Triene, skipped

By substituting SIPr for an N-alkyl-substituted NHC ligand (IfBu), the skipped-triene product (2) could be prepared selectively from cyclopropylen-yne substrates, regardless of substituent size (e.g., R) (Eq. 3) [11]. Thus, skipped-triene products were formed exclusively under mild conditions (room temperature, 2 h). 

The presence of a discrete organometallic species as well as the stereochemistry of the metalated diene were first checked by iodinolysis and bromolysis,but the corresponding iodo- and bromodienes were found to be unstable and rapidly isomerized to a mixture of E and Z isomers. Thus, in order to have a better picture of the stereochemical outcome of the process, the crude reaction mixture was treated with AT-chlorosuccinimide (Scheme 37), and the corresponding chlorodiene 103 was isolated in 60% yield with an isomeric ratio >98 2. As alternative solution, the stereochemistry of the reaction was also determined by addition of allyl chloride, in the presence of a catalytic amount of copper salt, to the dienyl zirconocene derivative [74]. Skipped triene 104 was... 

Homoconjugated or skipped trienes are vital components of natural products such as fatty acids, leucotrienes and insect pheromones. Pohnert and Boland have reported a detailed discussion of the synthesis of these molecules using a one-pot Wittig approach which employs bis(ylides) (77), (78) and (79) as key building blocks.New one-pot Wittig procedures have also been developed for the synthesis of alkynes and bromoalkynes (Scheme 13) and iodoalkynes (Scheme 14). The latter process utilises diiodomethyltriphenyl-phosphorane (80), which is generated in situ from triphenylphosphine, iodoform and potassium butoxide. 

The skipped di- or triynes are reduced to skipped (Z,Z)-diencs or (Z,Z,Z)-trienes by partial reduction with NaBH4/Ni(OAc)2 4H20 (equation 111). 

Conjugated or skipped dienes and trienes undergo ionization with alkali amides in liquid ammonia. In the cases of allylbenzene, heptatriene, indene, and cyclopentadiene, the equilibrium RH + MNH2 RM +NH3 is probably completely on the right side (with M = Na or K), but the thermodynamic acidities of cyclohexadiene and pentadiene are probably very close to that of ammonia, so that metallation with alkali amides (even potassium amide) may be incomplete. 

The synthesis of the skipped triene-oxazole fragment 1417 began with (Z)-2-butene-l,4-diol, which was converted to the unsaturated ester 1414 in three... 

The C(14)-C(25)-skipped trienoic acid 1432 was prepared from (5)-3-hydroxy-2-methylpropionate in 12 steps and 8% overall yield (Scheme 1.367). Coupling 1432 with L-serine methyl ester yielded the (3-hydroxyamide 1433. Sequential cyclization of 1433 with Deoxo-fluor to an oxazoline (not shown) and oxidation with CBrCla/DBU then produced the desired skipped triene-oxazole fragment 1417 in 73% yield. 

The plan was to elaborate the pyran moiety throu the aldehyde while the skipped triene would be elaborated through the protected hydroxypropyl side chain. 

The successful implementation of this strategy is shown in Scheme 1.370. The optically pure stannane 1441 was transmetalated in situ with 1442, preparing a borane reagent that condensed with 1440. After methylation, 1443 was isolated in excellent yield with 10.5 1 diastereoselection. At this point, 1443 was elaborated to incoprorate the pyran moiety (five steps), and the side chain was converted to an aldehyde (two steps). Overall, this reaction sequence to 1444 was accomplished in 46% yield. The skipped triene fragment was then incorporated via the anion of sidfone 1445. Saponification of the pivalate ester then completed the synthesis of 1191a. 

Coupling on a polymeric support can of course readily be applied to library building by combinatorial techniques. Several groups have reported work of this type thus Havranek and Dvofak [69] have carried out repeated coupling of 3-substituted 3-(tributylstannyl)allyl alcohols with substrates linked to a TentaGel S OH resin to obtain a 21 x 21 library of skipped dienes and a 21 x 21 x 21 library of skipped trienes. 

In their efforts to prepare a [D4]-labeled p4t-neuroprostane, the Galano group carried out partial reduction of the skipped diyne substrate in order to access the Z,Z,Z-triene moiety of the final product (Fig. 12) [34]. While Lindlar s catalyst provided a mixture of mono-reduction of the less hindered alkyne (with the ethyl substituent), the desired triene as well as over-reduced diene product, P-2 nickel yielded a much cleaner conversion to the desired product with 98% purity. The product was then transformed into the target molecule by a sequence of TBAF deprotection of the TBS ether and saponification. 

---