An Efficient Diastereoselective Synthesis of Chiral Oxazolinylferrocene Compounds

Chiral oxazolinylferrocenes 7 and 8 are synthesized from ethyl ferrocenecarboxylate 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. Lithiation of the oxazolinylferrocenes under various reaction conditions and subsequent coupling reactions with electrophiles such as ClPPh 2, ClSnBu 3, ClSiMe 3, PhSSPh, DMF, and CO 2 are described. Lithiated intermediates are found to have limited stability, depending on the solvent and the temperature. In THF, the lithiated intermediate rapidly decomposes at 25 °C: In Et 2 O, it is quite stable at 0 °C but mostly decomposes at 25 °C within 6 h. Lithiation of the oxazolinylferrocenes is directed by the oxazoline moiety and is highly diastereoselective in the case of 8 . With s- BuLi in THF−cyclohexane, several ferrocene derivatives 11 are produced with diastereoselectivities of ≥96:4. s- BuLi and n- BuLi give better selectivities and yields than t- BuLi. With s- BuLi, generally better diastereoselectivities are obtained in THF−cyclohexane than in Et 2 O−cyclohexanes. When ClPPh 2 is used as the electrophile, the s- BuLi in THF−cyclohexane system, however, gives variable yields depending on reaction temperature and time. With n- BuLi in Et 2 O−hexanes at 25 °C, phosphino(oxazolinyl)ferrocene 11a is consistently obtained in moderate yields with a 97:3 diastereoselectivity. Determination of the diastereoselectivity and characterization of new chiral ferrocene compounds including one X-ray crystal structure are described.