Hari Durga Prasad, Caramenti Paola, Waser Jerome
Laboratory of Catalysis and Organic Synthesis , Ecole Polytechnique Fédérale de Lausanne , EPFL SB ISIC LCSO, BCH 4306, 1015 Lausanne , Switzerland.
Acc Chem Res. 2018 Dec 18;51(12):3212-3225. doi: 10.1021/acs.accounts.8b00468. Epub 2018 Nov 28.
The efficient synthesis of organic compounds is an important field of research, which sets the basis for numerous applications in medicine or materials science. Based on the polarity induced by functional groups, logical bond disconnections can be deduced for the elaboration of organic compounds. Nevertheless, this classical approach makes synthesis rigid, as not all bond disconnections are possible. The concept of Umpolung has been therefore introduced: by inverting the normal polarity of functional groups, new disconnections become possible. Among the tools for achieving Umpolung, hypervalent iodine reagents occupy a privileged position. The electrophilicity of the iodine atom and the reactivity of the hypervalent bond allow access to electrophilic synthons starting from nucleophiles. Nevertheless, some classes of hypervalent iodine reagents can be too unstable for many applications, in particular involving metal catalysis. In this context, cyclic hypervalent iodine reagents, especially benziodoxolones (BXs), have been known for a long time to be more stable than their acyclic counterparts, yet their synthetic potential had not been fully exploited. In this Account, we report our efforts since 2008 on the use of BX reagents in the development of new transformations in organic synthesis, which showed for the first time their versatility as synthetic tools. Our work started with electrophilic alkynylation, as alkynes are one of the most important functional groups in organic chemistry, but are usually introduced as nucleophiles. We used ethynylbenziodoxolones (EBXs) in the direct alkynylation of nucleophiles, such as keto esters, thiols, or phosphines. The reagents could then be applied to the gold- and palladium-catalyzed alkynylation of C-H bonds on (hetero)arenes, leading to a more efficient alternative to the Sonogashira reaction. More complex reactions were then developed with formations of several bonds in a single transformation. Gold- and platinum-catalyzed cyclization/alkynylation domino processes gave access to new types of alkynylated heterocycles. Multifunctionalization of olefins became possible through intramolecular oxy- and amino-alkynylations. (Enantioselective) copper-catalyzed oxy-alkynylation of diazo compounds led to stereocenters with perfect atom economy. Finally, EBXs were also used for the alkynylation of radicals generated under photoredox conditions. Since 2013, we then extended the use of BX reagents to other transformations. Azidobenziodoxol(on)ess (ABXs) were used in the azidation of keto esters, enol silanes, and styrenes. New more stable derivatives were introduced. Cyanobenziodoxolones (CBXs) enabled the cyanation of stabilized enolates, thiols, and radicals. Finally, new BX reagents were developed for the Umpolung of indoles and pyrroles. They could be used in metal-catalyzed directed C-H functionalizations, as well as in Lewis acid mediated oxidative coupling to give functionalized bi(hetero)arenes. In the past decade, our group and others have shown that BX reagents are not only "structural beauties", but also extremely useful reagents in synthetic chemistry. A toolbox of cyclic hypervalent iodine reagents is now available to achieve Umpolung-based disconnections. We are convinced that the field is still in its infancy, and many new reagents and transformations still remain to be discovered.
有机化合物的高效合成是一个重要的研究领域，它为医学或材料科学中的众多应用奠定了基础。基于官能团诱导的极性，可以推导出用于有机化合物合成的合理键切断方式。然而，这种经典方法使得合成过程具有局限性，因为并非所有的键切断都是可行的。因此，极性翻转（Umpolung）的概念被引入：通过反转官能团的正常极性，新的切断方式成为可能。在实现极性翻转的工具中，高价碘试剂占据着特殊的地位。碘原子的亲电性和高价键的反应活性使得从亲核试剂出发能够获得亲电合成子。然而，某些类型的高价碘试剂对于许多应用来说可能过于不稳定，特别是涉及金属催化的应用。在这种情况下，环状高价碘试剂，尤其是苯并碘恶唑酮（BXs），长期以来一直被认为比它们的非环状同类物更稳定，但其合成潜力尚未得到充分开发。在这篇综述中，我们报告了自2008年以来我们在有机合成新转化中使用BX试剂的研究成果，首次展示了它们作为合成工具的多功能性。我们的工作始于亲电炔基化反应，因为炔烃是有机化学中最重要的官能团之一，但通常作为亲核试剂引入。我们使用乙炔基苯并碘恶唑酮（EBXs）对亲核试剂进行直接炔基化反应，如酮酯、硫醇或膦。这些试剂随后可应用于金和钯催化的（杂）芳烃上C-H键的炔基化反应，为Sonogashira反应提供了一种更有效的替代方法。随后开发了更复杂的反应，在单一转化中形成多个键。金和铂催化的环化/炔基化多米诺过程产生了新型的炔基化杂环化合物。通过分子内氧-和氨基-炔基化反应实现了烯烃的多官能化。（对映选择性）铜催化的重氮化合物的氧-炔基化反应以完美的原子经济性生成了立体中心。最后，EBXs还用于光氧化还原条件下产生的自由基的炔基化反应。自2013年以来，我们将BX试剂的使用扩展到了其他转化反应。叠氮基苯并碘恶唑酮（ABXs）用于酮酯、烯醇硅烷和苯乙烯的叠氮化反应。引入了更稳定的新衍生物。氰基苯并碘恶唑酮（CBXs）实现了稳定烯醇盐、硫醇和自由基的氰化反应。最后，开发了用于吲哚和吡咯极性翻转的新型BX试剂。它们可用于金属催化的定向C-H官能化反应，以及路易斯酸介导的氧化偶联反应，以生成官能化的双（杂）芳烃。在过去十年中，我们小组和其他研究团队表明，BX试剂不仅是“结构优美的化合物”，而且是合成化学中极其有用的试剂。现在有一个环状高价碘试剂工具箱可用于实现基于极性翻转的切断。我们相信该领域仍处于起步阶段，许多新的试剂和转化反应有待发现。
