Stereodefined double bonds

Lichtenhaler s synthesis of the (—)-ACRL toxin I shows good levels of stereocontrol except for the installation of one stereocentre, the C(5)-hydroxyl. Its longest linear sequence of only 20 steps, for installing six asymmetric centres and two stereodefined double bonds, corresponds to... 

Intermolecular trapping of this organosamarium with an appropriate electrophile produces branched cyclopentanol derivatives. In addition, the presence of intramolecular radical traps allows the rapid assembly of bicyclic ring systems with stereodefined double bonds, via an appropriate intramolecular cyclization. For example, reaction of iodopyranoside 82 with Sml2 in the presence of HMPA afforded bicyclic derivative 83 (Scheme 3.31) [67]. 

Use molecular models to check that only the Z double bond is formed. Stereoelec-tronically controlled fragmentations have often been used to provide stereodefined routes to large rings or unsaturated compounds. 

Open-chain SE2 reactions are special cases of electrophilic attack on a C=C double bond in the sense 5.132, with attack specifically at C-3, and followed by the loss of an electrofugal group from the stereogenic centre. The most studied of these are the electrophilic substitution reactions of stereodefined allylsilanes,... 

The hydroboration-coupling approach for the construction of carbon skeletons affords several advantages [139]. The high stereoselectivity of the hydroboration reaction provides a stereodefined alkyl center on boron. For instance, in the reaction shown in Scheme 2-49, the hydroboration occurs chemoselectively at the less hindered C(19)-C(20) double bond. In addition, the alkylboron group thus constructed can be readily cross-coupled with alkenyl or aryl halides under mild conditions. 

The Peterson olefination is a connective alkene synthesis and represents a useful alternative to the Wittig reaction. The precursors for the Peterson olefination are 3-hydroxy-alkyltrimethylsilanes which undergo P-elimination of trimethylsilanol under basic or acidic conditions to furnish stereodefined alkenes. This olefination method is especially valuable for the preparation of terminal and exo-cyc ic double bonds and for the methylenation of hindered ketones where the Wittig reaction is problematic. Also, the... 

Formation of carbon-carbon 7i-bonds elaboration of alkynes to stereodefined alkenes via reduction, current olefination reactions, and transposition of double bonds... 

Chiral sy -alk-l-ene-3,4-diols produced in this way embody, besides two stereodefined alcoholic centres, a carbon-carbon double bond amenable to further stereoselective functionalizations, thus opening entries to densely functionalized carbon chains, typically present in a plethora of naturally occurring compounds. 

When the triple bond is terminally substituted, 5-ejco-dig cyclization and subsequent H-abstraction generate a trisubstituted double bond. Malacria and co-workers have shown that the configuration of the double bond can be controlled by varying the nature of the terminal substituent, thus providing a novel entry into stereodefined trisubstituted double bonds [65], which are not always easy to access via more conventional protocols. 

Nonetheless, we decided to try to optimize the hydroxyl-directed hydroalu-mination [29] reaction as it provides an excellent vehicle to accomplish complete stereocontrol in the formation of the double bond, due to the formation of the relatively stable intermediate carboaluminate, which results from the regio and diastereo-selectivity of the addition reaction (The Jamison group [17] has elegantly demonstrated a complementary strategy where the resulting aluminate species is transmetallated to a Cu reagent and then functionalized via alkylation to afford stereodefined trisubstituted olefins.). Stereo-complementary results can be obtained if the alcohol function is protected. 

The synthesis of stereodefined substituted alkene is one of the major challenges in organic synthesis, as many naturally occurring compounds such as pheromones and hormones contain mono-, di-, or trisubstituted double bonds. In many cases a small amount of the wrong isomer acts an inhibitor of their biological activity. Thus, a highly stereospecific synthesis of such compounds is required. The organometallic compounds are such class of compounds that leads to the synthesis of desired molecules. 

The reaction is very useful in the stereodefined synthesis of 1,5-alkadienes. Consequently, the selective hydroboration of a terminal double bond of tri-ene, followed by coupling with ethyl-( )-2-bromocrotonoate in DMF using PdCl2(dppf) and KjPO affords the corresponding trienic ester in 60% yield. Similarly, coupling with (Z)-3-bromo-2-butanol tetrahydropyranyl ether affords a 67% yield of farnesol tetrahydropyranyl ether (Chart 31.2) [2]. 

The reaction is extended to the synthesis of arylacetylenes and stereodefined enynes. The reactions sequence involves the preparation of thermally stable lithium complexes from B-OMe-9-BBN and alkyllithium in THE at -78 C. These complexes undergo Pd-catalyzed Suzuki coupling to both aromatic and olefinic substrates to produce a variety of alkynyl derivatives and enynes, with complete retention of the double bond geometry (Eq. 31.4) [4a]. 

The metal-based preparations of conjugated dienes represent the majority of the strategies employed to attain stereoselectively 1,3-dienes connected to aryl and/or alkyl appendages. The starting material can be stereodefined when double bonds or enynes are engaged. When alkynes or allenols are employed, two double bonds are generated in a stereoselective manner. 

Yu et al. combined the Suzuki coupling with an alkyne insertion in aryl iodides and developed an efficient route to seven-membered rings with a stereodefined exocyclic double bond [43] (Scheme 6.25). Various aryl iodides and arylboronic acids bearing electron-donating or electron-withdrawing groups could be introduced efficiently to the palladium-promoted catalytic system. 

In 2003, Zhu and Zhang reported a palladium-catalyzed cyclization/arylation cascade reactions of enynes with arylboronic acids leading to cyclic products with a stereodefined exocyclic double bond [44] (Scheme 6.26). Several types of enynes can be anployed carbon, oxygen, and nitrogen tethers [Y=C(COjMe)j, O, Ts], and alkyl- and arylalkynes are well tolerated. The author proposed a plausible mechanism, probably involving a Jt-allylpalladium complex which is formed from the aUyUc halide, followed by insertion of the alkynes and Suzuki coupling reactions. 

Kitching and co-workers " " developed total syntheses of plakortones C, D, E, and F. Acquisition of plakortone D, the most effective activator of SR-Ca " -pumping ATPase, used stereodefined lactone cores that resulted from asymmetric dihydroxylation of protected homoallylic alcohol 67 (Scheme 15.18). A derived lactone aldehyde was then coupled with an independently generated, sulfone activated side chain unit 68. The 5,6- -double bond, carried through the sequence as a protected, stereodefined diol, was released there by stereospecific sy/j-elimination via an orthoester derivative. Racemic plakortone E was also acquired by using the Pd(II) induced sequence, but in this case, the required, complete acyclic system 69 was assembled first. 

Miscellaneous. An important method for the synthesis of stereodefined trisubstituted double bonds involves the treatment of cyclopropyl bromides with ZnBr2. The (E) isomer is obtained almost exclusively by this method (eq 23). ... 

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