4,5‐Didehydro‐9‐demethyl‐9‐halo‐5,6‐dihydroretinals and Their 9‐Cyclopropyl and 9‐Isopropyl Derivatives − Simple Preparation of α‐Ionone Derivatives and Pure (all‐E)‐, (9Z)‐ and (11Z)‐α‐Retinals

Abstract

Abstractα‐Ionone and several of its chemically modified derivatives have been prepared in high yield in full isomeric purity by a Wadsworth−Emmons procedure using imino‐phosphonate anion reagents. Starting from α‐ionone, 5‐(2′,6′,6′‐trimethylcyclo‐2′‐hexen‐1′‐yl)‐4‐penten‐2‐yn‐1‐al could be prepared in a high yielding one‐pot procedure. The corresponding (9‐Cl‐, 9‐Br‐ and 9‐I‐α‐ionylidene)acetaldehyde system could be obtained in one step in a quantitative mixture of (9Z) and (all‐E) isomers by 1,4‐nucleophilic addition reactions. The pure (all‐E) and (9Z) isomers could be separated by simple column chromatography. The corresponding [(9Z)‐ and (all‐E)‐9‐demethyl‐9‐fluoro‐α‐ionylidene]acetaldehydes could also be obtained in pure form by simple column chromatography. These α‐ionylidene systems could be easily converted either into the (all‐E)‐4,5‐didehydro‐9‐demethyl‐9‐halo‐5,6‐dihydroretinals or the corresponding (9Z) isomers in two steps. Similar mixtures of the corresponding (9Z,11Z)‐ and (9Z)‐nitriles could be obtained by normal chemistry. The (9Z,11Z) isomer is the main component of this mixture, and could be obtained in pure form. Subsequent reduction with DIBAL‐H and careful workup gave the pure (9Z,11Z)‐9‐haloretinals. These (9Z,11Z) isomers show a similar extreme acid sensitivity to the corresponding 9‐halo‐β‐retinals. α‐Retinal and its 9‐demethyl, 19,19‐ethano and 19,19‐dimethyl derivatives have been prepared in the (all‐E), (9Z), and (11Z) isomeric forms in a similar manner. The corresponding β‐retinal and its 9‐demethyl derivative in the various isomeric forms are known. In this paper the 19,19‐ethano‐ and 19,19‐dimethyl‐β‐retinals in the (all‐E), (9Z), and (11Z) isomeric forms are also reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)