Alkenes 1,2-disubstituted, reductive elimination

In this chapter we deal with the tegio- and stereo-controlled synthesis of alkenes by reductive elimination of 1,2-disubstituted alkanes. Where appropriate the related 1,4-elimination reactions leading to conjugated dienes will also be considered. The principal criterion for inclusion here is synthetic utility, and reactions such as the Julia alkenation are given prominence because they incorporate a reductive elimination as a key step in a sequence which is connective. Consequently such reductive eliminations should not be considered in isolation, but as an integral part of a sequence which achieves regio- and stereo-con-... 

Alkene synthesis.9 The key step in the Julia synthesis of alkenes (11, 473-475) involves reductive elimination of a P-hydroxy sulfone with sodium amalgam. A recent modification involves elimination of a p-hydroxy imidazolyl sulfone with Sml2 (equation I).1 Both syntheses are particularly useful for preparation of disubstituted alkenes and conjugated dienes and trienes. Both methods of elimination favor formation of (E)-alkenes. In a direct comparison, a higher yield was obtained with Sml2 than with Na(Hg). 

The first step in this multistage reaction is the nucleophilic addition of sulfone anion 28 to aldehyde 8 (Scheme 14.6). This produces a p-alkoxysulfone intermediate 29 which is trapped with acetic anhydride. The resulting P acetoxysulfone mixture 22 is then subjected to a reductive elimination with Na/Hg amalgam to obtain alkene 23. The tendency of Julia-Lythgoe-Kocienski olefinations to provide ( )-1,2-disubstituted alkenes can be rationalised if one assumes that an a-acyloxy anion is formed in the reduction step, and that this anion is sufficiently long-lived to allow the lowest energy conformation to be adopted. Clearly, this will... 

We and others recently reported the metal-catalyzed addition of diboron compounds to alkenes and alkynes.15,16 Subsequent work has improved the catalysts and extended the scope of the substrate to include disubstituted alkenes, enynes, and dienes.17 Stoichiometric reactivity studies support a mechanism which involves oxidative addition of the B-B bond to the metal center, followed by insertion of the substrate into the M-B bond, and product-forming B-C reductive elimination (Scheme l).18... 

Disubstituted alkenes can undergo reductive elimination to acetylenes 1,2-dia-cetoxy-l,2-diphenylethylene may thus be reduced to diphenylacetylene in DMF at a mercury cathode [87]. In more pro tic media the diphenylacetylene is further reduced. A similar... 

A study carried out by Kocienski and Lythgoe flrst demonstrated the trans selectivity of the Julia coupling process. The authors found the i uctive elimination could best be carried out with the acet-oxy or benzoyloxy sulfones. If the lithio sulfone derivative is used for addition to the carbonyl, the reaction can be worked up with acetic anhydride or benzoyl chloride to obtain the alkene precursor. In cases where enolization of the carbonyl is a complication, the magnesium derivative can frequently be used successfully. A modification of the reductive elimination was found to be most effective. Methanol, ethyl acetate/methanol or THF/methanol were the solvents of choice and a temperature of -20 C was effective at suppressing the undesired elimination of the acetoxy group to produce the vinyl sulfone. With these modifications of the original procedure, the ability of the reaction to produce dienes as well as rran.r-disubstituted alkenes was demonstrated, llie diastereoisomeric erythro- and threo-acetoxy sulfones could be separated and it was demonstrated that both isomers were converted to the rrans-alkene. It... 

The Julia olefination reaction is highly regioselective and ( )-stereoselective, providing a valuable alternative to the Schlosser reaction for making rrans -disubstituted olefins. The reaction involves condensation of a metalated alkyl phenyl sulfone with an aldehyde to yield a P-hydroxysulfone, which is then subjected to a reductive elimination to produce the alkene. There are limitations to the preparation of tri- and tetra-substituted alkenes via the sulfone route because the P-alkoxy sulfones derived from addition of the sulfone anion to ketones may be difficult to trap and isolate or they may revert back to their ketone and sulfone precursors. 

In the narrower context of simple functional group manipulation, reductive eliminations have proved valuable in the vicinal deoxygenation of cheap and readily available natural products such as carbohydrates to give synthetically useful fragments. However, comparatively few of the vast array of reductive eliminations recently reported were deemed worthy of inclusion because the reagents required were esoteric, expensive or obnoxious, or because the 1,2-disubstituted alkanes were themselves prepared from alkenes. Unless there are very pressing reasons, one cannot advocate the synthesis of alkenes from alkenes to travel in circles is the domain of astronomers not chemists ... 

The Julia reductive elimination is a good choice when trying to prepare mono-, 1,1-di- and E-l,2-disubstituted alkenes. This application has been demonstrated, for example, in the preparation of a key intermediate in the synthesis of calciferol (Eq. 167).305 The alternative Wittig olefination approach failed due to the difficulties encountered in the preparation of the corresponding sterically hindered phosphonium halide.305... 

The presence of the hydride acyl intermediate in decarbonylation suggests the possibility of alkene insertion into the metal hydride bond and reductive elimination of a ketone. This was first observed in the intramolecular hydroacylation of 2,3-disubstituted 4-pcntcnals using stoichiometric amounts of Wilkinson s catalyst or in the presence of tin(IV) chloride to give substituted cyclopentanones and stereoisomeric cyclopropanes as side products27. 

Synthetic applications that consist of metal catalyzed addition of X-X to carbon-carbon unsaturated substrates, generally alkynes, have been described for X = X = SR, SeR, TeR and X = SeR, X = PR2 as well as X = SR, X = BR2, SiR3 [201], These transformations generally involve oxidative addition of the X-X reactant to the metal center followed by insertion of the alkyne, into the M-X bond. Reductive elimination leads to the final disubstituted alkene, which shows cis stereochemistry. 

A detailed investigation of the scope and stereochemistry of the reductive elimination leading to 1,2-disubstituted alkenes revealed high trans stereoselectivity which is independent of the stereochemistry of the /3-acyloxy sulfone adducts. Furthermore, the stereoselectivity increases with increasing steric congestion about the nascent alkene and maximum yields and rate are observed for the formation of conjugated dienes and trienes. The Julia procedure has also been adapted to the synthesis of alkynes (eq 12). ... 

Enantioselective hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alky-lidene-substituted carbocycles and heterocycles [27 b, 41, 42]. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. For systems that embody 1,2-disubstituted alkenes, competitive /9-hydride elimination en route to products of cycloisomerization is observed. However, related enone-containing substrates cannot engage in /9-hydride elimination, and undergo reductive cyclization in good yield (Table 22.12). 

Reductive cleavage of epoxides is successful primarily for terminal epoxides 1,2-disubstituted epoxides give alkenes by elimination of Li20, unless they are cyclic, in which case the secondary organolithium may be trapped with stereoselectivity at the former C-0 bond ... 

The relative stereochemistry of the newly formed stereogenic centers attained in the aminometa-lation reaction of 1,2-disubstituted alkenes is lost if the / -aminoalkylpalladium complex is allowed to undergo /J-hydride elimination to give enamines, or if a successive reduction step is performed, unless a stereocenter is initially present in the alkene or in the amine. However, the C —Pd bond can be functionalized to achieve overall oxyamination, diamination, aziridination, aminocarbonylation, and carboamination reactions13,14. 

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