In-depth structure–selectivity investigations on asymmetric, copper-catalyzed oxidative biaryl coupling in the presence of 5-cis-substituted prolinamines
In-depth structure–selectivity investigations on asymmetric, copper-catalyzed oxidative biaryl coupling in the presence of 5-cis-substituted prolinamines
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DOI：
10.1039/c4cy01676a
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发表时间：
2015-03
影响因子：
5
通讯作者：
Felix Prause;Benjamin Arensmeyer;B. Fröhlich;M. Breuning
中科院分区：
文献类型：
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作者：
Felix Prause;Benjamin Arensmeyer;B. Fröhlich;M. Breuning
13个新的和25个已知的脯氨酰胺携带一个额外的5-顺式取代基作为手性配体在不对称铜催化，氧化联芳基偶联3-羟基-2-萘甲酸酯进行了评价。全面的结构选择性研究表明，在5-顺式位置上的苯基和在吡咯烷氮上的小取代基（例如，Me）对于高水平的手性转移是必不可少的。不对称诱导的意义取决于环外氨基官能团的空间需求。在2-羟基-3-萘甲酸甲酯的偶联中，伯氨基允许高达36%ee，有利于P-对映异构体，而仲和叔氨基官能团（例如NMe 2，（S）-NHCH（Me）Ph）达到高达64%ee，有利于M-对映异构体。观察到脯氨酰胺和联萘酮的对映体过量之间的完全线性关系。所有的立体化学研究结果一致的机制提出，表明3-羟基-2-萘甲酸酯与笨重的酯基应允许更好的立体控制。事实上，当使用3-羟基-2-萘甲酸叔丁酯作为底物时，对映体过量提高到良好的87%。
Thirteen new and 25 known prolinamines carrying an additional 5-cis substituent were evaluated as the chiral ligands in asymmetric copper-catalyzed, oxidative biaryl coupling of 3-hydroxy-2-naphthoates. Comprehensive structure–selectivity investigations revealed that a phenyl group in the 5-cis position and a small substituent at the pyrrolidine nitrogen (e.g., Me) are essential for high levels of chirality transfer. The sense of the asymmetric induction depends on the steric demand of the exocyclic amino function. In the coupling of methyl 2-hydroxy-3-naphthoate, a primary amino group permitted up to 36% ee in favor of the P-enantiomer, while up to 64% ee in favor of the M-enantiomer was reached with secondary and tertiary amino functions (e.g. NMe2, (S)-NHCH(Me)Ph). A fully linear relationship between the enantiomeric excess of the prolinamine and the binaphthol was observed. A mechanism consistent with all stereochemical findings is proposed, indicating that 3-hydroxy-2-naphthoates with bulkier ester groups should permit better stereocontrol. Indeed, the enantiomeric excess was raised to good 87% when tert-butyl 3-hydroxy-2-naphthoate was used as the substrate.