Solution structure of unstabilized cyclic α-aminoorganolithiums by 13C, 15N, and 6Li NMR spectroscopy
Solution structure of unstabilized cyclic α-aminoorganolithiums by 13C, 15N, and 6Li NMR spectroscopy
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DOI：
10.1021/ja002308w
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发表时间：
2000-10-04
影响因子：
15
通讯作者：
Gawley, RE
中科院分区：
文献类型：
--
作者：
Low, E;Gawley, RE
有机锂试剂已成为现代有机合成中碳-碳键形成中不可缺少的试剂，手性、非消旋的有机锂试剂正发挥着越来越重要的作用。一个持续的兴趣点是具有立体金属碳的物种的结构和性质，因为这些物种中的许多都表现出非凡的构型稳定性。此外，构型稳定的、手性的、非外消旋的有机锂的亲电取代的立体过程从构型的完全保留到构型的完全反转，以及两者之间的不同点（文献3中有总结）。一个一致的趋势，解释这些反应的可变性尚未出现，所以结构研究的反应物种是感兴趣的。2-锂- n -甲基吡啶1和2-锂- n -甲基哌啶2和3与羰基和烷基卤化物反应产率很高。3-5这些不稳定的r -氨基有机锂在40℃以下构型稳定。6它们与大多数羰基亲电试剂反应产率高，在含金属碳（SE2ret）上构型保持100%，与烷基卤化物（SE2inv）发生不同程度的反转（SE2inv），取决于杂环的大小。例如，哌啶2与3-苯基-1-溴丙烷反应，在阴离子中心得到100%的反转；然而，吡咯烷1通过相互竞争的极性途径仅发生78-79%的反转反应。3,4由于亲电试剂容易还原，SET过程介入。具有赝赤道锂的刚性哌啶3在与烷基卤化物的反应中不能发生反转反应并经历SET过程，而羰基亲电试剂的保留取代则很容易发生。5有机锂1和有机锂2在发生se2转化反应的手性有机锂中是独特的，因为转化的过渡态不是介观稳定的。作为研究这些体系中异常构型稳定性和变化反应性的原因的一部分，我们使用6Li， 15N和13C NMR研究了这些物种在低温下的溶液结构，并在此报告结果。这三种有机锂都是由相应的锡烷通过Sn/Li交换制备的，如前所述。4-7为了避免过量丁基锂的并发症，并确保所观察到的物种只有r -氨基有机锂1-3，我们与每个锡烷反应了亚化学计量量的{6Li} BuLi8。对每一个的6Li光谱的检查显示只有一个尖锐的单线态，表明在100℃时只有一种有机锂物质存在。{6Li}有机锂配合物的聚集状态可以通过耦合碳信号的多重性或利用经验关系J) 17 Hz/n从1J （13C-6Li）耦合常数的大小来确定，其中n是聚集数。10
Organolithium reagents have become indispensable in the formation of carbon-carbon bonds in modern organic synthesis and chiral, nonracemic organolithium reagents are playing an increasingly important role. 1 A continuing point of interest is the structure and properties of species having a stereogenic metal-bearing carbon, since many of these species exhibit extraordinary configurational stability. Furthermore, the steric course of electrophilic substitutions2 of configurationally stable, chiral, nonracemic organolithiums varies from complete retention to complete inversion of configuration, and various points between (summarized in ref 3). A consistent trend that explains the variabilities of these reactions has not yet emerged, so structural studies of the reactive species are of interest. 2-Lithio-N-methylpyrrolidines, 1, and 2-lithio-N-methylpiperidines, 2 and 3, react with carbonyls and alkyl halides in excellent yields. 3-5 These unstabilized R-aminoorganolithiums are configurationally stable up to-40 C. 6 They react in high yield with most carbonyl electrophiles with 100% retention of configuration at the metal-bearing carbon (SE2ret) and with varying degrees of inversion (SE2inv) with alkyl halides, depending on the size of the heterocyclic ring. 3, 4 For example, piperidine2 reacts with 3-phenyl-1-bromopropane to give 100% inversion at the anionic center; however, pyrrolidine 1 reacts with only 78-79% inversion through competing polar pathways. 3, 4 With electrophiles that are easily reduced, SET processes intervene. 3 Rigid piperidine 3, having a pseudoequatorial lithium, cannot react with inversion and undergoes SET processes in reactions with alkyl halides, whereas retentive substitution by carbonyl electrophiles is facile. 5 Organolithiums 1 and 2 are unique among chiral organolithiums that undergo SE2inv reactions in that the transition state for inversion is not mesomerically stabilized. As part of an investigation into the reasons for the extraordinary configurational stability and varying reactivity in these systems, we have used 6Li, 15N, and 13C NMR to investigate the solution structure of these species at low temperature, and report the results herein.All three organolithium species were prepared by Sn/Li exchange from the corresponding stannanes, as reported previously. 4-7 To avoid complications from excess butyllithium, and to ensure that the species being observed were only R-aminoorganolithiums 1-3, we reacted a substoichiometric amount of {6Li} BuLi8 with each stannane. Examination of the 6Li spectra of each revealed only one sharp singlet, indicating the presence of only one organolithium species at-100 C. 9 The aggregation state of a {6Li} organolithium complex can be determined from the multiplicity of a coupled carbon signal or from the magnitude of the 1J (13C-6Li) coupling constant using the empirical relationship J) 17 Hz/n, where n is the aggregation number. 10