STEREOSELECTIVE FORMATION AND ELECTROPHILIC SUBSTITUTION OF ALDEHYDE HYDRAZONE LITHIO ANIONS

The stereochemistry of the lithio anions (4) formed by deprotonation of aldehyde dimethylhydrazones (RCH2CHNN(CH3)2; R = H, C6H5, Si(CH3)3) has been determined by 1H 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 C1-C2 (R = C6H5, Si(CH3)3) bond and predominant Z stereochemistry about the C-N bond. For propionaldehyde dimethylhydrazone (R = CH3), LDA/THF deprotonation gave >95% EC-C,ZC-N lithio anion without any detectable ZC-C,EC-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 EC-C,ZC-N lithio anion (>98%) while deprotonation with LDA/THF/HMPA gave the ZC-C,EC-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 EC-C,ZC-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.