AN EFFICIENT DIASTEREOSELECTIVE SYNTHESIS OF CHIRAL OXAZOLINYLFERROCENE COMPOUNDS

Chiral oxazolinylferrocenes 7 and 8 are synthesized from ethyl ferroce necarboxylate and amino acid-derived amino alcohols in overall 81-85% yields, through trimethylaluminum-mediated transamidation followed by ring formation with p-toluenesulfonyl chloride and triethylamine. Lith iation of the oxazolinylferrocenes under various reaction conditions a nd subsequent coupling reactions with electrophiles such as ClPPh(2), ClSnBu(3), ClSiMe(3), PhSSPh, DMF, and CO2 are described. Lithiated in termediates are found to have limited stability, depending on the solv ent and the temperature. In THF, the lithiated intermediate rapidly de composes at 25 degrees C: In Et(2)O, it is quite stable at 0 degrees C but mostly decomposes at 25 degrees C within 6 h. Lithiation of the o xazolinylferrocenes is directed by the oxazoline moiety and is highly diastereoselective in the case of 8. With s-BuLi in THF-cyclohexane, s everal ferrocene derivatives 11 are produced with diastereoselectiviti es of greater than or equal to 96:4. s-BuLi and n-BuLi give better sel ectivities and yields than t-BuLi. With s-BuLi, generally better diast ereoselectivities are obtained in THF-cyclohexane than in Et(2)O-cyclo hexanes. When ClPPh(2) is used as the electrophile, the s-BuLi in THF- cyclohexane system, however, gives variable yields depending on reacti on temperature and time. With n-BuLi in Et(2)O-hexanes at 25 degrees C , phosphino(oxazolinyl)ferrocene 11a is consistently obtained in moder ate yields with a 97:3 diastereoselectivity. Determination of the dias tereoselectivity and characterization of new chiral ferrocene compound s including one X-ray crystal structure are described.