| Abstrakt: |
5-(2',6',6'-Trimethyl-1'-cyclohexen-1'-yl)-4-penten-2-yn-1-al has been prepared in a one-pot process starting from β-ionone in almost quantitative yield. Using 1,4-nucleophilic addition reactions, the corresponding 9-Cl, 9-Br, 9-I β-ionylideneacetaldehyde systems could be obtained in one step in quantitative yield as a mixture of (9Z) and (all-E) isomers. Even the corresponding fluoro derivative could be obtained in good yield as (9Z) and (all-E) isomers. In the case of a double bond having a halogen substituent, the IUPAC rules have the (E) nomenclature for a cis double bond and the (Z) for a trans double bond. Simple column chromatography gave the pure (9Z) and (all-E) form. Optimizing the Wadsworth−Emmons coupling gave the corresponding (all-E)- and (9Z)-retinonitriles in quantitative yield. Subsequent DIBAL-H reduction gave the corresponding retinals. For the preparation of the (11Z) isomers essential to vision, we found that Wadsworth−Emmons reactions with the diphenyl phosphonate group gave retinonitriles in quantitative yield, where the newly formed double bond is predominantly the (11Z) form (> 60%), together with the (9Z) isomer as minor component. The nitriles could be isolated in pure (9Z,11Z) and (9Z) forms by simple column chromatography. In the case of the (9Z,11Z)-9-demethyl-9-halo systems, a complication arose due to the unprecedented acid lability of these (9Z,11Z) aldehydes. By adjusting the DIBAL-H reduction workup procedure, these aldehydes are now available in pure form. We used this strategy to rationally synthesize (11Z)-retinal starting from β-cyclocitral as a first test for the generality of our new approach. β-Ionylideneacetaldehyde could be prepared in the (all-E) form in almost quantitative yield. Extending the conjugated chain of this molecule gave an almost quantitative yield of a mixture containing 80% (11Z)-retinal and 20% (all-E) as the minor component. Simple column chromatography gave pure (11Z)-retinal in 75% overall yield. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) |
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