Surfactant Technology: With New Rules, Designing New Sequences Is Required
Surfactant Technology: With New Rules, Designing New Sequences Is Required
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DOI：
10.1021/acs.oprd.9b00454
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发表时间：
2020-05-15
影响因子：
3.4
通讯作者：
Gallou, Fabrice
中科院分区：
文献类型：
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作者：
Lippincott, Daniel J.;Landstrom, Evan;Gallou, Fabrice
随着水中表面活性剂介导的化学的工具箱的不断增长和按比例放大的转化的数量的增加，已经产生了巨大的学习[例如，参见：Lipshutz，B. H.来;等，The Hydrophobic Effect Applied to Organic Synthesis：Recent Synthetic Chemistry“in Water”.化学-欧洲化学J. 2018，24（26），6672-6695]。这些机会现在存在于少数专家组中，虽然所有细节还远未完全理解或仍在开发中，但在反应过程和合成设计方面已经获得了大量的专门知识。在这里，我们分享一些胶束催化固有的基本原理，并说明他们对一个特别具有挑战性的情况下，涉及铃木宫浦交叉耦合。活性药物成分（API）和中间体的完整结构出于保密原因没有完全公开，但仍然可以用作说明因素的重要性，与有机溶剂中的传统化学不同，这些因素对于成功的结果可能是至关重要的（例如，亲脂性）。用作该讨论的实例的API与大量与联苯阵列的形成以及酰胺和由亲核芳族取代（SNAr）产生的产物的存在相关的其它靶标具有显著的共性。因此，我们希望利用这些先前的学习，现在可以快速地将它们应用于其他几个重要转换的最佳条件的设计。
With a growing toolbox of surfactant-mediated chemistry in water and an increased number of scaled-up transformations has come tremendous learning [for example, see: Lipshutz, B. H.; et al. The Hydrophobic Effect Applied to Organic Synthesis: Recent Synthetic Chemistry "in Water". Chem. - Eur. J. 2018, 24 (26), 6672-6695]. These opportunities now reside within a few expert groups, and while all of the details are far from fully understood or still under development, substantial know-how has been gained in both reaction process and synthesis design. Herein we share some of the fundamental principles inherent to micellar catalysis and illustrate them on a particularly challenging case involving a Suzuki-Miyaura cross-coupling. The complete structures of the active pharmaceutical ingredient (API) and the intermediates are not fully disclosed for confidentiality reasons but can nevertheless serve as illustrative of the importance of factors that, unlike traditional chemistry in organic solvents, can be crucial to a successful outcome (e.g., lipophilicity). The API used as an example for this discussion bears significant commonality with a large number of other targets associated with the formation of a biphenyl array as well as the presence of an amide and products resulting from nucleophilic aromatic substitutions (SNAr). Hence, we look to utilize these prior learnings and can now rapidly apply them to the design of optimal conditions for several other important transformations.