Asymmetric catalysis: Resin-bound hydroxyprolylthreonine derivatives in enamine-mediated reactions
Asymmetric catalysis: Resin-bound hydroxyprolylthreonine derivatives in enamine-mediated reactions
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DOI：
10.1002/anie.200801811
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Kurth, Mark J.
中科院分区：
文献类型：
--
作者：
Carpenter, Richard D.;Fettinger, James C.;Kurth, Mark J.
用阶梯经济控制相对立体化学和绝对立体化学[1,2]是有机合成领域不断面临的挑战不对称交叉醛历来涉及手性助剂或o捕获的有机金属中间体；后者要么是齐默尔曼-特拉克斯勒模型，要么是开放过渡状态模型然而，助剂延长了合成，有机金属通常需要仔细控制反应条件和有限的官能团耐受性。然而，胺主要在c端反应，通常在环境反应条件下产生产物c2对称反式- 2,5 -二甲基吡咯烷试剂用于不对称烯胺反应。然而，它的疗效差，稀缺。尽管存在几种不对称合成方法来制备该试剂，但其有限的商业可用性表明，这些冗长的工艺并没有影响供应脯氨酸衍生的有机催化剂在一定程度上缓解了这一问题，近年来对脯氨酸衍生的有机催化剂进行了深入的研究，并在Yamamoto[7]和Miller.[8]等人的报告中进行了讨论本文综述了负载型（杂均型）[9]和非负载型[10]有机催化剂的反应。当应用于醛缩缩合时，多相负载的有机催化剂通常需要高催化剂负载[11]和长反应时间[12]，同时提供不同的对映选择性。[11-13]非负载型有机催化剂通常需要较长的反应时间，[14]对溶剂有严格的要求，[15]产率多变
Control of relative and absolute stereochemistry with stepeconomy [1, 2] presents a continuing challenge in organic synthesis.[3] Asymmetric crossed aldols have historically involved chiral auxiliaries or O-trapped organometallic intermediates; the latter operate by either a Zimmerman–Traxler or an open transition-state model.[4] However, auxiliaries lengthen syntheses, and organometallics typically require careful control of reaction conditions and have limited functional-group tolerance. Enamines, however, predominantly react at the C-terminus, and generally deliver products under ambient reaction conditions.[3] The C2-symmetric trans-2, 5-dimethylpyrrolidine reagent is used in asymmetric enamine reactions. However, it suffers from poor efficacy and is scarce. Although several asymmetric syntheses exist for the preparation of this reagent,[5] its limited commercial availability suggests that these lengthy protocols have not impacted supply.[6] This problem has been somewhat alleviated by prolinederived organocatalysts, which have been under intense investigation in recent years and discussed in reports from the groups of Yamamoto [7] and Miller.[8] Reactions of supported (both hetero-and homogeneous)[9] and nonsupported [10] organocatalysts have been reviewed. When applied to aldol condensations, heterogeneous supported organocatalysts often require high catalyst loading [11] and long reaction times,[12] while delivering varied enantioselectivities.[11–13] Non-supported organocatalysts often require extended reaction times,[14] have strict solvent requirements,[15] and produce variable yields.[16]