分会

第十二分会：元素/金属有机

摘要

硫亚胺是亚砜的氮杂类似物，在有机合成及药物化学等领域发挥重要作用。2009年，Hudson等在IV型胶原蛋白中首次发现了天然生物分子内S=N键的存在（Science 2009, 325, 1230）。在此之后，硫亚胺在化学生物学领域备受关注。传统的硫亚胺合成是通过硫醚的氧化亚胺化得到。由于必需的氧化条件，此策略面临官能团兼容性不佳等问题，其他方法仅有几例报道。因此，开发具有广泛官能团耐受性的硫亚胺合成策略仍然是一个挑战。 提出了一种简洁高效的铜催化次磺酰胺和芳基硼酸Chan-Lam偶联S-芳基化合成硫亚胺的新方法（Fig. 1）。该反应仅需廉价易得的铜催化剂，绿色清洁的氧气为氧化剂，即可有效促进地S(II)次磺酰胺的高化学选择性生成S(IV)产物。在这个过程中，S(II)化合物被转化为S(IV)化合物，S−N单键转化为S=N双键。该反应具有优异的化学选择性、广泛的官能团兼容性，以最高达96%的产率地获得各种二芳基、烷基芳基、烯基芳基硫亚胺。产物的保护基可脱除，进一步衍生化。 为了探究反应高化学选择性S-芳基化的机制，与宾夕法尼亚大学Marisa Kozlowski教授合作展开DFT计算研究，分别计算了次磺酰胺S-芳基化与N-芳基化路径中关键步骤的能量分布。结果表明反应的化学选择性可能源于转金属化过程，次磺酰胺的S原子、O原子与铜金属中心形成五元双齿鳌合配位是S-芳基化中转金属过渡态能垒更低的关键，从而生成热力学不利的S-芳基化产物。简单的反应体系能高效地促进次磺酰胺的高化学选择反应生成S-芳基化产物，而不是在脱质子位点产生的更稳定的N-芳基化产物，区别于传统的Chan-Lam偶联反应。 Sulfilimines, the aza-analogues of sulfoxides, which play an important role in organic synthesis and pharmaceutical chemistry. Conventionally, sulfilimines are prepared from the sulfides via an oxidative imination strategy, which suffers from limited compatibility with functional groups due to the requisite oxidation conditions. Only several examples of other synthesis methods have been reported. Therefore, the development of mild and efficient synthetic methods to offer sulfilimines with broad functional group tolerance remains a challenge. A simple and efficient copper-catalyzed Chan-Lam S-arylation of sulfenamides for the synthesis of sulfilimines was introduced. The reaction only requires cheap Cu(TFA)2H2O as catalyst, and atmospheric oxygen as oxidant to realize S-arylation of N-benzoylsulfenamides with high chemoselectivity. In this process, S(II) compounds are converted to S(IV) compounds, and S−N single bonds are converted to S=N double bonds. 51 examples of sulfilimines were obtained with a yield of up to 96%, including S,S-diaryl, S-alkyl-S-aryl, and S-aryl-S-alkenyl sulfilimines. The benzoyl-protecting groups could be conveniently removed from sulfilimines, which could be readily transformed into several S(IV) and S(VI) derivatives. In order to explore the mechanism for the highly chemoselective S-arylation of sulfenamides, we cooperated with professor Marisa C. Kozlowski and Lucille A. Wells from University of Pennsylvania. The energy profile of key steps in the S-arylation and N-arylation paths of sulfenamides were calculated respectively. Theoretical calculations show that the chemoselectivity may orginate from the transmetallation process, and the formation of a bidentate chelation between the S atom and O atom of sulfenamide to copper centre is the key to the lower energy barrier of the S-arylation pathway. Examination of the pathway also reveals that the N-arylation product is substantially lower in energy than S-arylation. As such, the formation of the S-arylation product as seen in the current method must arise from kinetic control. A simple reaction system can efficiently promote S-arylation of sulfinamides to produce sulfilimines, rather than more stable N-arylation products at the deprotonation site, which is different from the traditional Chan-Lam coupling reaction.

关键词

次磺酰胺；Chan-Lam 偶联；C-S 键；硫亚胺

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