The first gold-catalyzed C-S bond formation:: Cycloisomerization of α-thioallenes to 2,5-dihydrothiophenes
The first gold-catalyzed C-S bond formation:: Cycloisomerization of α-thioallenes to 2,5-dihydrothiophenes
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DOI：
10.1002/anie.200503846
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Krause, N
中科院分区：
文献类型：
--
作者：
Morita, N;Krause, N
近年来，金催化剂在有机合成中的应用受到了广泛的关注，因为它们在分子间和分子内加成反应、环化反应、环异构化反应和重排反应中表现出了优异的反应活性和选择性。[1]迄今为止，这些金催化的反应已被用于高效地形成C13 C、C13 O和C13 N键。相比之下，似乎没有在金催化剂存在下形成碳-硫键的先例。其基本原理可能是已知有机硫化合物如硫醇、硫化物和二硫化物与过渡金属，特别是与金强烈配位，这使得在这些官能团存在下使用金催化剂不是非常有希望的。金和硫的这种高亲和力经常应用于各种领域，例如在自组装单分子层（SAM）的产生[2]和硫醇金作为药物的用途，例如用于治疗类风湿性关节炎。[3]最近，我们报道了高效的金催化的α-羟基联烯环化异构化为2，5-二氢呋喃[4]，以及α-氨基联烯环化异构化为3-吡咯啉[5]，产率从好到高，具有完全的轴到中心手性转移（即，手性从联烯手性轴转移到新形成的立体中心;方案1）。所形成的杂环产物对于天然产物和药物的合成是非常有用的。相应的，前所未有的，α-硫代联烯环异构化为2，5-二氢噻吩也将是非常有益的。例如，所得杂环的氧化或还原顺利地得到噻吩或四氢噻吩，它们是天然产物和生物活性化合物中的重要结构基序（示意图2）。这些包括抗高血压化合物，[6]潜在的HIV抑制剂，[7]葡萄糖苷酶抑制剂（salacinol，kotalanol），[8]必需辅酶（生物素）[9]和胆囊收缩素B型受体拮抗剂（tetronothiodin）。[10]此外，2，5-二取代四氢噻吩还可以作为手性配体用于对映选择性反应。[11]尽管这些杂环化合物很重要，但2，5-二取代二氢噻吩和四氢噻吩的立体控制合成却很少受到关注。[12]本文报道了通过α-硫代联烯的立体选择性环异构化高效合成2，5-二氢噻吩的方法，这是金催化碳硫键形成的第一个例子。我们用α-硫代丙二烯1a [13]开始我们的研究，该α-硫代丙二烯1a在氩气下在室温下在CH 2Cl 2中用各种硬币金属预催化剂（Au、Ag、Cu; 5-20摩尔%）处理（表1）。
The use of gold catalysts in organic synthesis has received much attention in recent years because they exhibit extraordinary reactivities and selectivities in various transformations such as inter-and intramolecular addition reactions, cyclizations, cycloisomerizations, and rearrangements.[1] To date, these gold-catalyzed reactions have been utilized for the highly efficient formation of CÀC, CÀO, and CÀN bonds. In contrast, there seems to be no precedent for the formation of a carbon–sulfur bond in the presence of a gold catalyst. A rationale for this might be that organosulfur compounds such as thiols, sulfides, and disulfides are known to strongly coordinate to transition metals, especially to gold, which does not render the use of gold catalysts in the presence of these functional groups very promising. This high affinity of gold and sulfur is frequently applied in various fields, for instance in the generation of self-assembled monolayers (SAMs)[2] and the use of gold thiolates as drugs, for example, for the treatment of rheumatoid arthritis.[3] Recently, we reported the highly efficient gold-catalyzed cycloisomerization of α-hydroxyallenes to 2, 5-dihydrofurans,[4] as well as of α-aminoallenes to 3-pyrrolines [5] in good to high yields with complete axis-to-center chirality transfer (that is, chirality transfer from the allenic chirality axis to the newly formed stereogenic center; Scheme 1). The heterocyclic products formed are highly useful for the synthesis of natural products and pharmaceuticals. The corresponding, as yet unprecedented, cycloisomerization of α-thioallenes to 2, 5-dihydrothiophenes would be highly rewarding as well. For example, oxidation or reduction of the resulting heterocycles smoothly affords thiophenes or tetrahydrothiophenes which are important structural motifs in natural products and biologically active compounds (Scheme2). These include antihypertensive compounds,[6] potential inhibitors of HIV,[7] glucosidase inhibitors (salacinol, kotalanol),[8] an essential coenzyme (biotin)[9] and a cholecystokinin type-B receptor antagonist (tetronothiodin).[10] Moreover, 2, 5-disubstituted tetrahydrothiophenes can be utilized as chiral ligands in enantioselective reactions.[11]In spite of the importance of these heterocyclic compounds, the stereocontrolled synthesis of 2, 5-disubstituted dihydrothiophenes and tetrahydrothiophenes has received only scant attention.[12] Herein we report the highly efficient synthesis of 2, 5-dihydrothiophenes by stereoselective cycloisomerization of α-thioallenes, which is the first example of a gold-catalyzed carbon–sulfur bond formation. We initiated our study with the α-thioallene 1a [13] which was treated with various coin-metal precatalysts (Au, Ag, Cu; 5–20 mol%) in CH2Cl2 under argon at room temperature (Table 1).