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

The chiral formylferrocenes 2-5 have been readily prepared in good yields b y ortho-lithiation of the TMS-blocked or unblocked aminoferrocenes and subs equent reaction with DMF. The stereochemistry of the reaction of 2 with org anometallic reagents has been examined. Reactions of 2 with Grignard and or ganolithium reagents gave the corresponding amino alcohol 6 in good yields with moderate to high diastereomeric excesses (up to 99%). When a dialkylzi ne was used as the nucleophile, a single diastereomer was obtained almost e xclusively. 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 a symmetric diethylzinc addition to benzaldehyde using formylferrocenes 2-5 o r ferrocenyl amino alcohols 6a, 13 as catalysts, especially with regard to the relationship between catalytic activity and the chirality of the diaste reomeric ferrocenes. Alkylation with 2, 3, and 6a gave (1R)-phenyl-1-propan ol in good yields with high ee values (87-91% eel. On the other hand, react ions with 4, 5, and 13 gave the (S)-product in low yield and with low ee (3 8-57% eel. The low stereoselectivities can be attributed to stereochemical mismatching in the zinc alkoxides derived from 4 and 5. With aromatic, stra ight-chain, or branched aliphatic aldehydes, the stereoselective alkylation successfully gave the corresponding alcohols in good to high optical purit ies when 2 or 3 was employed as the catalyst. The optically active 1,2-ferr ocenediol and -diphosphane have been prepared by means of the stereospecifi c substitution reaction with the amino alcohol 13 on treatment with acetic anhydride, followed by hydrolysis or substitution with diphenylphosphane.