Gao Detian, Zhai Huimin, Parvez Masood, Back Thomas G
Department of Chemistry, University of Calgary, Calgary, AB, Canada, T2N 1N4.
J Org Chem. 2008 Oct 17;73(20):8057-68. doi: 10.1021/jo801621d. Epub 2008 Sep 18.
Several representative acetylenic sulfones were immobilized on a polymer support derived from Merrifield resin by means of ester linkers that were used to couple free carboxylic acid groups on the solid support with benzylic hydroxyl functions on the arylsulfonyl moieties of the acetylenes. Several examples of reversed ester linkers, using Merrifield resin directly, were also successfully prepared. The 1,3-dipolar cycloadditions of the solid-supported acetylenic sulfones were investigated with a series of 1,3-dipoles, including benzyl azide, ethyl diazoacetate, diazomethane, as well as representative nitrile oxides, nitrile imines, nitrile ylides, nitrones, azomethine imines, azomethine ylides, munchnones, and sydnones. In general, analogous cycloadditions were also performed with acetylenic sulfones in solution phase for comparison. The cycloadditions typically afforded good to excellent yields of the desired products in both solution and solid phase, although the latter reactions sometimes required more vigorous conditions. Except in the case of benzyl azide and diazo compounds, where mixtures of regioisomers were obtained, the other 1,3-dipoles reacted with high regioselectivity and afforded essentially unique regioisomers. Cleavage of the products from the resin was smoothly effected by alkaline hydrolysis, while several attempts at reductive desulfonylation with sodium amalgam or samarium diiodide-HMPA resulted in N-O or C-O scission, in addition to cleavage from the polymer. The method provides access to a number of important classes of heterocycles, including variously substituted and functionalized triazoles, pyrazoles, 1,2-oxazoles, pyrroles, as well as their dihydro and bicyclic analogues. The success of the cycloadditions on polymer supports paves the way to future investigations of sequential transformations leading to libraries of useful heterocycles.
通过酯连接基将几种具有代表性的炔基砜固定在由Merrifield树脂衍生的聚合物载体上，这些酯连接基用于将固体载体上的游离羧酸基团与乙炔芳基磺酰基部分上的苄基羟基官能团偶联。还成功制备了几个直接使用Merrifield树脂的反向酯连接基的实例。研究了固体负载的炔基砜与一系列1,3 - 偶极体的1,3 - 偶极环加成反应，这些偶极体包括苄基叠氮、重氮乙酸乙酯、重氮甲烷，以及代表性的腈氧化物、腈亚胺、腈叶立德、硝酮、甲亚胺亚胺、甲亚胺叶立德、慕尼黑酮和斯德酮。一般来说，为了进行比较，也在溶液相中用炔基砜进行了类似的环加成反应。环加成反应通常在溶液相和固相中都能得到良好至优异产率的所需产物，尽管后者的反应有时需要更剧烈的条件。除了苄基叠氮和重氮化合物的情况会得到区域异构体混合物外，其他1,3 - 偶极体以高区域选择性反应并基本上得到单一的区域异构体。通过碱性水解可顺利实现产物从树脂上的裂解，而用钠汞齐或二碘化钐 - HMPA进行还原脱磺酰化的几次尝试，除了使产物从聚合物上裂解外，还导致了N - O或C - O键的断裂。该方法可用于制备多种重要类型的杂环化合物，包括各种取代和官能化的三唑、吡唑、1,2 - 恶唑、吡咯，以及它们的二氢和双环类似物。在聚合物载体上进行环加成反应的成功为未来研究导致有用杂环化合物库的连续转化铺平了道路。
