Influence of Steric Factors on Chiral Lithium Amide Aggregates

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 2:2 ladder-type mixed aggregate with n-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 (S)-N-isobutyl-3-methyl-1-((triisopropylsilyl)­oxy)­butan-2-amide
forms both a 2:2 mixed aggregate and a 2:1 mixed trimer with n-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 (R)-N-(1-phenyl-2-((triisopropylsilyl)­oxy)­ethyl)­propan-2-amide.