Julia-Lythgoe-Kocienski olefin synthesis

Lythgoe, Kocienski and their coworkers investigated the scope, stereochemistry and mechanism of the classical Julia olefination (also called the Juha-Lythgoe olefination) and paved the way for its broad application in target-oriented synthesis [87-90]. The bias towards fi-olefins, with the isomer ratio being typically in the range 7/3 to 9/1 for primary unhindered sulfones and aldehydes, marks a distinctive stereochemical feature of the reaction. 

Julia, M. Paris, J. M. Syntheses a L aide de Sulfones. V. Methode de Syntheses Generale de Doubles Liasons Tetrahedron Lett. 1973, 15, 4833-4836. Kocienski, P. J. Lythgoe, B. Ruston, S. Scope and Stereochemistry of an Olefin Synthesis from -Hydroxy-Sulfones /. Chem. Soc., Perkin Trans. 1 1978, 829-834. 

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 Julia-Lythgoe olefination and Kocienski modification have applied broadly in the synthesis of nature products. Isoprostane of A2 and h are isomeric of the cyclopentenone prostaglandins A2 and J2, respectively, which are reported to exert unique biological effects. Prostaglandins of A2 and J2 series have been reported to be active against a wide variety of DNA and RNA viruses, including HIV-1 and influenza virus. They also possess a potent anti-inflammatory activity due to the inhibition and modification of the subunit IKKP of the enzyme IA B kinase. Zanoni and co-workers reported the first total synthesis of A2 Isoprostane 101 employed a stereoselective Julia-Lythgoe olefination in the formation of C 13 14 double bond. The intermediate 99, obtained in 87% yield by addition of sulfone 97 to aldehyde 98, was reduced by Na(Hg) to alkene 100 in 81% yield. 

Hennoxazole A displays potency against Herpes Simplex virus type 1 and peripheral analgesic activity comparable to that of indomethacin. Williams and co-workers reported a total synthesis of (-)-hennoxazole A 141. The Kocienski modification of the Julia-Lythgoe olefination was very successfully employed in the formation of Cn-Cis alkene in 85% yield with excellent iJ-selectivity E/Z = 91 9) by reacting sulfone 140 with aldehyde 139. Hydrolysis of the C4 pivaloate ester (LiOH in aqueous THF/MeOH) provided synthetic hennoxazole A (141) in 72% yield. 

Marc Julia and Paris invented this methodology for the preparation of E)-olefin in the synthesis of Liaisons in 1973. The Julia coupling was applied to the synthesis of mono-, di- and tetra-substituted alkenes in the original communication. Kocienski and Lythgoe first demonstrated the trans... 

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