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.

本研究针对三种溶解于氘代甲苯(toluene-d8)中的混合聚集体的溶液结构展开表征，该类聚集体由分别源自(S)-N-异丙基-1-((三异丙基硅基)氧基)丙-2-胺、(R)-N-(1-苯基-2-((三异丙基硅基)氧基)乙基)丙-2-胺以及(S)-N-异丁基-3-甲基-1-((三异丙基硅基)氧基)丁-2-胺的锂化酰胺，与正丁基锂(n-butyllithium)共同构成。表征过程采用了多种核磁共振实验技术，包括结合扩散系数-式量关联分析（D-FW）的扩散有序NMR光谱法，以及其他一维、二维核磁共振技术。
本研究发现，手性锂酰胺的R1、R2基团空间位阻可调控该类混合聚集体的聚集状态。当R2基团位阻较小时，锂化(S)-N-异丙基-1-((三异丙基硅基)氧基)丙-2-胺与正丁基锂主要形成2:2型梯状混合聚集体。增大R1与R2基团的空间位阻会抑制2:2型混合聚集体的生成，并促进2:1型混合聚集体的形成。实验观察到，锂化(S)-N-异丁基-3-甲基-1-((三异丙基硅基)氧基)丁-2-胺可与正丁基锂同时形成2:2型混合聚集体与2:1型混合三聚体。进一步增大R1、R2基团的空间位阻则仅会生成2:1型混合聚集体，这与锂化(R)-N-(1-苯基-2-((三异丙基硅基)氧基)乙基)丙-2-胺的实验结果一致。