Julia olefination Kocienski modification

A stereoselective construction of the Z)-e/yr/tro-azidosphingosine characteristic trans double bond was accomplished by Panza and co-workers by condensation reaction between tetradecanol and a heterocyclic sulfone derived from diethyl Z)-tartrate, following the Kocienski modification of the Julia-Lythgoe olefination. Alcohol 71 was first converted into the 1-phenyl-l//-tetrazole-5-yl thioether under Mitsunobu conditions and then oxidized to 73 in 80% yields. A solution of sulfone 73 in DME at -55 "C was treated with KHMDS to give a stable anion of compound 73, which was then reacted with tetradecanal to give compound 74 in 53% yield. The compound 74 can be efficiently transformed into the target, 3-(9-(4-methoxybenzyl)-azidosphingosine, with reported procedure. 

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. 

In a pivotal modification of the direct olefination reaction Kocienski and his coworkers [10] showed that the use of l-phenyl-lff-tetrazol-5-yl sulfones, preferentially with NaHMDS or KHMDS as the base and DME as the solvent, provides olefins in excellent yields and stereoselectivity with respect to -isomers. The modified version of the direct olefination reaction has frequently been referred to as the Julia-Kocienski olefination reaction. 

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