Silver-Mediated Direct Amination of Benzoxazoles: Tuning the Amino Group Source from Formamides to Parent Amines
Silver-Mediated Direct Amination of Benzoxazoles: Tuning the Amino Group Source from Formamides to Parent Amines
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DOI：
10.1002/anie.200903957
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Chang, Sukbok
中科院分区：
文献类型：
--
作者：
Cho, Seung Hwan;Kim, Ji Young;Chang, Sukbok
杂环化合物的C？N键的构建是合成化学中非常重要的转变，因为它可以提供生物、医药和材料科学中非常感兴趣的含氮分子。[1]在过去的几十年里，金属促进的C？N键的形成反应已经取得了显著的进展，如双键或三键的氢胺化[2]或氧化酰胺化[3]以及Buchwald-Hartwigtype交叉偶联。[4]尽管有这些重大的进展，在芳基或烷基C？H键上直接安装氨基或它们的替代物仍然是具有挑战性的。为了满足这一需求，人们广泛研究了一种新的方法，即在碳氢化合物中氧化加成氨基或氨基。特别是最近开发了通过催化C±H键活化来对预组织芳烃进行位置选择性胺化的方法。[6]还报道了通过双取代肼的热裂解来邻位选择性胺化萘酚。[7]最近，Mori和他的同事报道了在高温(%1408C)下使用铜盐对氮唑进行氧化胺化反应。[8]在这里，我们描述了一种前所未有的银介导苯并恶唑的C±N键的生成。基于机理上的考虑，我们还开发了一种在非常温和的反应条件下与母胺直接胺化的协议。[9]与我们最近在金属催化的C±H键功能化方面所做的努力相一致，[10]我们想知道在甲酰胺存在下，富电子杂芳烃在Pd/Ag-催化体系中是否可以得到酰胺化产物(方案1)。[11]令我们惊讶的是，当苯并恶唑(1a)在有醋酸添加剂的情况下与N，N-二甲基甲酰胺(DMF)在Pd-(OAc)2/Ag2CO3体系中反应时，得到了单一的产物2-胺基苯并恶唑2a尽管收益率适中。相反，在所考察的其他反应条件下没有观察到酰胺化产物3a。[12]随后的研究表明，即使在没有钯催化剂的情况下，意外的脱羰胺化反应也能以略高的产率进行。受这些初步结果的鼓舞，我们随后尝试在整齐的DMF(40当量)中使用苯并恶唑(1a)来优化脱羰胺化反应条件，如表1所示。尽管在没有银盐或酸性添加剂的情况下没有得到所需的产物(条目1和条目2)，在银盐存在下，添加某些类型的羧酸可促进转化(条目3-8)。[14]在所考察的各种酸中，对茴香酸被证明对胺化反应最有效(条目8)。催化量的Ag2CO3没有提供所需的产物(条目9)，因此表明在这些反应条件下使用化学计量数量的银盐对于顺利转化是必不可少的。此外，其他银源，如Ag2O、AgOAc、AgOTf(Tf=三氟酸盐)或AGF(条目10)与Ag2CO3相比效率较低[13]。
The construction of CÀN bonds of heteroaromatic compounds is a highly important transformation in synthetic chemistry since it can offer nitrogen-containing molecules of great interest in biological, pharmaceutical, and materials sciences.[1] During the past decades, remarkable progresses have been made in the metal-facilitated CÀN bond-forming reactions such as hydroamination [2] or oxidative amidation [3] of double or triple bonds as well as the Buchwald–Hartwigtype cross couplings.[4] Despite these significant advances, direct installation of amino groups or their surrogates on aryl or alkyl CÀH bonds is still challenging. To meet this demand, a new approach involving oxidative addition of amino or amido moieties into hydrocarbons has been extensively studied.[5, 6] In particular, site-selective amination of preorganized arenes through catalytic CÀH bond activation was recently developed.[6] An ortho-selective amination of naphthols through thermal cleavage of disubstituted hydrazines was also reported.[7] Most recently, Mori and co-workers have reported an oxidative amination of azoles using copper salts at high temperature (% 1408C).[8] Herein, we describe an unprecedented silver-mediated CÀN bond formation of benzoxazoles by decarbonylative coupling with formamides. On the basis of mechanistic considerations, we have also developed a direct amination protocol with parent amines under very mild reaction conditions.[9] In line with our recent efforts on metal-catalyzed CÀH bond functionalization,[10] we wondered whether subjection of electron-rich heteroarenes to Pd/Ag-catalytic systems in the presence of formamides could provide amidated products (Scheme 1).[11] To our surprise, when benzoxazole (1a) was treated with N, N-dimethylformamide (DMF) using the Pd-(OAc) 2/Ag2CO3 system in the presence of an acetic acid additive, 2-aminated benzoxazole 2a was obtained as a single product, albeit in moderate yield. In contrast, no amidated product 3a was observed under other reaction conditions examined.[12] Subsequent studies revealed that the unexpected decarbonylative amination reaction also proceeded even in the absence of the palladium catalyst and with slightly higher yields.Encouraged by these preliminary result, we subsequently tried to optimize the decarbonylative amination conditions using benzoxazole (1a) in neat DMF (40 equiv),[13] as shown in Table 1. Although no desired product was obtained in the absence of the silver salt or the acid additives (entries 1 and 2), addition of certain types of carboxylic acids promoted the transformation in the presence of silver salts (entries 3–8).[14] Among various acids examined, p-anisic acid turned out to be most effective for the amination reaction (entry 8). Catalytic amounts of Ag2CO3 did not furnish the desired product (entry9), thus indicating that the use of stoichiometric amounts of silver salts is essential for smooth conversion under these reaction conditions.[15] In addition, other silver sources such as Ag2O, AgOAc, AgOTf (Tf= triflate), or AgF (entry 10) were less effective when compared to Ag2CO3.[13]