N-甲基-N-芳基乙酰胺的立体异构体及其衍生的烯醇盐：对不对称 Hartwig 吲哚环化反应的影响。
Rotational isomers of N-methyl-N-arylacetamides and their derived enolates: implications for asymmetric Hartwig oxindole cyclizations.
机构信息
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
出版信息
J Org Chem. 2013 Apr 19;78(8):4083-9. doi: 10.1021/jo400385t. Epub 2013 Apr 9.
Abstract
The rotational preferences of N-(2-bromo-4,6-dimethylphenyl)-N-methyl 2-phenylpropanamide were studied as a model of precursors for Hartwig asymmetric oxindole cyclizations. The atropisomers of this compound were separated by flash chromatography, and then the enantiomers were resolved and the interconversions of the stereocenter and the N-Ar axis were studied. Under thermal conditions, the axis is very stable. Under the basic conditions of the Hartwig cyclization, both the stereocenter and the chiral axis equilibrate via enolate formation. The N-Ar rotation barrier of a 2-phenylacetamide analogue was reduced from 31 kcal mol(-1) in the precursor to 17 kcal mol(-1) in the enolate. Reasons for this dramatic barrier reduction and implications of both N-Ar and amide C-N rotations for Hartwig cyclizations are discussed.
摘要
我们研究了 N-(2-溴-4,6-二甲基苯基)-N-甲基 2-苯基丙酰胺的旋转偏好，将其作为 Hartwig 不对称氧化吲哚环化反应前体的模型。通过快速色谱法分离该化合物的对映异构体，然后拆分对映异构体，并研究了立体中心和 N-Ar 轴的相互转化。在热条件下，该轴非常稳定。在 Hartwig 环化的碱性条件下，通过烯醇化物的形成，立体中心和手性轴都达到平衡。2-苯乙酰胺类似物的 N-Ar 旋转势垒从前体中的 31 kcal mol(-1)降低到烯醇化物中的 17 kcal mol(-1)。讨论了这种显著的势垒降低的原因，以及 N-Ar 和酰胺 C-N 旋转对 Hartwig 环化的影响。
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