Stereoselective formation and electrophilic substitution of aldehyde hydrazone lithio anions Academic Article uri icon


  • The stereochemistry of the lithio anions (4) formed by deprotonation of aldehyde dimethylhydrazones (RCH 2 CHNN(CH 3 ) 2 ; R = H, C 6 H 5 , Si(CH 3 ) 3 ) has been determined by 1 H NMR spectroscopy and trapping experiments. Deprotonation by lithium diisopropylamide (LDA) in tetrahydrofuran (THF) or LDA in THF with hexamethylphosphoric triamide (HMPA) gave anionic species 4 with E stereochemistry about the C 1 -C 2 (R = C 6 H 5 , Si(CH 3 ) 3 ) bond and predominant Z stereochemistry about the C-N bond. For propionaldehyde dimethylhydrazone (R = CH 3 ), LDA/THF deprotonation gave >95% E C-C ,Z C-N lithio anion without any detectable Z C-C ,E C-N lithio anion, but deprotonation with LDA/THF/HMPA gave a 15/85 mixture of the two lithio anions, respectively. Deprotonation of the chiral propionaldehyde hydrazone made from (S)-1-amino-2-methoxymethylpyrrolidine (SAMP) and propionaldehyde with LDA/THF gave the E C-C ,Z C-N lithio anion (>98%) while deprotonation with LDA/THF/HMPA gave the Z C-C ,E C-N lithio anion (>95%). Benzylation and hydrolysis of these two anionic species gave (S)-2-methyl-3-phenylpropanal (82% ee) and (R)-2-methyl-3-phenylpropanal (10% ee), respectively. Deprotonation of the chiral SAMP hydrazone of phenylacetaldehyde gave predominantly the E C-C ,Z C-N lithio anion which was methylated with 66% stereoselectivity. Thus, in two-step asymmetric electrophilic syntheses employing chiral aldehyde hydrazones the deprotonation step is seen to be more stereoselective than the alkylation step. Models for the transition states involved in LDA deprotonations of monosubstituted carbonyl compounds and derivatives in the presence and absence of HMPA are presented. © 1979, American Chemical Society. All rights reserved.

author list (cited authors)

  • Davenport, K. G., Eichenauer, H., Enders, D., Newcomb, M., & Bergbreiter, D. E

complete list of authors

  • Davenport, Kenneth G||Eichenauer, Herbert||Enders, Dieter||Newcomb, Martin||Bergbreiter, David E

publication date

  • January 1, 1979 11:11 AM