jo971700y_si_002.pdf (397.05 kB)
1,4-Di-O-tert-alkyl-l-threitols as Chiral Auxiliaries in the Asymmetric Nucleophilic Addition of Alkyllithiums to Hydrazones†
journal contributionposted on 1998-02-14, 00:00 authored by Yu-Tsai Hsieh, Gene-Hsiang Lee, Yu Wang, Tien-Yau Luh
The applications of 1,4-di-O-tert-alkyl-l-threitols as chiral auxiliaries in the asymmetric nucleophilic addition of alkyllithiums to hydrazones are investigated. Chiral acetal-hydrazones 9, obtained from the chiral acetals 8 by ozonolysis followed by treatment with dimethylhydrazine, are allowed to react with organolithium reagents in toluene at − 78 °C to give 15 with excellent diastereoselectivity. The stereochemical assignments were based on the X-ray crystal structure of 17a. The absolute configuration at C2 of the major isomer of the adducts 15 was thereby determined to be S. The nucleophile thus attacked from the si face of the CN moiety. The effect of solvent on the diastereoselectivity of the reactions of 9 with organolithium reagents is reported. Polar aprotic solvent shows poor diastereoselectivity, and the diastereoselectivity is reversed when the reaction is carried out in THF. Reaction of dl-14 with methyllithium has been studied for comparison purposes and the reaction shows the opposite selectivity. Chelation intermediates 18 and 26 are proposed for these reactions to account for the observed stereoselectivities.