Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
Department of Chemistry and Biochemistry, Swarthmore College , Swarthmore, Pennsylvania 19081, United States.
J Am Chem Soc. 2017 Apr 26;139(16):5998-6007. doi: 10.1021/jacs.7b02388. Epub 2017 Apr 12.
We report the first reductive coupling of unactivated alkenes with N-methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts under hydrogen atom transfer (HAT) conditions, and an expanded scope for the coupling of alkenes with N-methoxy pyridinium salts. N-Methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts are accessible in 1-2 steps from the commercial arenes or arene N-oxides (25-99%). N-Methoxy imidazolium salts are accessible in three steps from commercial amines (50-85%). In total 36 discrete methoxyheteroarenium salts bearing electron-donating, electron-withdrawing, alkyl, aryl, halogen, and haloalkyl substituents were prepared (several in multigram quantities) and coupled with 38 different alkenes. The transformations proceed under neutral conditions at ambient temperature, provide monoalkylation products exclusively, and form a single alkene addition regioisomer. Preparatively useful and complementary site selectivities in the addition of secondary and tertiary radicals to pyidinium salts are documented: harder secondary radicals favor C-2 addition (2->10:1), while softer tertiary radicals favor bond formation to C-4 (4.7->29:1). A diene possessing a 1,2-disubstituted and 2,2-disubstituted alkene undergoes hydropyridylation at the latter exclusively (61%) suggesting useful site selectivities can be obtained in polyene substrates. The methoxypyridinium salts can also be employed in dehydrogenative arylation, borono-Minisci, and tandem arylation processes. Mechanistic studies support the involvement of a radical process.
我们首次报道了在氢原子转移（HAT）条件下，未活化的烯烃与 N-甲氧基哒嗪鎓、咪唑鎓、喹啉鎓和异喹啉鎓盐的还原偶联反应，并扩展了 N-甲氧基吡啶鎓盐与烯烃偶联的范围。N-甲氧基哒嗪鎓、咪唑鎓、喹啉鎓和异喹啉鎓盐可通过商业芳烃或芳烃 N-氧化物（25-99%）一步或两步制得。N-甲氧基咪唑鎓盐可通过商业胺（50-85%）三步制得。总共制备了 36 种带有供电子、吸电子、烷基、芳基、卤素和卤代烷基取代基的离散的甲氧基杂芳鎓盐（其中几种以多克量制备），并与 38 种不同的烯烃进行了偶联。这些转化在中性条件下、室温下进行，仅生成单烷基化产物，并形成单一的烯烃加成区域异构体。记录了吡啶鎓盐中仲和叔自由基加成的有用且互补的选择性：更硬的仲自由基有利于 C-2 加成（2->10:1），而更软的叔自由基有利于 C-4 键形成（4.7->29:1）。一种具有 1,2-二取代和 2,2-二取代烯烃的二烯仅在后者处进行氢化吡啶化（61%），这表明在多烯底物中可以获得有用的选择性。甲氧基吡啶鎓盐还可用于脱氢芳基化、硼代-Minisci 和串联芳基化过程。机理研究支持自由基过程的参与。
