Palladium-catalyzed alpha-arylation of ketones
Palladium-catalyzed alpha-arylation of ketones
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DOI：
10.1021/ja972593s
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发表时间：
1997-11-12
影响因子：
15
通讯作者：
Buchwald, SL
中科院分区：
文献类型：
--
作者：
Palucki, M;Buchwald, SL
在过去的二十年里，R-芳基酮的合成受到了广泛的关注。1许多化学计量的芳基化试剂已成功地开发用于此目的;然而，它们的效用降低，因为R-芳基酮的每次合成需要合成不同的芳基化试剂。2，3相反，芳基卤化物与酮的直接偶联将提供用于合成R-芳基酮的方便方法。Semmelhack等人已经证明，Ni（COD）2（COD）环辛烷催化芳基碘与酮烯醇化物的分子内偶联。4虽然有Pd或Ni催化的分子间偶联反应的报道，得到R-芳基酮，这些方法需要使用化学计量的锡试剂和/或使用烯醇醚、烯胺或R-氯酮衍生物代替酮。5，6因此，尚未实现利用容易获得的起始材料并以高区域选择性提供产物的通用方法。在此，我们描述了一种新的钯催化的方法，用于芳基卤与酮的直接交叉偶联。我们先前已经表明，Pd 2（dba）3（dba）二亚苄基丙酮）和Tol-BINAP的混合物催化醇钠（通过醇与NaH的反应原位产生）与缺电子芳基溴的偶联以形成芳基醚。7此外，我们发现，电子中性或富电子的芳基溴化物与醇钠（由伯醇或仲醇产生）的反应提供了还原的芳烃作为主要产物，伴随着醇氧化成相应的酮。正是在后一项研究中，我们意外地观察到少量的R-芳基酮产物。例如，尝试的Pd催化的1-溴-4-叔丁基苯与环己醇的偶联的粗反应混合物的GC分析显示叔丁基苯是主要产物，沿着少量的2-（4-叔丁基苯基）环己酮（2%），方案1。8.认识到需要一种通用的方法来合成
The synthesis of R-aryl ketones has received much attention over the past two decades. 1 A number of stoichiometric arylating reagents have been successfully developed for this purpose; however, their utility is decreased because each synthesis of an R-aryl ketone requires the synthesis of a different arylating reagent. 2, 3 In contrast, the direct coupling of aryl halides with ketones would provide a convenient method for the synthesis of R-aryl ketones. Semmelhack et al. have demonstrated that Ni (COD) 2 (COD) cyclooctadiene) catalyzes the intramolecular coupling of an aryl iodide with a ketone enolate. 4 While there are reports of Pd-or Ni-catalyzed intermolecular coupling reactions that afford R-aryl ketones, these methods require the use of stoichiometric amounts of tin reagents and/or the use of enol ether, enamine, or R-chloro ketone derivatives instead of the ketone. 5, 6 Thus, a general method which utilizes readily available starting materials and affords products in high regioselectivity has not been realized. Herein, we describe a novel Pd-catalyzed method for the direct cross coupling of aryl halides with ketones. We have previously shown that a mixture of Pd2 (dba) 3 (dba) dibenzylidene acetone) and Tol-BINAP catalyzes the coupling of sodium alkoxides (generated in situ by reaction of the alcohol with NaH) with electron-deficient aryl bromides to form aryl ethers. 7 In addition, we found that reaction of electron neutral or electron-rich aryl bromides with sodium alkoxides (generated from primary or secondary alcohols) provides the reduced arene as the major product with concomitant oxidation of the alcohol to the corresponding ketone. It was during this latter study that we unexpectedly observed small amounts of R-aryl ketone products. For example, GC analysis of the crude reaction mixture of the attempted Pd-catalyzed coupling of 1-bromo-4-tert-butylbenzene with cyclohexanol showed that tert-butylbenzene was the major product along with small amounts of 2-(4-tert-butylphenyl) cyclohexanone (2%), Scheme 1. 8 Realizing the need for a general method for the synthesis of