A Novel Method for a Stereoselective Synthesis of Trisubstituted Olefin Using Tricarbonyliron Complex:  A Highly Stereoselective Synthesis of (all-E)- and (9Z)-Retinoic Acids

• Published in: Journal of organic chemistry Vol. 62; no. 13; pp. 4343 - 4348
• Main Authors: Wada, Akimori, Hiraishi, Saeko, Takamura, Norio, Date, Tadamasa, Aoe, Keiichi, Ito, Masayoshi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.06.1997
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo961041+

In order to establish the stereoselective synthesis of retinoic acids, which are ligand molecules of the retinoic acid receptors (RARs, all-E-isomer) and the retinoid X receptors (RXRs, 9Z-isomer), the reaction of β-ionone−tricarbonyliron complex 7 with carbanions was investigated. Treatment of 7 with the lithium salt of acetonitrile afforded (7E,9E)-β-ionylideneacetonitrile−tricarbonyliron complex 8 exclusively, via addition, dehydration, and migration of tricarbonyliron complex. On the contrary, the reaction of 7 with the lithium enolate of ethyl acetate and subsequent dehydration by thionyl chloride afforded the ethyl (7E,9Z)-β-ionylideneacetate−tricarbonyliron complex 16b predominantly. These compounds (8 and 16b) were converted to the corresponding β-ionylideneacetaldehyde−tricarbonyliron complexes (10 and 22) in excellent yields, respectively. The Emmons−Horner reaction of these compounds with C5-phosphonate followed by the sequence of decomplexation and alkaline hydrolysis gave the corresponding retinoic acids (26 and 29).