Julia olefin synthesis

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. 

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

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... 

The Julia olefin synthesis is rather like the Wittig reaction with a sulfone instead of a phosphonium salt but with one other important difference the elimination step is stereoselective and both dia-stereoisomers of the intermediate can give the same isomer of the alkene. Treatment of the sulfone 147 with a strong base gives the anion 148 (or a metal derivative) that combines with an aldehyde to give a diastereomeric mixture of adducts 149. Elimination by various methods gives, in open chain compounds, mostly -150 but, in cyclic compounds, mostly the Z-alkene.29... 

The best version of the Julia olefin synthesis (so far) is probably that introduced by Kocienski.33 It uses /V-phenyl tetrazolyl sulfones 167 easily prepared from the available thiol 165 by a Mitsunobu reaction with a simple alcohol followed by oxidation. 

Application of the deoxygenation process to ff-hydroxysulfides or P-hydroxysulfones results in the clean formation of ra j-olefins through ji-elimination of a thiyl or sulfonyl radical [17]. This mild, radical version of the Julia olefin synthesis, initially described by Lythgoe and Waterhouse [17a], has been applied by two groups in the total synthesis of (+)-pseudomonic acid C. The transformation shown in Scheme 9 is taken from the synthesis by Williams and coworkers [17b]. 

The Johnson group also examined a synthesis that relied on the Julia olefin synthesis for construction of the central trisubstituted olefin. In this plan, 1 was to be prepared from an a-haloketone of type 39 via diastereoselective addition of a methyl group to the ketone, followed by a Williamson ether synthesis. Ketone 39 was to be prepared from 40 using an acetoacetic ester synthesis. Compound 40 was to be prepared from 41 using the Julia olefin synthesis. A make-or-break aspect of this plan was the stereochemical course of the Julia synthesis. Of course it was anticipated that the proper stereochemistry would result as will be seen shortly. 

Draw the conformation of 87 that is disposed to fragment to 72. (CJH-8) Oudine a synthesis of 93 using the Corey-Ratzenellenbogen synthesis to set stereochemistry. How might 93 be prepared using a Julia olefin synthesis. Comment on stereochemical aspects of the Julia route to 93. (CJH-9)... 

Kende AS, Mendoza JS. An improved variant of the Julia olefin synthesis-reductive elimination of (3-hydroxy imida-zolyl sulfones by samarium diiodide. Tetrahedron Lett. 1990 31(49) 7105-7108. 

Julia and Paris120 described an olefin synthesis, based on the use of a sulphonyl group which directs the formation of a carbon-carbon bond. Subsequent reductive elimination with sodium amalgam leads to the alkene, as outlined in equation (50). The reaction sequence is similar in principle to an olefin synthesis first developed by Cornforth121. The yields of all steps are generally above 80%. 

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>. 

The reductive elimination of /i-hydroxysulfones is the final step in the Julia-Lythgoe olefin synthesis.218 The /Lhydroxysulfones are normally obtained by an aldol addition. 

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. 

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... 

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... 

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. 

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. 

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

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