Asymmetric Mannich-Type Addition of Ketene Silyl Acetals and Thioacetals to N,N-Dialkylhydrazones

Abstract

The choice of the 2,6-diphenylpiperidine moiety as the N,N-dialkylamino auxiliary in simple aliphatic dialkylhydrazones and the use of scandium triflate as the catalyst in aqueous media appear as the key strategies that enable the highly diastereoselective nucleophilic addition of ketene silyl acetals and thioacetals. The reaction proceeds to afford the expected adducts in high yields (88-98%) and diastereomeric ratios of up to 99:1. N-N bond cleavage of adducts affords enantiomerically pure β-amino esters.

Key words

asymmetric synthesis - hydrazones - ketene silyl acetals - ketene silyl thioacetals - diastereoselectivity

References

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14

Yield of compound 10 increases to 81% when 4 equivalents of 8 and 0.4 M THF-H₂O (9:1) were used.

15

Recently we have found out that N,N-dialkylhydrazones from enolizable aldehydes react with nitroalkenes, through the tautomeric ‘ene-hydrazine’ form, in the presence of thioureas as H-bonding catalysts: Pettersen, D.; Herrera, R. P.; Bernardi, L.; Fini, F.; Sgarzani, V.; Fernández, R.; Lassaletta, J. M.; Ricci, A., Synlett 2006, in press.

17

These compounds proved to be rather unstable and did not resist purification by column chromatography but the crude products were obtained with a high degree of purity.

23

CCDC 289555 contains the supplementary crystallographic data for 16. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: [phone]; or [e-mail]].