Sulfones reductive elimination

A disadvantage of this procedure is that reductive cleavage of the epoxy sulfones leading to trisub-stituted alkenes, e.g. (95), is not stereoselective. However, formation of disubsituted alkenes follows the trends found in the standard Julia alkenation in that rrani-alkenes are favored (equation 24) and proximate branching increases the stereoselectivity (equation 25). Unlike the standard Julia alkenation, the stereochemistry of the epoxy sulfone reductive elimination depends on the stereochemistry of the precur-... 

SCHEME 22.3. Stereoselective sulfone reductive eliminations (NaHTe orSml2 ). 

Remarkable solvent effects on the selective bond cleavage are observed in the reductive elimination of cis-stilbene episulfone by complex metal hydrides. When diethyl ether or [bis(2-methoxyethyl)]ether is used as the solvent, dibenzyl sulfone is formed along with cis-stilbene. However, no dibenzyl sulfone is produced when cis-stilbene episulfone is treated with lithium aluminum hydride in tetrahydrofuran at room temperature (equation 42). Elimination of phenylsulfonyl group by tri-n-butyltin hydride proceeds by a radical chain mechanism (equations 43 and 44). 

The reductive elimination of a variety of )3-substituted sulfones for the preparation of di-and tri-substituted olefins (e.g. 75 to 76) and the use of allyl sulfones as synthetic equivalents of the allyl dianion CH=CH—CHj , has prompted considerable interest in the [1,3]rearrangements of allylic sulfones ". Kocienski has thus reported that while epoxidation of allylic sulfone 74 with MCPBA in CH2CI2 at room temperature afforded the expected product 75, epoxidation in the presence of two equivalents of NaHCOj afforded the isomeric j ,y-epoxysulfone 77. Similar results were obtained with other a-mono- or di-substituted sulfones. On the other hand, the reaction of y-substituted allylic sulfones results in the isomerization of the double bond, only. The following addition-elimination free radical chain mechanism has been suggested (equations 45, 46). In a closely related and simultaneously published investigation, Whitham and coworkers reported the 1,3-rearrangement of a number of acyclic and cyclic allylic p-tolyl sulfones on treatment with either benzoyl peroxide in CCI4 under reflux or with... 

There are a number of procedures for coupling of terminal alkynes with halides and sulfonates, a reaction that is known as the Sonogashira reaction.161 A combination of Pd(PPh3)4 and Cu(I) effects coupling of terminal alkynes with vinyl or aryl halides.162 The reaction can be carried out directly with the alkyne, using amines for deprotonation. The alkyne is presumably converted to the copper acetylide, and the halide reacts with Pd(0) by oxidative addition. Transfer of the acetylide group to Pd results in reductive elimination and formation of the observed product. 

The first step in the cycle, analogous to the cross-coupling reactions, is the oxidative addition of an aryl (vinyl) halide or sulfonate onto the low oxidation state metal, usually palladium(O). The second step is the coordination of the olefin followed by its insertion into the palladium-carbon bond (carbopalladation). In most cases palladium is preferentially attached to the sterically less hindered end of the carbon-carbon double bond. The product is released from the palladium in a / -hydrogen elimination and the active form of the catalyst is regenerated by the loss of HX in a reductive elimination step. To facilitate the process an equivalent amount of base is usually added to the reaction mixture. 

The presence of an NH group is essential, since the Boc-p-amino sulfone derived from Pro could only be coupled with lower yields (-20%). This method is also suitable for the preparation of pseudodipeptides having functionalized side chains such as those of Ser and AsnJ72l The p-oxo sulfone 51, which was obtained by reacting Boc-pAla-OMe with the dilithium anion of methyl phenyl sulfone, cleanly reacted with ethyl bromoacetate to give the p-oxo sulfone 52 (86%). The latter was reduced using LLAIH4, which on reductive elimination produced the over-reduced Boc-Alai)i(CH2—CH2]Gly-OMe isostere (80%). 

Another sulfone-based elimination of large applicability was proposed by Julia [418,419], Condensation of a metalled phenyl alkyl sulfone with a carbonyl compound, functionalization of the alkoxide and reductive elimination leads to an olefin. 

The reductive elimination of 0-hydroxyimidazoyl sulfones by samarium iodide was claimed to be an improved variation of the Julia olefin synthesis [421]. 

In contrast to a-(phenyl-A3-iodanyl) ketones, it is possible to isolate a-(phenyl-A3-iodanyl) sulfone 60 as a stable crystal [100]. The sulfone 60 undergoes substitutions with various nucleophiles with reductive elimination of iodobenzene. 

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). 

In the previous subsection, it was shown that the Ferrier reaction offers an opportunity to convert glycal derivatives into unsaturated sugar derivatives, which have an isolated double bond between C(2) and C(3). The Tipson-Cohcn reaction is another important reaction for the introduction of isolated double bonds.29 In this procedure, a cis or tram diols are converted into disulfonates (mesylates or tosylates) which are reductively eliminated with sodium iodide and zinc in refluxing DMF (Scheme 3.6a). In this reaction, the C(3) sulfonate is substituted by an iodide, which then is reductively removed by zinc with concomitant elimination of the second sulfonate moiety, introducing a double bond. Stereoelectronic effects make nucleophilic substitutions at C(3) more favourable than similar reactions at C(2) (see Section 3.2.3). Probably, the elimination proceeds through a boat conformation. In this case, the iodide and tosylate are in a syn relation. In most cases, E2 elimination proceeds via a transition state involving an anti orientation. Nevertheless, syn elimination becomes the dominant mode of reaction when structural features prohibit an anti orientation. 

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... 

The facility of arene reductive elimination underpins numerous C-C, C-O and C-N bond-forming reactions, which may be catalysed by late transition metals, in particular palladium (Figure 4.10). Although there are many variants, the general reaction scheme involves introduction of the aryl in electrophilic form via oxidative addition of an aryl halide (or sulfonate), substitution of the palladium halide by a nucleophile (which may also be carbon based) followed by reductive elimination. It is noteworthy that nucleophilic aromatic substitution in the absence of such catalysts can be difficult. 

The generally accepted mechanism for the amine arylation is shown in Scheme 1. The catalytic cycle begins with the oxidative addition of the aryl halide (or sulfonate) by Pd (0). The palladium (II) aryl amide can be formed either by direct displacement of the halide (or sulfonate) by the amide or via the intermediacy of a palladium (II) alkoxide [19]. Reductive elimination of the C-N bond results in the formation of the desired arylamine and regeneration of the Pd (0) catalyst [lie,20]. 

The Julia alkenation, also known as the Julia-Lythgoe alkenation is a reaction of phenyl sulfones 4.54 with aldehydes or ketones followed by reductive elimination with sodium amalgam to give alkenes. 

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