Ruthenium-catalyzed enantioselective propargylation of aromatic compounds with propargylic alcohols via allenylidene intermediates.
Ruthenium-catalyzed enantioselective propargylation of aromatic compounds with propargylic alcohols via allenylidene intermediates.
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DOI：
10.1002/anie.200701261
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发表时间：
2007-08
影响因子：
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通讯作者：
H. Matsuzawa;Y. Miyake;Y. Nishibayashi
中科院分区：
文献类型：
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作者：
H. Matsuzawa;Y. Miyake;Y. Nishibayashi
弗里德尔-克来福特反应是有机合成中最可靠、最强大的 CÀC 键形成工具之一。[1]近年来，芳香族化合物的不对称弗里德尔-克来福特烷基化反应的发展受到了广泛关注。该反应在芳香族化合物的苄基位置引入手性中心，[2]并且可以使用多种路易斯酸和有机催化剂来促进该反应。[2, 3]然而，不对称弗里德尔-克来福特烷基化的成功例子仍然局限于与环氧化物、羰基化合物、活化烯烃及其类似物等三种类型的亲电子试剂的反应。[2, 3]我们最近公开了该反应的新颖催化活性[4]硫属醇盐桥联二钌络合物 [6]，例如 [{Cp* RuCl (m2-YR)} 2](Cp*= h5-C5Me5; Y= S, Se, Te; R= Me, nPr, iPr) 和 [Cp* RuCl (m2-YR) 2RuCp*(OH2)] OTf (Tf= 三氟甲磺酰基)，可用于多种有机转化钌-亚烯基中间体。[6]其中一个转化是芳香族化合物与炔丙醇的炔丙基化。[7-9]考虑到我们之前开发的钌催化的炔丙醇与丙酮的对映选择性炔丙基取代反应（高达82% ee）。[10]我们在此报告了使用炔丙醇作为亲电子试剂进行不对称弗里德尔-克来福特烷基化的成功示例。在催化量的手性硫醇盐桥连二钌络合物 2a（由四核钌 (II) 络合物 [Cp* RuCl] 4 和手性二硫化物 [10b] 在 THF 中原位制备）的存在下，在 ClCH2CH2Cl 中于室温下用 2-甲基呋喃（10 当量）处理 1-苯基-2-丙炔-1-醇 (1a) 12 小时），NH4BF4 在 608℃ 3 小时，得到 2-甲基-5-（1-苯基-2-丙炔基）呋喃（3a），分离得到的收率为 75%，ee 为 77%（表 1，条目 1）。在稍高的温度（例如 808C）下观察到 3a 的产率下降（表 1，条目 2）。在所有情况下，特别是当反应在高温下进行时，都观察到相应低聚物的形成作为副产物。另一方面，反应在较低温度（例如408℃和室温）下进行，但3a的产率略有下降（表1，条目3和4）。即使不使用过量的 2-甲基呋喃，反应也会继续进行，但 3a 的产率会下降（表 1，条目 5 和 6）。在所有情况下，对映选择性都没有受到很大影响。研究了各种光学活性二硫化物作为1a与2-甲基呋喃反应中的手性配体，如方案1所示。手性二硫化物苯环的2-、3-和5-位上存在三个芳基对于实现高对映选择性是必要的。事实上，使用苯环上带有一个或两个苯基的手性二硫化物（2b-2f）明显降低了对映选择性。在丙酮与炔丙醇的催化炔丙基化反应中也观察到了类似的趋势。[10b]
The Friedel–Crafts reaction is one of the most reliable and powerful CÀC bond forming tools in organic synthesis.[1] Recently, the development of an asymmetric Friedel–Crafts alkylation of aromatic compounds has received a great deal of attention. This reaction introduces chiral centers at the benzylic position of aromatic compounds,[2] and a variety of Lewis acids and organocatalysts are available to promote the reaction.[2, 3] However, the successful examples of asymmetric Friedel–Crafts alkylation are still limited to reactions with three types of electrophiles such as epoxides, carbonyl compounds, activated alkenes, and their analogues.[2, 3] We have recently disclosed the novel catalytic activity [4] of chalcogenolate-bridged diruthenium complexes [5] such as [{Cp* RuCl (m2-YR)} 2](Cp*= h5-C5Me5; Y= S, Se, Te; R= Me, nPr, iPr) and [Cp* RuCl (m2-YR) 2RuCp*(OH2)] OTf (Tf= trifluoromethanesulfonyl) for many organic transformations via ruthenium–allenylidene intermediates.[6] One of these transformations is the propargylation of aromatic compounds with propargylic alcohols.[7–9] We envisaged the development of a catalytic enantioselective propargylation of aromatic compounds as a new type of asymmetric Friedel–Crafts alkylation of aromatic compounds by taking account of our previous development of the ruthenium-catalyzed enantioselective propargylic substitution reactions of propargylic alcohols with acetone (up to 82% ee).[10] We report here a successful example of an asymmetric Friedel–Crafts alkylation by using propargylic alcohols as electrophiles. Treatment of 1-phenyl-2-propyn-1-ol (1a) with 2-methylfuran (10 equiv) in ClCH2CH2Cl in the presence of a catalytic amount of a chiral thiolate-bridged diruthenium complex 2a,(prepared in situ from the tetranuclear ruthenium (II) complex [Cp* RuCl] 4 and a chiral disulfide [10b] in THF at room temperature for 12 h), and NH4BF4 at 608C for 3 h afforded 2-methyl-5-(1-phenyl-2-propynyl) furan (3a), which was isolated in 75% yield with 77% ee (Table 1, entry 1). A decrease in yield of 3a was observed at slightly higher temperatures, such as 808C (Table1, entry2). The formation of the corresponding oligomers was observed as side products in all cases, especially when the reaction was carried out at high temperature. On the other hand, the reaction at lower temperatures, such as 408C and at room temperature, proceeded similarly with a slight decrease in the yield of 3a (Table 1, entries 3 and 4). Even without the use of excess 2-methylfuran, the reaction proceeded, but the yield of 3a decreased (Table1, entries5 and 6). In all cases, the enantioselectivity was not greatly affected. A variety of optically active disulfides were investigated as chiral ligands in the reaction of 1a with 2-methylfuran as shown in Scheme 1. The presence of three aryl groups in the 2-, 3-, and 5-positions of the benzene ring of the chiral disulfide was necessary to achieve the high enantioselectivity. In fact, the use of chiral disulfides (2b–2 f) with one or two phenyl groups on the benzene ring apparently decreased the enantioselectivity. A similar tendency has been observed in the catalytic propargylation of acetone with propargylic alcohols.[10b]