Catalyst-Directed Diastereoselective Isomerization of Allylic Alcohols for the Stereoselective Construction of C(20) in Steroid Side Chains: Scope and Topological Diversification,Journal of the American Chemical Society

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Catalyst-Directed Diastereoselective Isomerization of Allylic Alcohols for the Stereoselective Construction of C(20) in Steroid Side Chains: Scope and Topological Diversification
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2015-08-11 , DOI: 10.1021/jacs.5b06281
Houhua Li ₁ , Clément Mazet ₁

Affiliation

The stereoselective construction of C20 in steroidal derivatives by a highly diastereoselective Ir-catalyzed isomerization of primary allylic alcohols is reported. A key aspect of this strategy is a straightforward access to geometrically pure steroidal enol tosylate and enol triflate intermediates for subsequent high yielding stereoretentive Negishi cross-coupling reactions to allow structural diversity to be introduced. A range of allylic alcohols participates in the diastereoselective isomerization under the optimized reaction conditions. Electron-rich and electron-poor aryl or heteroaryl substituents are particularly well-tolerated, and the stereospecific nature of the reaction provides indifferently access to the natural C20-(R) and unnatural C20-(S) configurations. Alkyl containing substrates are more challenging as they affect regioselectivity of iridium-hydride insertion. A rationale for the high diastereoselectivities observed is proposed for aryl containing precursors. The scope of our method is further highlighted through topological diversification in the side chain and within the polycyclic domain of advanced and complex steroidal architectures. These findings have the potential to greatly simplify access to epimeric structural analogues of important steroid scaffolds for applications in biological, pharmaceutical, and medical sciences.

中文翻译：

用于立体选择性构建类固醇侧链中 C(20) 的烯丙醇的催化剂定向非对映选择性异构化：范围和拓扑多样化

报道了通过高度非对映选择性 Ir 催化异构化伯烯丙醇在甾体衍生物中立体选择性构建 C20。该策略的一个关键方面是直接获得几何纯甾体烯醇甲苯磺酸酯和烯醇三氟甲磺酸酯中间体，用于随后的高产立体保留 Negishi 交叉偶联反应，以引入结构多样性。一系列烯丙醇在优化的反应条件下参与非对映选择性异构化。富电子和缺电子的芳基或杂芳基取代基的耐受性特别好，反应的立体定向特性提供了对天然 C20-(R) 和非天然 C20-(S) 构型的无差别访问。含烷基的底物更具挑战性，因为它们会影响氢化铱插入的区域选择性。对于含芳基的前体，提出了观察到的高非对映选择性的基本原理。我们方法的范围通过侧链中和高级和复杂甾体结构的多环域内的拓扑多样化得到进一步突出。这些发现有可能大大简化对重要类固醇支架的差向异构结构类似物的获取，以用于生物、制药和医学科学。我们方法的范围通过侧链中和高级和复杂甾体结构的多环域内的拓扑多样化得到进一步突出。这些发现有可能大大简化对重要类固醇支架的差向异构结构类似物的获取，以用于生物、制药和医学科学。我们方法的范围通过侧链中和高级和复杂甾体结构的多环域内的拓扑多样化得到进一步突出。这些发现有可能大大简化对重要类固醇支架的差向异构结构类似物的获取，以用于生物、制药和医学科学。

更新日期：2015-08-11

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