A Solid-Supported Organocatalyst for Highly Stereoselective, Batch, and Continuous-Flow Mannich Reactions
A Solid-Supported Organocatalyst for Highly Stereoselective, Batch, and Continuous-Flow Mannich Reactions
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DOI：
10.1002/chem.200901310
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发表时间：
2009-01-01
影响因子：
4.3
通讯作者：
Pericas, Miquel A.
中科院分区：
文献类型：
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作者：
Alza, Esther;Rodriguez-Escrich, Carles;Pericas, Miquel A.
在聚苯乙烯催化下，醛和酮与N-(对甲氧基苯基)乙氧基亚胺的快速和高立体选择性的Mannich反应。报道了用(2SAR)-羟基脯氨酸功能化的树脂。研究了连接脯氨酸和聚合物主链的连接剂的性质对反应的影响，结果表明1，2，3-三氮唑连接物具有最好的催化活性和对映体选择性。和乙醛捐赠者。在DMF-Willi-酮供体中记录了在1-3h内导致完全转化的快速反应。反应往往较慢，但可以通过低功率的微波辐射有效地加速(六元环烷酮)。这种方法极大地促进了产品的分离，因为只需简单的过滤就可以除去催化剂。允许在连续流动中实现醛基物的反应。用这种方法，在室温下实现了对映和非对映纯加合物(Synlann&Gt；97：3：EE>；99%)的连续合成，停留时间为6.0 mm。这种方法允许通过使用046 mmo1的催化树脂(5.9mol%)来制备高达7.8 mmo1的Mannich加合物，大大简化了实验方案，避免了纯化步骤
The fast and highly stereoselective Mannich reaction of aldehydes and ketones with the N-(p-methoxyphenyl) ethyl glyoxylate imine catalyzed by polystyrene. resins functionalized with (2SAR)-hydroxyproline is reported The effect of the nature of the linker connecting proline with the polymeric backbone has been studied, and a 1,2,3-triazole linker constructed front azidomethyl polystyrene and O-propargyl hydroxyproline turns out to be optimal for catalytic activity and enantioselectivity. With aldehyde donors. fast reactions leading to complete con-version in 1-3 h are recorded in DMF Willi ketone donors. the reactions tend to be slower, but can be efficiently accelerated (six-membered ring cycloalkanones) by low-power microwave irradiation. This approach, which greatly facilitates product isolation since the catalyst is removed by simple filtration. has allowed the implementation of the reactions of aldehyde Substrates in a continuous-flow. single-pass system In this manner, the Continuous synthesis of the enantiomerically and diastereomerically pure adducts (synlann > 97:3: ee>99%) has been achieved at room temperature with residence times of 6.0 mm. This methodology has allowed for the preparation of up to 7.8 mmol elf the desired Mannich adduct through the use of 046 mmol of catalytic resin (5 9 mol%), in at greatly simplified experimental protocol that avoids purification steps