Asymmetric total syntheses of 3‐oxacarbacyclin (4) and 3‐oxaisocarbacyclin (5) have been achieved by a new and common route. The key step of these syntheses is an enantioselective deprotonation of the prochiral ketone 25 with lithium (R,R)‐bis(phenylethyl)amide (12) in the presence of LiCl. Treatment of the thus formed enolate 26 with ClSiEt3 gave the enol ether 27 of 92% ee in 94% yield. Deprotonation of the analogous prochiral ketone 9 with 12 in the presence of LiCl followed by reaction of the enolate 13 with ClSiEt3 led to isolation of the silyl enol ether 8b of 92% ee in 95% yield. A study of the deprotonation of 9 with the chiral lithium amides 14−19 showed that 12 in combination with LiCl is the optimal base in terms of enantioselectivity and accessibility. The ω‐side chain in 4 and 5 was established by a Mukaiyama reaction of 27 with the unsaturated aldehyde 28, leading to ketone 39 of 90% de, in combination with a stereoselective Pd‐catalyzed allylic rearrangement of acetate 47 to the isomeric acetate 48 and a Mitsunobu reaction of the allylic alcohol 49. The key step in the construction of the α‐side chain in 4 is a Horner‐Wadsworth‐Emmons reaction of ketone 7c with the 8‐phenylnormenthol‐containing phosphonoacetate 56 which gave ester 60 of 90% de. Ester 60 was obtained diastereomerically pure by chromatography in 72% yield from 7c. Reduction of 60 furnished the allylic alcohol 62 which was converted to 4 in a standard fashion. It is at the stage of the α,β‐unsaturated ester 60 where divergence into synthesis of 5 was made. Selective isomerization of 60 to the β,γ‐unsaturated ester 66 of 97% ie in 91% yield was accomplished by deprotonation of 60 with 12 to enolate 65 and its subsequent regioselective protonation. By a similar reaction sequence the isomeric α,β‐unsaturated ester 61 was converted to the ß,γ‐unsaturated ester 69 of 97% ie in 88% yield. Reduction of 66 afforded the homoallylic alcohol 71 which was converted to 5 in a standard fashion.

hormones hormones U 1000 31 -249 Asymmetric Synthesis of 3-Oxacarbacyclin and 3-Oxaisocarbacyclin by a Common Enantioselective Deprotonation Based Route. -A new asymmetric synthesis of title compounds (XI) and (XIII), which are of medicinal interest, is presented. Key step is an enantioselective deprotonation of the prochiral ketone (I) with Li (R,R)-bis(phenylethyl)amide to the enol ether (III). -(VAULONT, I.; GAIS, H.-J.; REUTER, N.; SCHMITZ, E.; OSSENKAMP, R. K. L.; Eur.

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Erlei, Leschke und Sauerland Neue Institutionenökonomik