The Unique Behavior of a Chiral Binaphthyl Oxazoline in the Presence of Cu(I) and Its Role as a Chiral Catalyst.
The Unique Behavior of a Chiral Binaphthyl Oxazoline in the Presence of Cu(I) and Its Role as a Chiral Catalyst.
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Cu(I) 存在下手性联萘恶唑啉的独特行为及其作为手性催化剂的作用。
DOI：
10.1002/chin.199825050
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
A. Price
中科院分区：
文献类型：
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作者：
A. Meyers;A. Price
我们多年来一直致力于通过 1-溴-2-恶唑啉基萘 11 和 8-溴-1-恶唑啉基萘 3 的乌尔曼偶联获得手性联萘。在这两种情况下，分别以高非对映选择性 (> 99%) 获得了联萘偶联产物 2 和 4。 1, 2 鉴于许多实验室在利用手性联萘（主要是 2 所描述的类型）作为手性催化剂方面付出了巨大的努力，我们最近将注意力集中在较少研究的 4 1, 1', 8, 8'-系统, 4。在我们最近的初步报告中，2 我们表明，手性溴代衍生物 3 在含有活化铜粉的回流加热时产生单一非对映异构体(aS,S)-4即使在长时间加热后也对阻转异构现象相当稳定。令人惊讶的是，将4在145℃下加热24小时得到4和5以75:25比例的混合物，仅在室温下静置后返回到4。 4的X射线结构2显示该构型（方案1、4A）优选在68位同时具有萘环并且恶唑啉几乎与萘邻位。恶唑啉环似乎没有显示出关于连接的 CC 键的任何旋转（方案 1A，键 a），因为这会将叔丁基置于萘环的 π 面中。由于 4:5 的 3:1 混合物在室温下返回到 > 98% 4，这支持了早期的报告5，即许多 1, 1', 8, 8'-联萘的阻转异构化的活化势垒相当低。当 sp2 取代基存在于 8、8' 位时尤其如此。 sp3 取代基 OH 和 OMe 的势垒要高得多，因为它们在旋转过程中呈现出更大的体积，并且这些衍生物确实已拆分为对映体。 6-8 Fuji4 还报道了在含有磷取代基的类似系统中容易发生阻转异构化，并将这种行为归因于萘环平面性的扭曲，这一点已被 X 射线数据证实。仔细检查42的X射线结构表明萘环没有这种扭曲，因此4作为唯一的阻转异构体在室温下的稳定性一定是由于其他因素（见上文）。尽管4至5的低旋转势垒可能妨碍其作为手性催化剂的使用，但我们仍然认为有必要进一步研究。我们惊讶地发现，当乌尔曼偶联在 DMF 中代替吡啶进行时，获得的唯一产物是 aR-阻转异构体 5，并且 NMR 检测不到任何 aS-衍生物。 2 当后处理中除去铜盐时，aR-阻转异构体作为结晶固体在室温下稳定数小时，并且在零下 20°C 下无限期稳定。然而，当在室温下溶解在各种溶剂中时，它会迅速完全转化回 aS-异构体 4。最令人感兴趣的是，只有在将含有 1.0 当量 CuBr 的 DMF 溶液加热至 90-100°C 后，才能将 4 转化回 5。还发现室温下 5 的铜络合物在 CDCl3 中的溶液对于阻转异构化无限期稳定。根据这些数据，现在可以更清楚地揭示这种行为的原因。例如，当 1 转化为 2 时，仅形成 aS-阻转异构体，这在前面通过假设 Cu 以最小化所有非键合相互作用的方式保持两个配体（恶唑啉氮）来解释。此外，2 中芳基-芳基旋转的势垒非常高，因此动力学控制的产物是唯一形成和分离的产物。在本例的萘恶唑啉 3 中，当在吡啶中进行偶联时，我们惊讶地发现 4 而不是 5 才是……
We have been engaged for several years in the acquisition of chiral binaphthyls from the Ullmann coupling of 1-bromo-2-oxazolinylnaphthalenes 11 and 8-bromo-1-oxazolinylnaphthalenes 3. 2 In both cases, the binaphthyl coupling products 2 and 4, respectively, were obtained in high diastereoselectivity (> 99%). 1, 2 In view of the large effort expended by a number of laboratories to utilize chiral binaphthyls, mainly of the type depicted by 2, as chiral catalysts, we have focused our recent attention on the more rarely studied4 1, 1′, 8, 8′-systems, 4. In our recent preliminary report, 2 we showed that the chiral bromo derivative 3 gave, upon heating in refluxing pyridine containing activated copper powder, the single diastereomer (aS, S)-4 which was quite stable to atropisomerism, even after heating for prolonged periods. Surprisingly, heating 4 for 24 h at 145 C gave a mixture of 4 and 5 in a 75: 25 ratio, only to return to 4 upon standing at room temperature. An X-ray structure2 of 4 showed that configuration (Scheme 1, 4A) preferred to have both naphthalene rings at 68 and the oxazolines almost orthoganol to the naphthalenes. The oxazoline rings did not appear to show any rotation about the connecting CC bond (Scheme 1A, bond a), for this would place the tert-butyl groups into the π-face of the naphthalene rings. Since the 3: 1 mixture of 4: 5 returns to> 98% 4 at room temperature, this supports the earlier report5 that the activation barrier to atropisomerization of many 1, 1′, 8, 8′-binaphthyls is rather low. This is especially so when sp2 substituents are present at the 8, 8′ position. The barrier is much higher with sp3 substituents OH and OMe, since they present greater volume during the rotation, and these derivatives have indeed been resolved into enantiomers. 6-8 Fuji4 also reported facile atropisomerization in similar systems containing phosphorus substituents and attributes the behavior to distortion from planarity in the naphthalene rings, which was confirmed by X-ray data. Careful examination of the X-ray structure of 42 showed no such distortion in the naphthalene rings so the stability of 4 as the only atropisomer at room temperature must be due to other factors (vide supra).Although the low barrier to rotation in 4 to 5 may preclude its use as a chiral catalyst, we still felt further study was necessary. We were surprised to learn that when the Ullmann coupling was performed in DMF in place of pyridine, the sole product obtained was the aR-atropisomer 5, with none of the aS-derivative detectable by NMR. 2 When the copper salts were removed on workup, the aR-atropisomer was stable as a crystalline solid at room temperature for several hours and indefinitely at-20 C. However, when dissolved in various solvents at room temperature, it was rapidly and completely transformed back to the aS-isomer 4. Of most interest was the ability to transform 4 back to 5 only after heating a DMF solution to 90-100 C containing 1.0 equiv of CuBr. A solution of the copper complex of 5 in CDCl3 at room temperature was also found to be stable to atropisomerization indefinitely. The reasons for this behavior are now more clearly revealed in light of these data. For example, when 1 was transformed into 2, only the aS-atropisomer was formed, and this was explained earlier1 by assuming the Cu was holding the two ligands (oxazoline nitrogen) in a manner that minimized all nonbonded interactions. Furthermore, the barrier for aryl-aryl rotation in 2 is very high so the kinetically controlled product was the only one formed and isolated. In the present case of naphthyloxazoline 3, when the coupling is carried out in pyridine, we were surprised to find that 4 and not 5 was the …