Metal-Free, Aerobic Dioxygenation of Alkenes Using Hydroxamic Acids
Metal-Free, Aerobic Dioxygenation of Alkenes Using Hydroxamic Acids
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DOI：
10.1002/anie.201000843
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发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Alexanian, Erik J.
中科院分区：
文献类型：
--
作者：
Schmidt, Valerie A.;Alexanian, Erik J.
用于实现烯烃的邻位双官能化的方法极大地促进了官能化有机化合物的制备。有用的转化的例子包括烯烃双氧化，[1]氨基氧化，[2]和二氨基化，[3]最近有许多值得注意的发展采用钯催化。这些方法的一个共同缺点是使用贵重和/或有毒的过渡金属催化剂。我们在此报道了一种方便的、通用的烯烃双氧化方法，该方法利用氧气作为环境友好且廉价的氧化剂，同时避免使用金属催化剂。作为一个稳定的三重态双自由基在其基态，分子氧反应迅速与碳中心的自由基。[4]Gomberg在他对第一个有机自由基三苯基甲基的历史性研究中见证了这种反应模式，[5]并且是经典自由基自氧化的重要步骤。[6]自由基氧化在现代有机合成中已被证明是有价值的，特别是在碳中心自由基的生成以区域选择性方式进行的情况下。例如，自由基脱羧[7]、脱卤[8]、脱汞[9]和碳环化[10]过程都利用分子氧来选择性地递送自由基氧化产物。在他们对氨羟自由基与烯烃的基本反应性的开创性工作中，Perkins和同事观察到一个氨羟自由基环化然后氧化的单一显着例子（方案1）。[11]在试图制备高度共轭的二苯乙烯取代的叔丁基氨酰自由基2时，母体异羟肟酸1经历自发氧化和分子内环化，然后自由基氧化以提供作为非对映体混合物的氢过氧化物3。[12]这些含有吸电子酰基的硝酰基自由基相对于持久的二烷基硝酰基自由基（例如克里思，2，2，6，6-四甲基哌啶1-氧基）是不稳定的，[13]并且可以通过在温和条件下氧化N-芳基或烷基异羟肟酸产生。[14]我们设想了一种烯烃环化与拴amidoxyl自由基，形成原位从容易获得的N-芳基异羟肟酸，随后与分子氧反应，作为一个潜在的一般方法的烯烃的二氧化（方案2）。这种策略利用amidoxyl自由基作为高度反应性的烷氧基自由基的替代物，[15]并允许通过随后容易的还原裂解NH 4 O键来产生邻位二醇。此外，该方法区分了递送至烯烃的氧原子官能度，这是使用当前的双氧化方法难以实现的。
Methods for achieving the vicinal difunctionalization of alkenes greatly facilitate the preparation of functionalized organic compounds. Examples of useful transformations include alkene dioxygenations,[1] aminooxidations,[2] and diaminations,[3] with many notable recent developments employing palladium catalysis. A common drawback to these processes is the use of precious and/or toxic transition-metal catalysts. We report herein a convenient, general method for alkene dioxygenation that utilizes oxygen as an environmentally friendly and inexpensive oxidant, while circumventing the use of metal catalysts. As a persistent triplet diradical in its ground state, molecular oxygen reacts rapidly with carbon-centered radicals.[4] This mode of reactivity was witnessed by Gomberg during his historic studies on the first organic free radical, triphenylmethyl,[5] and is an important step in classical radical autoxidation.[6] Radical oxygenation has proven to be of value in modern organic synthesis, especially in cases where the generation of carbon-centered radicals proceeds in a regioselective manner. For example, radical decarboxylation,[7] dehalogenation,[8] demercuration,[9] and carbocyclization [10] processes have all utilized molecular oxygen to selectively deliver radical oxidation products. During their pioneering work on the fundamental reactivity of amidoxyl radicals with alkenes, Perkins and coworkers observed a single remarkable example of an amidoxyl radical cyclization followed by oxygenation (Scheme 1).[11] While attempting to prepare the highly conjugated stilbene-substituted tert-butyl amidoxyl radical 2, the parent hydroxamic acid 1 underwent spontaneous oxidation and intramolecular cyclization followed by radical oxygenation to deliver hydroperoxide 3 as a mixture of diastereomers.[12] These nitroxyl radicals, which contain electronwithdrawing acyl groups, are destabilized relative to persistent dialkyl nitroxyl radicals (eg TEMPO, 2, 2, 6, 6-tetramethylpiperidine 1-oxyl),[13] and can be generated by oxidation of N-aryl or alkyl hydroxamic acids under mild conditions.[14] We envisioned an alkene cyclization with a tethered amidoxyl radical that is formed in situ from readily obtainedN-aryl hydroxamic acids, and subsequent reaction with molecular oxygen, as a potentially general approach to the dioxygenation of alkenes (Scheme 2). This strategy utilizes amidoxyl radicals as a substitute for highly reactive alkoxy radicals,[15] and allows the production of vicinal diols by subsequent facile reductive cleavage of the NÀO bond. Furthermore, this method differentiates the oxygen atom functionality delivered to the alkene, which is difficult using current dioxygenation methods.