Non-C2-symmetric, chirally economical, and readily tunable linked-binols: design and application in a direct catalytic asymmetric mannich-type reaction.
Non-C2-symmetric, chirally economical, and readily tunable linked-binols: design and application in a direct catalytic asymmetric mannich-type reaction.
复制标题
DOI：
10.1002/anie.200500425
复制
发表时间：
2005-05
影响因子：
--
通讯作者：
Takamasa Yoshida;H. Morimoto;N. Kumagai;S. Matsunaga;M. Shibasaki
中科院分区：
文献类型：
--
作者：
Takamasa Yoshida;H. Morimoto;N. Kumagai;S. Matsunaga;M. Shibasaki
安徽3537号。化学。2005,117,3536-3540 ww.安格万特。De 2005 Wiley-VCH Verlag GmbH&Co.KGaA，Weinheim ee值(68小时，24%ee；条目2)。配体3a缺少一个酚羟基，得到的结果与1a的结果相似(条目3)。具有异构体双酚单元的配体3b也是有效的(条目4)，因此表明双酚单元的手性是由与锌中心的络合控制的。[14]即使是无手性单元，如3c，也有很好的结果(1h，99%产率，99%ee；条目5)，而在2о-位具有酚羟基的配体3d反应速率低，对映体选择性差(23h，74%产率，9%ee；条目6)。配体3e和3f也产生了不令人满意的产率和适度的对映选择性(条目7和8)。条目5-8所示的结果表明，芳环上适当位置的酚羟基和取代基都是必需的。为了评价取代基对苯酚环的影响，使用了配体3G-k，它们都表现出高的反应活性和对映体选择性(条目9-15)。配体3i-k中的非手性单元很容易从商业上可获得的水杨醛衍生物中获得。[15]尽管方案3中的许多配体具有高的对映体选择性(表1)，但很难从反应速率的角度精确地比较它们的性能。通常，由于底物溶解度的限制，当催化剂负载量降至0.1摩尔%时，催化剂浓度会变得相当低。因此，需要在稀薄条件下有较高的循环频率(TOF)和循环次数(TON)来降低催化剂的负载量。为了定量评价配体，在稀释条件下([亚胺]=31 mM，[3]=0.31 mM，1摩尔%；表2
3537 Angew. Chem. 2005, 117, 3536–3540 www. angewandte. de 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim ee value (68 h, 24% ee; entry 2). Ligand 3a, which lacks one phenolic OH group, gave results similar to those obtained with 1a (entry 3). Ligand 3b with an atropisomeric biphenol unit was also efficient (entry4), thus suggesting that the chirality of the biphenol unit was controlled by complexation with the zinc center.[14] Even an achiral unit, such as 3c, gave excellent results (1 h, 99% yield, 99% ee; entry 5), whereas ligand 3d, which has a phenolic OH group in the 2о-position, had a low reaction rate and poor enantioselectivity (23 h, 74% yield, 9% ee; entry 6). Ligands 3e and 3 f also produced unsatisfactory yields and modest enantioselectivities (entries 7 and 8). The results shown in entries 5–8 imply that both the phenolic OH group at the proper position and a substituent on the aromatic ring are required. To evaluate the effects of substituents on the phenol ring, ligands 3g–k were used, and all of them showed a high reactivity and enantioselectivity (entries 9–15). The achiral units in ligands 3i–k were readily accessible from commercially available salicylic aldehyde derivatives.[15]Although many ligands in Scheme 3 gave high enantioselectivities (Table 1), it was difficult to compare their performance precisely in terms of reaction rate. Generally, catalyst concentration becomes rather low when catalyst loading is reduced to< 0.1 mol% because of substrate-solubility limitations. Thus, high turnover frequencies (TOF) and turnover numbers (TON) under dilute conditions are required to lower the catalyst loading. To evaluate the ligands quantitatively, the reaction for each ligand was monitored under dilute conditions ([imine]= 31 mm,[3]= 0.31 mm, 1 mol%; Table 2