COMPLEX INDUCED PROXIMITY EFFECTS - BETA-LITHIATIONS OF CARBOXAMIDES

The R*,S* and the R*,R* diastereomers of N,N-diisopropyl-2,3-dideuterio-2-methyl-3-phenylpropanamide (5,6) have been used to investigate the diastereoselectivity of the beta-lithiation of N,N-diisopropyl-2-methyl-3-phenylpropanamide (4). The beta-lithiation of 4 is highly diastereoselective with the beta-proton that is in the same relative position as the beta-proton of diastereomer 6 being preferentially removed. The beta-lithio species derived from 4 is shown to be a pyramidal, organolithium reagent based on C-13 NMR. Lithiation of the R*,S* and the R*,R* diastereomers of N,N-diisopropyl-2-methyl-3-(phenylthio)butanamide (7, 8) and N,N-diisopropyl-2,3-dimethyl-4-pentenamide (9, 10) occur at the beta-position. Lithiation of the R*,S* and R*,R* diastereomers of N,N-diisopropyl-2-methyl-3-phenylbutanamide (11, 12) occurs at the beta-position for 11 and at the alpha-position for 12. A conformational model is shown to correlate with these observations. The beta-lithio species formed do not react diastereospecifically.