Diastereoselective 1,2-Addition of Organometallic Reagents to Chiral Formylferrocenes Leading to Enantiomerically Pure Ferrocenyl Amino Alcohols: Application to Asymmetric Dialkylzinc Addition to Aldehydes and Synthesis of Optically Active 1,2-Homodisubstituted Ferrocenes

Abstract

The chiral formylferrocenes 2−5 have been readily prepared in good yields by ortho-lithiation of the TMS-blocked or -unblocked aminoferrocenes and subsequent reaction with DMF. The stereochemistry of the reaction of 2 with organometallic reagents has been examined. Reactions of 2 with Grignard and organolithium reagents gave the corresponding amino alcohol 6 in good yields with moderate to high diastereomeric excesses (up to 99%). When a dialkylzinc was used as the nucleophile, a single diastereomer was obtained almost exclusively. This reaction may be rationalized in terms of an autocatalytic mechanism; the zinc alkoxide 7 generated in situ functions as an activator of dialkylzinc, which then adds to the formyl group. We have examined the asymmetric diethylzinc addition to benzaldehyde using formylferrocenes 2−5 or ferrocenyl amino alcohols 6a, 13 as catalysts, especially with regard to the relationship between catalytic activity and the chirality of the diastereomeric ferrocenes. Alkylation with 2, 3, and 6a gave (1R)-phenyl-1-propanol in good yields with high ee values (87−91% ee). On the other hand, reactions with 4, 5, and 13 gave the (S)-product in low yield and with low ee (38−57% ee). The low stereoselectivities can be attributed to stereochemical mismatching in the zinc alkoxides derived from 4 and 5. With aromatic, straight-chain, or branched aliphatic aldehydes, the stereoselective alkylation successfully gave the corresponding alcohols in good to high optical purities when 2 or 3 was employed as the catalyst. The optically active 1,2-ferrocenediol and -diphosphane have been prepared by means of the stereospecific substitution reaction with the amino alcohol 13 on treatment with acetic anhydride, followed by hydrolysis or substitution with diphenylphosphane.