Kocienski modified Julia olefination

Preparative methods and chemical properties of tetrazole-5-thiones (tetrazole-5-thiols) have been summarized in a review <2004RJ0447>. The most significant results in this field were obtained in the last decade while studying the alkylation of tetrazole-5-ylthiones (tetrazole-5-ylthiols), and the oxidation of 1-substituted 5-alkylsulfatetrazoles to the corresponding sulfinyl and sulfonyl derivatives. Special attention should be paid to the Kocienski-modified Julia olefination based on the application of 5-alkylsulfonyltetrazoles to the activation of chemical reactions. 

In the Kocienski-modified Julia olefination, replacement of the phenylsulfone moiety with a heteroarylsulfone such as the 1-phenyl-l/T-tetrazol-5-yl group (PT), shown below, profoundly alters the course of the Julia coupling. The olefin product is obtained in a one-pot procedure as opposed to the three-step protocol of the classical Julia olefination. ... 

Our spectroscopic data for (+)-lepadin F matched those reported by Carroll and coworkers [155] for the natural (+)-lepadin F and Blechert s synthetic sample [162], thereby allowing us to claim a completed total synthesis. Yet we believe there is a high margin of error in determining the C5 stereochemistry, since not only was the C5 stereocenter never defined in the isolation report, but also the C5 stereocenter is acyclic and highly insulated on the side chain. Consequentiy, we synthesized the C5 epimer of (+)-lepadin F commencing with advanced intermediate aldehyde 339 and sulfone (E)-340 in the requisite Kocienski-modified Julia olefination (Scheme 12.84) [166]. Spectroscopic comparisons of both H- and C-NMR data sets of our synthetic (+)-lepadin F and (+)-5 -epi-lepadin F with the natural (+)-lepadin F of Carroll and coworkers enabled us to confirm the correct relative stereochemistry at C5 in (+)-lepadin F as S. 

The Modified Julia Olefination (or Julia-Kocienski Olefmation) enables the preparation of alkenes from benzothiazol-2-yl sulfones and aldehydes in a single step ... 

The Julia-Kocienski olefination of heterocyclic sulfones and aldehydes, which is an alternative to the modified Julia olefination, forms alkenes with good -selectivity. First, sulfone 54 is deprotonated in the a-position to the sulfur by sodium hexamethyldisilazide (NaHMDS) and the sulfur-stabilized anion 55 then adds to the alde-... 

The architecturally novel macrolide (+)-zampanolide was synthesized in the laboratory of A.B. Smith. The C8-C9 ( )-olefin moiety was constructed using the Kocienski-modified Julia oleHnation. The required PT-sulfone was prepared from the corresponding primary alcohol via a two-step protocol employing sequential Mitsunobu reaction and sulfide-sulfone oxidation. The primary alcohol and two equivalents of 1-phenyl-1 H-tetrazolo-5-thiol was dissolved in anhydrous THF at 0 °C and treated sequentially with triphenylphosphine and DEAD. The desired tetrazolo sulfide was isolated in nearly quantitative yield. 

Kocienski, P. J., Bell, A., Blakemore, P. R. 1-tert-Butyl-1H-tetrazol-5-yl sulfones in the modified Julia olefination. Synlett 2000, 365-366. 

Spirotryprostatin A 142 and B 143 are two powerfully bioactive indole alkaloids. Both compounds inhibit the cell cycle in the G2/M phase, and 143 shows cytotoxic activity on the growth of human leukemia cell lines. Meyers and Carreira reported a total synthesis of 143. The Kocienski modified Julia olefmation was used in the formation of trisubstituted olefin without scrambling at Ci8. The alkene 146 was prepared in 78% yield by reacting sulfone 145 with aldehyde 144. The final product 143 was obtained by four-step reaction from the intermediate 146. 

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 S. Julia olefination reaction modified and optimized by P. Kocien-ski [10] became the premiere fragment linkage reaction in construction of functionally complex targets. It has frequently been referred to as the Julia-Kocienski reaction. 

In the asymmetric total synthesis of (-)-callystatin A by A.B. Smith and co-workers, two separate Julia olefinations were used to install two ( )-alkene moieties.The C6-C7 ( )-alkene was installed using the Kocienski-modified process in which the PT-sulfone was dissolved along with the a, 3-unsaturated aldehyde in DME and treated with NaHMDS in the presence of HMPA. The ( )-olefin was the only product but due to the relative instability of the starting PT-sulfone, the isolated yield of the product was only modest. 

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. 

---