Influence of Steric Factors on Chiral Lithium Amide Aggregates

Abstract

The solution structures of three mixed aggregates dissolved in toluene-<i>d</i>₈ consisting of the lithiated amides derived from (<i>S</i>)-<i>N</i>-isopropyl-1-((triisopropylsilyl)­oxy)­propan-2-amine, (<i>R</i>)-<i>N</i>-(1-phenyl-2-((triisopropylsilyl)­oxy)­ethyl)­propan-2-amine, or (<i>S</i>)-<i>N</i>-isobutyl-3-methyl-1-((triisopropylsilyl)­oxy)­butan-2-amine and <i>n</i>-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 (<i>S</i>)-<i>N</i>-isopropyl-1-((triisopropylsilyl)­oxy)­propan-2-amide forms mostly a 2:2 ladder-type mixed aggregate with <i>n</i>-butyllithium. Increase of steric hindrance of the R₁ and R₂ groups suppresses the formation of the 2:2 mixed aggregate and promotes formation of a 2:1 mixed aggregate. We observe that lithium (<i>S</i>)-<i>N</i>-isobutyl-3-methyl-1-((triisopropylsilyl)­oxy)­butan-2-amide forms both a 2:2 mixed aggregate and a 2:1 mixed trimer with <i>n</i>-butyllithium. Further increase in the steric hindrance of R₁ and R₂ groups results in the formation of only 2:1 mixed aggregate as observed with lithium (<i>R</i>)-<i>N</i>-(1-phenyl-2-((triisopropylsilyl)­oxy)­ethyl)­propan-2-amide