to provide 74 with a 72% yield and 6 1 dr after oxidation (Eq. 10) [44], The reaction is chemoselective the initial insertion occurs into the allyl substituent, which then inserts into the less hindered of the two remaining olefins, leaving the most hindered alkene unreacted. 

In intramolecular Diels-Alder reactions, two rings are formed in one step. The reaction has been used to synthesize a number of interesting ring systems.29 The intramolecular cyclization of ( )-l-nitrodeca-l,6,8-triene at 80 °C affords an endo cycloadduct with the tram ring fusion preferentially, as shown in Eq. 8.18. In contrast, (Z)-nitroalkenes produce a nearly 1 1 mixture of cis- and tra/w-fused cycloadducts.30... 

It will be clear from the results so far presented that both C5 and C dehydrocyclization products can be formed, with aromatization proceeding (one would expect) by further dehydrogenation of the initially formed C6 ring-closure species. There is another pathway for the production of aromatics based upon cyclization of a linear triene (133), but this is of relatively small importance, and is only significant at all at quite high temperatures and low hydrogen partial pressures. 

In an interesting illustration of these reactions, the two disymmetric trienes (+)-33a and (—)-33b were found to preserve their chirality upon photolysis at 193 K and provide cyclohexadienes 34a and 34b, respectively (Scheme 8)18. Upon warming above 205 K, however, they lose their chiral integrity by competitive disrotatory cyclization to the achiral dienes 35a and 35b. The thermal disrotatory closure to the cis-fused ring isomer is generally found to be extremely facile in these systems. 

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