A sequential application of kinetic resolution and polymer-supported scavenging for the isolation of chiral secondary alcohols
A sequential application of kinetic resolution and polymer-supported scavenging for the isolation of chiral secondary alcohols
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DOI：
10.1021/jo010529u
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发表时间：
2001-08-10
影响因子：
3.6
通讯作者：
Janda, KD
中科院分区：
文献类型：
--
作者：
Córdova, A;Tremblay, MR;Janda, KD
对映体纯或对映体富集的有机化合物的制备是非常重要的。1因此，用于对映选择性合成和外消旋体的动力学拆分的化学和生物化学催化剂的开发已经以加速的速度推进。2-4特别地，动力学拆分在不对称合成中是重要的，因为它提供化合物的两种对映体。组合化学、催化抗体、定点诱变和生物催化剂的定向进化等领域的发展推动了化学和生物催化剂的发现和优化。5，6尽管这些技术已经变得非常强大，但催化剂发现过程仍然面临着一个瓶颈，即催化剂选择性和活性的分析和处理。7在动力学拆分的情况下，需要分离产物以分析催化剂活性和选择性。因此，非常需要促进动力学拆分产物的分离而不需要柱色谱的技术。由于手性仲醇在不对称合成中的重要性，通过催化方法制备手性仲醇是一个非常活跃的研究领域。2c可以进行动力学拆分，由此将仲醇的外消旋混合物转化为光学活性产物（例如，酯和剩余的醇），其通常可以通过柱色谱法分离。为了避免需要耗时的柱色谱法，已报道了用琥珀酸酐酯化仲醇，然后进行酸碱萃取。[8]这一原理也被推广到醇转化为硫酸酯的过程中。[9]应当指出，虽然这两种方法很重要，但它们的范围仅限于大规模反应。此外，它们的通用性受到有效酰化剂的选择的阻碍。还报道了通过脂肪酶催化的与聚（乙二醇）（PEG）的酯交换反应的外消旋碳酸三氟乙酯的可溶性聚合物清除方法。10然而，这种方法也有一些局限性。首先，需要接受PEG的独特催化剂。其次，每种新的酰基供体都需要精心设计的合成方案来形成每种活化的碳酸酯。最近，Vedejs报道了在三相条件下进行的平行动力学拆分。在此过程中，一种对映体与聚合物负载的试剂反应，从而能够通过过滤分离对映体。为了补充这些现有的技术，我们提出了一种方法来分离从仲醇的动力学拆分的产物。
The preparation of enantiomerically pure or enantioenriched organic compounds is of great importance. 1 As such, the development of chemical and biochemical catalysts for both enantioselective synthesis and the kinetic resolution of racemates has advanced at an accelerated pace. 2-4 In particular, kinetic resolution is important in asymmetric synthesis since it provides both enantiomers of a compound. Developments in the areas of combinatorial chemistry, catalytic antibodies, sitedirected mutagenesis, and directed evolution of biocatalysts have fueled the discovery and optimization of both chemical and biological catalysts. 5, 6 As powerful as these technologies have become, the catalyst discovery process still faces a bottleneck centered around the analysis and processing of both catalyst selectivity and activity. 7 In the case of kinetic resolution, the products need to be separated to enable analysis of catalyst activity and selectivity. Therefore, techniques that facilitate the separation of kinetic resolution products without the need for column chromatography are highly desirable. The preparation of chiral sec-alcohols by catalytic processes is a very active area of research because of their importance as building blocks in asymmetric synthesis. 2c Kinetic resolution can be performed whereby a racemic mixture of sec-alcohols is transformed into optically active products (eg, an ester and remaining alcohol) that can be separated typically by column chromatography. To circumvent the need for time-consuming column chromatography, esterification of sec-alcohols with succinic anhydride followed by an acid-base extraction has been reported. 8 This principle has also been extended to the conversion of alcohols to sulfate esters. 9 It should be noted that while these two methods are important, their scope is limited to large-scale reactions. Furthermore, their generality is hampered by the choice of effective acylating agents. A soluble polymer scavenging approach of a racemic trifluoroethyl carbonate through lipase-catalyzed transesterification with poly (ethylene glycol)(PEG) has also been reported. 10 However, this methodology also presents several limitations. First, a unique catalyst accepting PEG is needed. Second, an elaborate synthetic scheme to form each activated carbonate is required for each new acyl donor. More recently, Vedejs has reported a parallel kinetic resolution performed under triphasic conditions. 11 During this process, one of the enantiomers reacts with a polymer-supported reagent enabling separation of the enantiomers by filtration. To complement these existing technologies, we present a method to separate the products from the kinetic resolution of sec-alcohols.