Prostaglandins and congeners VIII. An improved procedure for the conjugate addition of 3-oxy-E-1-alkenyl ligands via lithium alanate reagents. 11-deoxyprostaglandin E1 analogues
✍ Scribed by Karel F. Bernady; John F. Poletto; Martin J. Weiss
- Publisher
- Elsevier Science
- Year
- 1975
- Tongue
- French
- Weight
- 191 KB
- Volume
- 16
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
Recent communications from these laboratories have described a new and useful procedure for the synthesis of prostaglandins based upon the conjugate addition to cyclopentenones of E-lalkenyl ligands from lithium E-1-alkenyltrialkylalanate reagents.* The preparation of these alanate reagents requires diisobutylaluminum hydride reduction of terminal acetylenes. This reaction is disadvantageous with propargylic ethers, for these may not necessarily undergo the expected cis-wise hydroalumination 2b -and furthermore may suffer reductive cleavage of the carbonoxygen bonds. We now wish to report an improved alanate procedure for the 1,4-transfer of 3-oxy-E-1-alkenyl ligands, which eliminates the preparation of the alanate reagents via hydroalumination of propargylic ethers. 3-Oxy-E-1-alkenyllithium reagents may be obtained almost quantitatively by alkyllithiumalkenyl iodide exchange reactions. 3 We have found that the ate complexes formed by treatment of these alkenyllithiums with trialkylaluminums also conjugatively transfer the alkenyl ligands to cyclopentenones in good yield. Accordingly, I-iodo-E-1-octen-3-01 (1),3 protected as the panisyldiphenylmethyl ether 2, was metalated (toluene. 1 g/ml) with 1 equivalent of n-butyllithium in hexane (-40°, 2 hr) to yield octenyllithium 3. Addition at -78' of 1 equivalent of trimethylaluminum in heptane and allowing the mixture to warm to -10' ('Lo.5 hr) afforded the lithium alanate reagent a. To this reagent at -40' was added 1 equivalent of cyclopentenone z4 in ether (ether/ hydrocarbon -l/l, v/v) and the *-phase mixture was stirred at ambient temperatures for 16 hr. Protolytic work-up of the resulting single phase, followed by detritylation (80% acetic acid, 80°, 0.5 hr)5 and chromatography gave (71%) the methyl esters of dZ-11-deoxy-PGE, (16) and its C-15 epimer (17) in a ratio of 44:56, respectively.