Julia-Lythgoe olefination, carbonyl

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 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. 

Satoh, T., Hanaki, N., Yamada, N., Asano, T. A Sulfoxide Version of the Julia-Lythgoe Olefination A New Method for the Synthesis of Olefins from Carbonyl Compounds and Sulfoxides with Carbon-Carbon Coupling. Tetrahedron 2000, 56, 6223-6234. 

Among the different methods for the formation of C-C double bonds, the reductive elimination of (3-functionalized (mainly P-hydroxy or (3-carboxy) sulfones, is one of the most widely used ones in organic synthesis. The reductive elimination of (3-hydroxy sulfones and derivatives is the so-called Julia,94 or Julia-Lythgoe olefination reaction (Eq. 2). It usually involves a condensation between the anion of an alkyl sulfone and a carbonyl compound to afford a (3-hydroxy sulfone (Eq. 47). The metal alkoxide intermediate is typically transformed in situ into a carboxylic or sulfonic ester derivative, which is then reduced... 

Sylvestre Julia and co-workers discoveried in 1991 a direct synthesis of olefins by reaction of carbonyl compounds with lithio derivatives of 2-[alkyl- or (2 -alkenyl)- or benzyl-sulfonylj-benzothiazoles (BT, 5). Since the initial study of the reaction of metallated BT sulfone 5 with carbonyl compounds, the versatility of these derivatives has been fully demonstrated through their application in the total synthesis of a large number of nature products. Kocienski and co-workers found in 1998 that l-phenyl-17/-tetrazol-5-yl sulfone (PT, 6) is a better olefination partner comparing to BT sulfones. This allowed the one-port Julia-Lythgoe olefination to be employed more efficiently and broadly, especially in the synthesis of nature products. 

The sulfone is a versatile functional group comparable to the carbonyl functionality in its ability to activate molecules for further bond construction, the main difference between these two groups being that the sulfone is usually removed once the synthetic objective is achieved. The removal most commonly involves a reductive desulfonylation process with either replacement of the sulfone by hydrogen (Eq. 1), or a process that results in the formation of a carbon-carbon multiple bond when a P-functionalized sulfone, for example a (3-hydroxy or (3-alkoxy sulfone, is employed (Eq. 2). These types of reactions are the Julia-Lythgoe or Julia-Paris-Kocienski olefination processes. Alkylative desulfonylation (substitution of the sulfone by an alkyl group, Eq. 3), oxidative desulfonylation (Eq. 4), and substitution of the sulfone by a nucleophile (nucleophilic displacement, Eq. 5) are also known. Finally, p-eliminations (Eq. 6) or sulfur dioxide extrusion processes (Eqs. 7, 8 and 9) have become very popular for the... 

The temporary presence of a carbon-carbon double bond can be advantageous for creating branches in a molecular skeleton by bond formation. This functionality can be obtained not only by olefin metathesis, but also by any carbonyl olefination reaction (Wittig [24], Homer-Wadsworth-Emmons [25], Peterson, or Julia-Lythgoe [9]) (Scheme 3.14). 

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