1,4-Di-O-tert-alkyl-l-threitols as Chiral Auxiliaries in the Asymmetric Nucleophilic Addition of Alkyllithiums to Hydrazones

Abstract

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 C 2 of the major isomer of the adducts 15 was thereby determined to be S. The nucleophile thus attacked from the si face of the CdN 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.S0022-3263(97)01700-3 CCC: $15.00

Electrophilic and Nucleophilic Reactivities of the Azomethine Carbon of SAMP-Hydrazones: Stereoselective Synthesis of γ-Amino Ketone Derivatives

“…On the other hand, the azomethine carbon of hydrazones can also behave as an electrophilic center of low reactivity (thereby acting as electron-rich imines), able to suffer addition of strong nucleophiles such as organometallic reagents. , Furthermore, the use of chiral hydrazones to achieve stereocontrol during the above reaction is a well-established method for the asymmetric synthesis of optically enriched amines, and in particular, SAMP derivatives have proved to be particularly well suited for this purpose . In this context, we decided to take advantage of this reaction for the optimal employment of the chiral information in the original reagent: After the excellent induction effected in the addition of SAMP-hydrazone 1 as a d 1 synthon (Umpolung), the chiral auxiliary can be used again for the stereocontrolled generation of a second chiral center.…”