NMR SPECTROSCOPIC DETERMINATION OF THE ABSOLUTE CONFIGURATION OF CHIRAL SULFOXIDES VIA N-(METHOXYPHENYLACETYL)SULFOXIMINES
NMR SPECTROSCOPIC DETERMINATION OF THE ABSOLUTE CONFIGURATION OF CHIRAL SULFOXIDES VIA N-(METHOXYPHENYLACETYL)SULFOXIMINES
复制标题
通过 N-(甲氧基苯基乙酰基)亚磺胺对手性亚砜的绝对构型进行核磁共振波谱测定
DOI：
10.1021/ja992730g
复制
发表时间：
1999
影响因子：
15
通讯作者：
T. Kusumi
中科院分区：
文献类型：
--
作者：
Tetsuya Yabuuchi;T. Kusumi
越来越多的关于 NMR 方法的报告正在发表，这些报告能够阐明手性仲醇、1 胺、2 和羧酸的绝对构型。 3 然而，对于手性亚砜，除了 X 射线晶体学之外，很少有方法可以确定其绝对构型，尽管亚磺酰基部分是生物活性天然产物和合成药物中常见的重要官能团。 9-蒽基-1, 1, 1-三氟乙醇、4 R-甲氧基苯乙酸、5和(R)-(-)-N-(3, 5-二硝基苯甲酰基)-R-苯乙胺6已被开发作为推导亚砜绝对构型的NMR试剂。这些试剂通过其酸性OH基团和亚砜的氧原子之间的氢键形成络合物，并且由于络合物的不稳定性，非对映异构体络合物之间的化学位移差异通常非常小或者在某些情况下是非系统性的，这使得这些方法有些不确定。难以假设脆弱复合物的稳定构象也可能是这些方法的固有缺点。我们认为，如果某种手性各向异性试剂7能够与立体硫或亚砜氧共价键合，则手性助剂芳香环的各向异性效应将比传统的氢键配合物更显着。在亚砜氧上引入手性各向异性部分似乎不太有希望，因为酰化时会发生普默勒重排，并且手性信息将因此丢失。因此，我们专注于用 O-异三甲苯基磺酰基羟胺 9 进行亚砜的胺化，并完全保留硫原子的手性。 10 我们的方法策略如方案 1 所示。当在立体硫原子处引入氨基时，(R)-和 (S)-甲氧基苯乙酸可以在氮原子处特异性引入。所得N-(甲氧基苯乙酰基)亚磺酰亚胺的稳定构象很容易推断为[I], 11，因为替代构象[II]和[III]将因电负性原子之间严重的偶极-偶极排斥而不稳定。绝对配置将是
An increasing number of reports is being published on the NMR methods that enable the elucidation of the absolute configuration of chiral secondary alcohols, 1 amines, 2 and carboxylic acids. 3 In respect to chiral sulfoxides, however, there have been very few methods to determine their absolute configuration except for X-ray crystallography, although the sulfinyl moiety is an important functional group that is frequently found in biologically active natural products and synthetic drugs. 9-Anthryl-1, 1, 1-trifluoroethanol, 4 R-methoxyphenylacetic acid, 5 and (R)-(-)-N-(3, 5-dinitrobenzoyl)-R-phenylethylamine6 have been developed as the NMR reagents for deducing the absolute configuration of sulfoxides. These reagents form complexes by hydrogen bonds between their acidic OH groups and the oxygen atom of the sulfoxide, and because of the instability of the complexes, the chemical shift differences between the diastereomeric complexes are usually very small or in some cases nonsystematic, which makes these methods somewhat uncertain. Difficulty in assuming the stable conformation of the fragile complexes may also be an intrinsic drawback of these methods. We considered that, if a certain chiral anisotropic reagent7 could be covalently bonded to the stereogenic sulfur or the sulfoxide oxygen, the anisotropic effect from the aromatic ring of the chiral auxiliary would be more significant than the conventional hydrogen-bonded complexes. Introduction of a chiral anisotropic moiety at the sulfoxide oxygen seems less promising because the Pummerer rearrangement8 would occur on acylation, and the information on the chirality would thus be lost. Therefore, we focused on amination of sulfoxide with O-mesitylsulfonylhydroxylamine9 which proceeded with complete retention of chirality at the sulfur atom. 10 The strategy of our method is outlined in Scheme 1.When an amino group is introduced at the stereogenic sulfur atom,(R)-and (S)-methoxyphenylacetic acids can be introduced specifically at the nitrogen atom. The stable conformation of the resulting N-(methoxyphenylacetyl) sulfoximine is easily deduced to be [I], 11 because the alternative conformations [II] and [III] will be destablized by the serious dipole-dipole repulsion between the electronegative atoms. The absolute configurations will be