A group 4 metallocene template synthesis of β,γ‐unsaturated ε‐hydroxy carboxylic acids

Abstract

AbstractThe reaction of (butadiene)zirconocene with hexacarbonyltungsten gives the metallacyclic [(π‐allyl)zirconoxy]carbene complex 7. This reagent adds to a variety of ketones to yield chiral nine‐membered metallacyclic ring systems (8). These systems are thus formed by means of 1,4‐selective coupling reactions of 1,3‐butadiene with W(CO)6 and an organic carbonyl compound at the zirconocene template. The ketones subjected to react with 7 include benzophenone, methyl vinyl ketone, cyclopentanone, and 3‐methoxyestra‐1,3,5(10)‐trien‐17‐one (12). The coupling products of 7 with cyclopentanone (8c) and 12 (8d‐A) were characterized by X‐ray crystal structure analyses. Of the four possible diastereomeric nine‐membered metallacyclic coupling products of 7 with 12 a single isomer [8d‐A with (13'S,17'R,2,3,4‐pS) configuration] was formed with ≥98% selectivity and isolated in 95% yield. Treatment of the complexes 8 in tetrahydrofuran with water and pyridine N‐oxide very effectively removed both transition metals with the formation of the corresponding β,γ‐unsaturated ε‐hydroxy carboxylic acids. The overall reaction sequence has thus converted the steroid ketone 12 very selectively to 5‐[3‐methoxy‐17β‐hydroxyestra‐1,3,5(10)‐trien‐17α‐yl]‐(E)‐pent‐3‐enoic acid (10d)