Influence of steric factors on chiral lithium amide aggregates.

ABSTRACT

The solution structures of three mixed aggregates dissolved in toluene-d8 consisting of the lithiated amides derived from (S)-N-isopropyl-1-((triisopropylsilyl)oxy)propan-2-amine, (R)-N-(1-phenyl-2-((triisopropylsilyl)oxy)ethyl)propan-2-amine, or (S)-N-isobutyl-3-methyl-1-((triisopropylsilyl)oxy)butan-2-amine and n-butyllithium are characterized by various NMR experiments including diffusion-ordered NMR spectroscopy with diffusion coefficient-formula weight correlation analyses (D-FW) and other one- and two-dimensional NMR techniques. We report that steric hindrance of R1 and R2 groups of the chiral lithium amide controls the aggregation state of the mixed aggregates. With a less hindered R2 group, lithium (S)-N-isopropyl-1-((triisopropylsilyl)oxy)propan-2-amide forms mostly a 22 ladder-type mixed aggregate with n-butyllithium. Increase of steric hindrance of the R1 and R2 groups suppresses the formation of the 22 mixed aggregate and promotes formation of a 21 mixed aggregate. We observe that lithium (S)-N-isobutyl-3-methyl-1-((triisopropylsilyl)oxy)butan-2-amide forms both a 22 mixed aggregate and a 21 mixed trimer with n-butyllithium. Further increase in the steric hindrance of R1 and R2 groups results in the formation of only 21 mixed aggregate as observed with lithium (R)-N-(1-phenyl-2-((triisopropylsilyl)oxy)ethyl)propan-2-amide.