Hydrozirconation for unsaturated fatty acid derivatives

In the hydrozirconation reaction, developed by Schwartz and coworkers, bis (π‐cyclopentadienyl) zirconium hydridochloride Cp 2 ‐Zr(H)Cl, is added to the double bond of an olefin. The organozirconium intermediate can be functionalized by reaction with a variety of electrophiles such as oxygen, halogens, acetyl chloride and carbon monoxide. Furthermore, the double bond can be reformed by treatment with a hydride acceptor such as triphenylmethyl tetrafluoroborate. When a short‐chain internal olefin is hydrozirconated, the initially formed alkylzirconium intermediate is rapidly isomerized to a compound in which the zirconium moiety is bound to the sterically least hindered position, which most often is the terminal position. The isomerization occurs rapidly at room temperature in contrast to the corresponding organoboron or aluminum compounds, which slowly positionally rearrange only at elevated temperatures. Because of the facile isomerization of internal alkylzirconium compounds to the terminal ones, we investigated application of the reaction to unsaturated fatty acids such as oleic and erucic acids. However, reactions on long‐chain alkenes (such as oleic acid) are frequently much slower than those conducted on shorter‐chain alkenes, and attention must be given to optimizing the reaction conditions if good yields are to be obtained. It would also be necessary to find an easily removable protecting group for the carboxylic function, as Cp 2 Zr(H)Cl reduces carboxylic acids to alcohols. We found that the 4,4‐dimethyl‐2oxazoline function is a suitable protecting. group, and therefore synthesized the oxazolines from oleic acid and erucic acid. Hydrozirconation of the 4,4‐dimethyl‐2‐oxazoline of oleic acid followed by oxidation with t ‐butyl hydroperoxide and conversion to methyl esters, gave methyl 3‐hydroxy and methyl 18‐hydroxy stearate in 13% and 17% yield, respectively. The relatively low yield is due to competing hydrogenation, the mechanism of which is discussed. Recent results indicate that the carboxyl group can be protected as t ‐butyl esters in the hydrozirconation and that oleyl alcohol derivatives can also be used. To understand the isomerization pattern in hydrozirconation, the reaction with α,β‐ and β,γ‐unsaturated fatty acid oxazolines is discussed. Possibilities of making the hydrozirconation reaction catalytic by binding of the hydrozirconation reagent to a solid support as well as the synthetic potential in combining hydrozirconation with the olefin metathesis reaction are briefly reviewed.