Olefins Julia-Lythgoe olefination

Julia Olefination (Julia-Lythgoe Olefination) The Reaction ... 

Retrosynthetic addition of elements such as sulfur, selenium, phosphorous or boron may be required as part of a disconnective sequence, as in the Julia-Lythgoe E olefin transform as applied to 33. 

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... 

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. 

The Julia-Lythgoe olefination operates by addition of alkyl sulfone anions to carbonyl compounds and subsequent reductive deoxysulfonation (P. Kocienski, 1985). In comparison with the Wittig reaction, it has several advantages sulfones are often more readily available than phosphorus ylides, and it was often successful when the Wittig olefination failed. The elimination step yields exclusively or predominantly the more stable trans olefin stereoisomer. 

The Julia-Lythgoe-Kocienski olefination reaction7 between 5 and 8 to obtain alkene 23... 

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... 

Scheme 14.6 The Julia-Lythgoe-Kocienski olefination method.

Alkene-Forming Step of the Julia-Lythgoe Olefination... 

The last step of the Julia-Lythgoe olefination is an elimination, which is typically performed with sodium amalgam and starts with an Elcb elimination to give an alkenyl sulfone (mechanistic analysis Figure 4.40) with its reduction to the alkene following in situ. Both the related mechanism and an explanation of the resulting fraws-selectivity will be outlined later in Figure 17.85. 

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. 

Fig. 11.22. Julia-Lythgoe olefination of aldehydes to form trans-alkenes in two steps (1) addition of a lithium sulfone B <-> B1 to an aldehyde in-situ acetylation (2) reduction of the syir.cmti-diastereomeric mixture of the resulting sulfonylacetates C with sodium amalgam.

Marc) Julia-Lythgoe- and (Sylvestre) Julia-Kocienski Olefination... 

The Julia-Lythgoe olefination has already been addressed twice as an important C=C double bond-forming two- or three-step synthesis of trans-alkenes (trans-B in Figure 17.85). The step... 

Fig. 17.85. Mechanistic analysis of the second part of the reaction process where the treatment of the acetoxy sul-fones syn- and anti-A with sodium amalgam completes the Julia-Lythgoe olefination. Series of a first electron transfer (—> alkenyl phenylsulfone radical anion E), homolysis (—> alkenyl radical G + sodium benzene sulfinate), second electron transfer (—> alkenyl anion trans"-D) and in-situ protonation.

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