1.2.4- Trienes, diene syntheses

It is now principally important to consider trienes with the general formula MeCH=CH-CH= CH-CH2-CH2-CH2-CH=CHR. Such trienes contain moieties both of the diene and dienophile types within the framework of the same molecule. On initiation by the ArjN cation-radical, cycli-zation takes place. Tetrahydroindanes are formed. The trienes of R=PhS, p-MeOCgH4CH2, and H have been studied. The third triene, R=H, contains the dienophile fragment of lowered oxidizability it is not cyclized at all. The diene synthesis proceeds in the cases of the first two trienes only (Harirchian and Bauld 1987 see Scheme 7.23). 

Feast WJ, Hughes RR, Musgrave WKR (1977) Diels-Alder reactions of polyfluorocyclohexa-1,3-dienes. Part VIII. Reaction of tiifluoroacetonitiile with perfluorotricyclo[6,2,2,0 - ] dodeca-2,6,9-triene. A synthesis of perfluoro-3-methylisoquinoline. J Fluorine Chem 9 271-278... 

Jote 2. We have also carried out this synthesis in ethanol as a solvent but the results were not reproducible. Although a series of experiments with zinc powder from one flask gave reasonable results (50-78% yields), a new flask with the same batch number gave low yields of impure products. The main impurity was probably the non-conjugated diene, H2C=CH-CH2-CH=CH-CH3, possibly resulting from reduction of the 1,2,4-triene by the zinc. The... 

Conjugated dienes can be epoxidized to provide vinylepoxides. Cyclic substrates react with Katsuki s catalyst to give vinylepoxides with high ees and moderate yields [17], whereas Jacobsen s catalyst gives good yields but moderate enantiose-lectivities [18]. Acyclic substrates were found to isomerize upon epoxidation (Z, )-conjugated dienes reacted selectively at the (Z)-alkene to give trans-vinylepoxides (Scheme 9.4a) [19]. This feature was utilized in the formal synthesis of leuko-triene A4 methyl ester (Scheme 9.4b) [19]. 

The first example of successful diene-diene RCM to construct a macrocyclic conjugated triene was disclosed by Wang and Porco in the first total synthesis of oximidine II (258) [121]. Oximidine II belongs to the family of salicylate en-... 

The synthesis of fUido-tricyclo[4.4.0.02 5]deca-3,8-dien-7,10-dione and verification of its endo-configuration has been reported earlier.3 This adduet is a useful starting material for the syntheses of tetracyclo-[5.3.0.02 6.03 10]deca-4,8-diene,s tricyclo[4.4.0.02 5]deca-3,7,9-triene,6 cis, syn, cjs-tricyclo[5.3.0.02,6]deca-4,8-dien-3,10-dione,7 and 4-oxahexa-cyclo[5.4.0.02 6.03 10.05 9.08,11]undecane.a... 

The trans-cis isomerization process observed in the eudesmane/germacrane ring system has been utilized for the synthesis of the c/s-fused sesquiterpene occidentalol, 48a, and its 7-epi isomer, 48b (Scheme ll)22. Photolysis of the traws-fused diene 45 at —78°C afforded triene 46, which upon warming underwent disrotatory electrocyclization to give 47a and 47b as a 1 2 mixture of diastereomers. Apparently, the carboalkoxy group imparts... 

Suitably positioned vinyl halide can undergo Heck-type intramolecular coupling to generate dienes (equations 124 and 125)216,217. When one of the reacting partners in the Heck reaction is a diene, trienes are obtained (equation 126)218. Heck coupling of ally lie alcohols and alkenyl iodides has been employed for the synthesis of vitamin A and related compounds (equation 127)219,220. A similar double Heck reaction on a Cio-diiodide with a Cis-allylic alcohol leads to -carotene as a mixture of isomers (equation 128)209e. 

With the C12,C13 disconnection producing an effective solution to the synthesis of epothilone A (4), it would seem likely that the metathesis approach could be extended readily to the preparation of epothilone B (5). However, installation of the desired C12 methyl group requires ring-closure of a diene precursor in which one of the olefins is disubstituted. Recently, such reactions have been shown to be problematic for Grubbs initiator 3 but more successful with Schrock s molybdenum initiator 1 [19]. Consistent with these reports, Danishefsky demonstrated that triene 38 would not undergo RCM with 3, whereas 1 was effective in promoting the transformation of 38 into a 1 1 mixture of 39a and 39b in good yield [14b] (Scheme 8). 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Carboxylation of dienes and trienes, which takes place in a stepwise fashion, affords mono- or dicarboxylated products.146 Cobalt carbonyl,147 palladium chloride,148 149 and palladium complexes150 were used. 1,4 Addition to 1,3-butadiene gives the corresponding unsaturated tram ester (methyl trans-3-pentenoate) in the presence of [Co(CO)4]2 and a pyridine base.147 The second carboxylation step requires higher temperature than the first one to yield dimethyl adipate. In a direct synthesis (110°C, 500 atm, then 200°C, 530 atm) 51% selectivity was achieved.147... 

Various aspects of this reaction have been summarized by Kocienski.2 It is particularly useful for synthesis of disubstituted alkenes and conjugated dienes and trienes. It fails with some trisubstituted alkenes and most tetrasubstituted. alkenes because the precursors are unstable. One advantage of this route is that rra/is-alkenes are formed preferentially or exclusively. Yields are highest when the eliminated groups can adopt a /rons-coplanar arrangement. 

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