Stereoselective synthesis of retinoid isomers using tricarbonyliron complex and its application

Abstract

In order to establish the stereoselective synthesis of retinoid isomers, the reaction of β-ionone-tricarbonyliron complex 2 with carbanions was investigated. Treatment of 2, prepared from the reaction of β-ionone and dodecacarbonyltriiron, with the lithium salt of acetonitrile afforded 3. In contrast, the reaction of 2 with the lithium enolate of ethyl acetate, and subsequent dehydration by thionyl chloride, provided the ethyl 9Z-β-ionylideneacetate 7 predominantly. These compounds (3 and 7) were converted to the corresponding β-ionylideneacetaldehydes (4 and 8) in excellent yields. The Emmons-Horner reaction of these aldehydes with C5-phosphonate, followed by the sequence of decomplexation and alkaline hydrolysis, gave the corresponding all-E- and 9Z-retinoic acids (12 and 15). The Peterson reaction of 4 with ethyl trimethylsilylacetate provided the 11Z-isomer 17 preferentially, accompanied by the 11E-isomer. The ester 17 was transformed into 11Z-retinal 26. Applying this synthetic methodology, various 9-demethyl-9-substituted 11Z-retinals 36 were prepared. © 1999 IUPAC.