Synthesis of Farnesol Isomers via a Modified Wittig Procedure

Abstract

[structure: see text] The four olefin stereoisomers of farnesol have been synthesized from readily available nerylacetone or commercial geranylacetone. A new variation on the use of beta-oxido ylides favored the (2Z)-stereoisomers, whereas the (2E)-isomers were obtained through a classical Horner-Wadsworth-Emmons condensation with triethyl phosphonoacetate and reduction of the resulting ester.

Recent Applications of the Horner-Wadsworth-Emmons Reaction to the Synthesis of Natural Products

“…An example of this is the synthesis of (2E,6Z)-farnesol and (E,E,E)-geranylgeraniol reported by Yu [56], in which polyprenylated methyl ketones undergo HWE olefination with triethylphosphonoacetate in the presence of NaH/15-c-5 with high E-diasteroselectivity.…”

Preparation of trialkyl-substituted olefins by ruthenium catalyzed cross-metathesis

“…The E/Z stereochemistry of such olefins is an important feature in particular in the area of naturally occurring isoprenoid compounds, as they are predominantly not mixtures, but single-isomer products. Prominent examples, of which their unambiguous stereochemistry is defined by the biosynthetic pathway, are various plant cis-trans(Z,E)-polyprenols (1) and dolichols (2) [1], (all-E)-polyprenols (3), tocotrienols (4) [2], (all-E-)-coenzyme Q 10 (5) [3], (E)-phytol (6) [4], and vitamin K 1 (7) [5] (Fig. 1).…”

“…Modified Wittig procedures favour the Z-isomer, and classical Horner-Wadsworth-Emmons condensation protocols deliver mostly E-stereochemistry [6,7]. Exceptionally high stereoselectivities can be obtained with the Negishitype zirconium catalyzed carboalumination of acetylenes [8][9][10] which has been applied e.g.…”

Stereocontrolled regeneration of olefins from epoxides

“…Therefore alcohol 8 was prepared from farnesyl acetone ( 6 ). 11 A Horner-Wadsworth-Emmons (HWE) condensation of triethyl phosphonoacetate and farnesyl acetone ( 6 ) provided ester 7 as a mixture of olefin isomers (approximately 10:1 E : Z ). Because the E - and Z -isomers were not readily separable by column chromatography at this stage, they were carried forward as a mixture.…”

“…After the esters were reduced to alcohols by treatment with LiAlH 4 , the individual isomers were obtained by column chromatography to afford pure (2 E , 6 E , 10 E )–geranylgeraniol ( 8 ) in 61% yield. 11 Regioselective formation of epoxygeranylgeraniol ( 9 ) was accomplished by treatment of alcohol 8 with vanadyl acetylacetonate and TBHP. 12,13 The resulting epoxide then was allowed to react with MsCl, followed by LiBr to afford the primary bromide 10 .…”