Of Julia olefination

Isomerization of allylic sulfones and reduction of conjugated double bonds (Eq. 62), are possible disadvantages of the use of Mg as an electron-transfer agent.117 The occurrence of Julia olefination of 1,2-disulfone derivatives is another important drawback when performing reductive desulfonylation on these kinds of substrates (Eq. 63).118... 

Bromomethyl)- or (hydroxymethyl)cycIopropane derivatives undergo acid-catalyzed homoallyiic rearrangements to yield trans-olefins (J.P. McCormick, 1975 S.F. Brady, 1968 M. Julia, 1974). This rearrangement is the basis of Julia s terpene synthesis (see. p. 70). 

A second paper161 describes the use of the same base in either THF or t-butanol for the elimination of a-acetoxy phenyl sulphones as outlined in equation (68), in essence a reaction sequence very similar to the Julia olefin synthesis (Section III.B.3) except in the method by which the sulphonyl group is finally removed. 

This section deals with reactions that correspond to Pathway C, defined earlier (p. 64), that lead to formation of alkenes. The reactions discussed include those of phosphorus-stabilized nucleophiles (Wittig and related reactions), a a-silyl (Peterson reaction) and a-sulfonyl (Julia olefination) with aldehydes and ketones. These important rections can be used to convert a carbonyl group to an alkene by reaction with a carbon nucleophile. In each case, the addition step is followed by an elimination. 

The Julia olefination involves the addition of a sulfonyl-stabilized carbanion to a carbonyl compound, followed by elimination to form an alkene.277 In the initial versions of the reaction, the elimination was done under reductive conditions. More recently, a modified version that avoids this step was developed. The former version is sometimes referred to as the Julia-Lythgoe olefination, whereas the latter is called the Julia-Kocienski olefination. In the reductive variant, the adduct is usually acylated and then treated with a reducing agent, such as sodium amalgam or samarium diiodide.278... 

Scheme 2.20 gives some examples of the application of the Julia olefination in synthesis. Entry 1 demonstrates the reductive elimination conditions. This reaction gave a good E.Z ratio under the conditions shown. Entry 2 is an example of the use of the modified reaction that gave a good E.Z ratio in the synthesis of vinyl chlorides. Entry 3 uses the tetrazole version of the reaction in the synthesis of a long-chain ester. Entries 4 to 7 illustrate the use of modified conditions for the synthesis of polyfunctional molecules. 

Chapters 1 and 2 focus on enolates and other carbon nucleophiles in synthesis. Chapter 1 discusses enolate formation and alkylation. Chapter 2 broadens the discussion to other carbon nucleophiles in the context of the generalized aldol reaction, which includes the Wittig, Peterson, and Julia olefination reactions. The chapter and considers the stereochemistry of the aldol reaction in some detail, including the use of chiral auxiliaries and enantioselective catalysts. 

There are several new methodologies based on the Julia olefination reaction. For example, 2-(benzo[t/Jthiazol-2-ylsulfonyl)-j -methoxy-i -methylacetamide 178, prepared in two steps from 2-chloro-iV-methoxy-jV-methylacetamide, reacts with a variety of aldehydes in the presence of sodium hydride to furnish the ajl-unsaturated Weinreb amides 179 <06EJOC2851>. An efficient synthesis of fluorinated olefins 182 features the Julia olefination of aldehydes or ketones with a-fluoro l,3-benzothiazol-2-yl sulfones 181, readily available from l,3-benzothiazol-2-yl sulfones 180 via electrophilic fluorination <06OL1553>. A similar strategy has been applied to the synthesis of a-fluoro acrylates 185 <06OL4457>. 

Conjugated C-l glycals have also been prepared from C-glycosylidene vinyl sulfones by means of a modified Julia olefination (Scheme 12e).68... 

C. Charrier, L. Ettouati, J. Paris, New application of the Julia olefination for the synthesis of Tyr-Gly -alkene and carba isostere pseudopeptides. Tetrahedron Lett. 40 (1999) 5705-5707. 

Sulfonylation of aromatic hydrocarbons in the presence of a Lewis acid and the reaction of sodium benzenesulfinate with alkyl halides proved to be particularly easy and useful to prepare starting materials for the Julia olefination procedure (see Section 4.3.2). 

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

Trost used the dihydroxylation methodology extensively in the total synthesis of (+)-parvi-florin (68) [96]. Both bistetrahydrofuran elements were prepared from 8, tn-dienyl alcohol 71. To avoid overoxidation the reaction was stopped before complete conversion, giving triol 72 with 94% ee in 71 % yield. Protection as the acetonide afforded 73 and subsequent hydrogenation furnished saturated alcohol 74. The construction of 75 was accomplished by Julia olefination using derivatives of 73 and 74. Diene 75 was thenregioselectively dihydroxylated at the internal... 

Cyclopropane compounds containing the olefin isostere replacement for the amide bond were prepared using Julia olefination chemistry. Aldehydes 39 and 40 were obtained by LAAIH4 reduction of the chiral w-butyl esters of 32 and 33, respectively, followed by swera oxidation of the corresponding alcohols (Figure 22). Condensation of the (S)-N-BOC-cyclohexylalanine sulfone 41 with aldehyde 39 gave after treatment with 2% Na(Hg) and deprotection, the trans and cis olefin-amines... 

The synthesis of cyclopropyl compounds containing the olefin replacement for the amide bond but without the additional primary chiral amino substituent were prepared by modified Julia olefination procedures. Addition of the benzothiazole sulfone 44 to aldehyde 39 gave trityl protected olefins in a 1 1 ratio. These... 

A disadvantage of the Julia Olefination is its low tolerance for reducible functional groups. The ( -selectivity is generally good to very good for alkenes with a low degree of substitution, while the selectivity improves as a function of increased branching in the substitutents. 

The Modified Julia Olefination (or Julia-Kocienski Olefmation) enables the preparation of alkenes from benzothiazol-2-yl sulfones and aldehydes in a single step ... 

The Julia-Kochienski Olefination - a further refinement of the Modified Julia Olefination - offers very good E-selectivity. 

In contrast to the classical Julia Olefination, the Modified Julia Olefination offers the possibility of saving one or two synthesis steps. In addition, there are fewer problems with scale-up than with the classical variant. The /Z-selectivity can be controlled by varying the sulfonyl group, solvent and base. 

Preparative methods and chemical properties of tetrazole-5-thiones (tetrazole-5-thiols) have been summarized in a review <2004RJ0447>. The most significant results in this field were obtained in the last decade while studying the alkylation of tetrazole-5-ylthiones (tetrazole-5-ylthiols), and the oxidation of 1-substituted 5-alkylsulfatetrazoles to the corresponding sulfinyl and sulfonyl derivatives. Special attention should be paid to the Kocienski-modified Julia olefination based on the application of 5-alkylsulfonyltetrazoles to the activation of chemical reactions. 

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... 

If one now considers what would probably be needed in the synthetic direction once aldehyde 5 had been reached, a -selective Evans asymmetric aldol reaction11 with boron enolate 6 could potentially set the C(21) and C(22) stereocentres in 3. All that would be required subsequently would be product liberation from the auxiliary by reduction, and oxidation at C(20). With compound 3 in hand the stage would then be set for implementation of the second Julia olefination tactic. 

P. R. Blakemore, The Modified Julia Olefination Alkene Synthesis via the Condensation of Metallated Heteroarylalkylsulfones with Carbonyl Compounds, J. Chem. Soc. Perkin Trans. 12002, 2563—2585. 

The fact that the Julia-Lythgoe olefination requires more than one step to prepare alkenes has generally been accepted as an inconvenient and inevitable part of the procedure developed by Marc Julia and Basil Lythgoe. This flaw kept nagging at Marc Julia s brother Sylvestre, who would not rest until he had found the one-step (Sylvestre) Julia olefination. The (Sylvestre) Julia-Kocienski olefination has become the state-of-the-art-variant of this olefination (Figure 11.23). It may be applied to any kind of aldehyde. 

The Julia olefin synthesis consists of the reaction of a sulfonyl anion with an aldehyde or ketone. The resulting alcohol is usually acetylated and the olefin formed by aluminum-amalgam reduction. The yield of / -hydroxysulfone is usually good, but the subsequent reductive elimination is more... 

Isopropyl anisole (171) was converted to bromide (172) by metalation, formylation and bromination. Alkylation with cyclopropyl ketoester produced (173) whose transformation to alcohol (174) was achieved by saponification, decarboxylation and reduction.. Its conversion to homoallylic bromide (175) was accomplished by the method of Julia et al. [56]. Alkylation of ethyl acetoacetate with bromide (175) furnished p-ketoester (176). It was subjected to cyclization with stannic chloride in dichloromethane. The resulting tricyclic alcohol provided the olefinic ester (177) by treatment with mesylchloride and triethylamine. Epoxidation followed by elimination led to the previously reported intermediate (146) whose conversion to triptolide (149) has already been described. 

Fig. 4.37. Julia-Lythgoe synthesis of tram-olefins involving a HetVHet2 elimination.

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