分會

第十二分會：元素/金屬有機

摘要

硫亞胺是亞砜的氮雜類似物，在有機合成及藥物化學等領域發(fā)揮重要作用。2009年，Hudson等在IV型膠原蛋白中首次發(fā)現了天然生物分子內S=N鍵的存在（Science 2009, 325, 1230）。在此之后，硫亞胺在化學生物學領域備受關注。傳統(tǒng)的硫亞胺合成是通過硫醚的氧化亞胺化得到。由于必需的氧化條件，此策略面臨官能團兼容性不佳等問題，其他方法僅有幾例報道。因此，開發(fā)具有廣泛官能團耐受性的硫亞胺合成策略仍然是一個挑戰(zhàn)。 提出了一種簡潔高效的銅催化次磺酰胺和芳基硼酸Chan-Lam偶聯(lián)S-芳基化合成硫亞胺的新方法（Fig. 1）。該反應僅需廉價易得的銅催化劑，綠色清潔的氧氣為氧化劑，即可有效促進地S(II)次磺酰胺的高化學選擇性生成S(IV)產物。在這個過程中，S(II)化合物被轉化為S(IV)化合物，S?N單鍵轉化為S=N雙鍵。該反應具有優(yōu)異的化學選擇性、廣泛的官能團兼容性，以最高達96%的產率地獲得各種二芳基、烷基芳基、烯基芳基硫亞胺。產物的保護基可脫除，進一步衍生化。 為了探究反應高化學選擇性S-芳基化的機制，與賓夕法尼亞大學Marisa Kozlowski教授合作展開DFT計算研究，分別計算了次磺酰胺S-芳基化與N-芳基化路徑中關鍵步驟的能量分布。結果表明反應的化學選擇性可能源于轉金屬化過程，次磺酰胺的S原子、O原子與銅金屬中心形成五元雙齒鰲合配位是S-芳基化中轉金屬過渡態(tài)能壘更低的關鍵，從而生成熱力學不利的S-芳基化產物。簡單的反應體系能高效地促進次磺酰胺的高化學選擇反應生成S-芳基化產物，而不是在脫質子位點產生的更穩(wěn)定的N-芳基化產物，區(qū)別于傳統(tǒng)的Chan-Lam偶聯(lián)反應。 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.

關鍵詞

次磺酰胺；Chan-Lam 偶聯(lián)；C-S 鍵；硫亞胺

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