An asymmetric synthesis of isocarbacyclin (2) was achieved (97% ee), whose conversion to 8 has been already described, was isolated in 90% yield. The key step in the sequence from ketone 7 by the olefination-isomerization-coupling process with chiral sulfoximines. The vinylic sulfoximine 6 leading to the construction of the ω-side chain was the deprotonation of ketone 4b with a complex of lithium (R,R)-(Ն98% de) was prepared from ketone 7 and lithiosulfoximine 8 by an asymmetric olefination via an addition-elimination bis(α-phenylethyl)amide and lithium chloride, 29 • LiCl, which gave enolate 3. The use of ent-29 • LiCl in the process. Model experiments, aiming at a rationalization of the asymmetric induction in the elimination of βdeprotonation of 4b afforded the isomeric enolate 30.
Enolates 3 and 30 were trapped as the silyl ethers 31 (90% hydroxysulfoximines, with ketone 12 and lithiosulfoximine ent-8 revealed formation of the silyl ether 15 as an ie) and 32 (92% ie), respectively. The aldol reaction of 3 with (E)-octenal proceeded highly selective in regard to C-12 but intermediate which eliminated LiOSiMe 3 upon reaction with nBuLi under formation of (S,Z)-alkene 17 (Ն98% de).
unselective in regard to C-13 and gave aldols 34 (42%) and epi-34 (36%). It was at the stage of the aldol reaction of 3 Reaction of the C,O-dilithiosulfoximine 19 with ClSiMe 3 led to elimination of LiOSiMe 3 and also gave 17 (Ն98% de).
where the unwanted diastereomers 35 and epi-35, stemming from 30, could be separated. Reduction of ketones 34 and Methylation of 19, however, furnished the corresponding αmethyl-substituted β-hydroxysulfoximines, 20 and 21, in a epi-34 afforded diols 36 (Ն98% de) and 37 (93% de), respectively. The Pd-catalyzed rearrangement of the allylic ratio of 75:25. Isomerization of sulfoximine 6 gave the allylic sulfoximine 5 (96% de) whose absolute configuration was diacetates 39 and 41 was highly stereoselective (Ն98% de) but incomplete and led to formation of mixtures of 40 and 39 determined by X-ray structure analysis. Cross-coupling reaction of 5 with cuprate 23 delivered with high as well as of 42 and 41 in ratios of 84:16 and 86:14, respectively. A two-step oxidation of alcohol 43, regioselectivity alkene 25. A similar reaction of 5 with the organocopper reagent 26, which was prepared from contaminated by 5% of the isomeric alcohol stemming from acetate 39, via aldehyde 44 gave after purification by (benzyloxy)methylmagnesium chloride, in the presence of BF 3 • OEt 2 and halide afforded alkene 27. Ketone 28 is a crystallization isocarbacyclin (2) in 38% yield. Diol 45, having the undesired (15R) configuration, was selectively oxidized potential starting material for the asymmetric synthesis of 3oxaisocarbacyclin. Besides alkenes 25 and 27 sulfinamide 24 with dichlorodicyanobenzoquinone to enone 46 (81%).