Rhodium-catalyzed asymmetric [5+2] cycloaddition of alkyne-vinylcyclopropanes.
Rhodium-catalyzed asymmetric [5+2] cycloaddition of alkyne-vinylcyclopropanes.
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DOI：
10.1002/chem.200901463
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发表时间：
2009-09
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通讯作者：
R. Shintani;H. Nakatsu;K. Takatsu;Tamio Hayashi
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作者：
R. Shintani;H. Nakatsu;K. Takatsu;Tamio Hayashi
过渡金属催化乙烯基环丙烷与碳碳不饱和键的[5+2]环加成是构建七元碳环的有效方法。几种过渡金属如铑、钌、镍和铁可以催化这些以炔烃为反应伙伴的反应，并且烯烃和丙二烯也可以在铑催化下使用。然而不幸的是，这种有用的转化的不对称变体的开发迄今为止尚未取得太大成功。事实上，据我们所知，只有 Wender 最近的一份报告解决了这个问题，使用阳离子 Rh/(R)-binap 催化剂实现了几种烯烃束缚的乙烯基环丙烷的高对映选择性。相比之下，对于炔烃-乙烯基环丙烷的环加成，迄今为止还没有有效的催化不对称方法。在此，我们描述了通过使用与手性亚磷酰胺配体配位的铑配合物来开发这种不对称催化，实现了非常高的对映体过量（高达> 99.5 % ee）。最初，我们使用炔烃-乙烯基环丙烷 1a 作为模型底物，并尝试在 5 mol% 阳离子 Rh/(R)-binap 络合物存在下在二氯甲烷中于 30 8°C 下进行环加成反应（表 1，条目 1）。在这些条件下，5小时后获得了37%的环加合物2a产率，中等ee值为64%。使用其他轴向手性双膦配体，例如 (R)-segphos 和 (R)-H8-binap [13]，在其他相同条件下会导致较低的产率和对映选择性（产率 18–29%，ee 46–55%；条目 2 和 3）。相比之下，手性亚磷酰胺配体 (S,S,S)-3（Rh 的 1.5 当量）诱导了更好的对映选择性（75% ee；条目 4），其非对映异构体配体 (S,R,R)-3 显着提高了反应活性和立体选择性，产物 2a 的产率高达 88%，ee 高达 99%（条目 5）。通过X射线晶体分析确定2a的绝对构型为(R)，如图1所示。使用配体(S,R,R)-3的本发明催化范围如表2所示。不仅芳基(1a-c)而且烷基(1d和1e)都可以很好地耐受作为炔烃上的取代基，导致相应的环加合物2具有一致的高产率和优异的性能。对映选择性（产率 87–90%，94% ee；条目 1–6），配体 (S,R,R)-3 的量可减少至 6 mol%（1.2 当量 Rh），如条目 2 所示。具有末端炔烃的底物 1f 也可实现高对映选择性，尽管 [a] Dr. R. Shintani、H. Nakatsu、K. Takatsu、Prof. T. Hayashi 博士 京都大学科学研究生院化学系，Sakyo，Kyoto 606-8502（日本） 传真：(+81) 75-753-3988 电子邮件：shintani@kuchem.kyoto-u.ac.jp thayashi@kuchem.kyoto-u.ac.jp 本文的支持信息可在 WWW 上找到http://dx.doi.org/10.1002/chem.200901463。表 1. 1 a 的铑催化不对称 [5+2] 环加成反应中的配体效应。
Transition-metal-catalyzed [5+2] cycloaddition of vinylcyclopropanes with carbon carbon unsaturated bonds is an efficient way of constructing seven-membered carbocycles. Several transition metals such as rhodium, ruthenium, nickel, and iron can catalyze these reactions with alkynes as the reaction partner, and alkenes and allenes can also be employed under rhodium catalysis. Unfortunately, however, the development of asymmetric variants of this useful transformation has not met much success so far. In fact, to the best of our knowledge, only a recent report by Wender addressed this issue, achieving high enantioselectivity for several alkene-tethered vinylcyclopropanes using a cationic Rh/(R)-binap catalyst. For cycloaddition of alkyne–vinylcyclopropanes, in contrast, there is no effective catalytic asymmetric method available to date. Herein we describe the development of such an asymmetric catalysis by the use of a rhodium complex coordinated with chiral phosphoramidite ligand, achieving very high enantiomeric excesses (up to >99.5 % ee). Initially, we employed alkyne–vinylcyclopropane 1 a as a model substrate and attempted a cycloaddition reaction in the presence of 5 mol % of a cationic Rh/(R)-binap complex in dichloromethane at 30 8C (Table 1, entry 1). Under these conditions, 37 % yield of cycloadduct 2 a was obtained after 5 h with moderate ee value of 64 %. The use of other axially chiral bisphosphine ligands such as (R)-segphos and (R)-H8-binap [13] resulted in lower yields and enantioselectivity under otherwise the same conditions (18–29 % yield, 46–55 % ee ; entries 2 and 3). In contrast, chiral phosphoramidite ligand (S,S,S)-3 (1.5 equiv to Rh) induced somewhat better enantioselectivity (75 % ee ; entry 4) and its diastereomeric ligand (S,R,R)-3 dramatically improved both reactivity and stereoselectivity, giving product 2 a in 88 % yield with as high as 99 % ee (entry 5). The absolute configuration of 2 a thus obtained was determined to be (R) by X-ray crystallographic analysis as shown in Figure 1. The scope of the present catalysis using ligand (S,R,R)-3 is illustrated in Table 2. Not only aryl groups (1 a–c) but also alkyl groups (1 d and 1 e) are well tolerated as the substituent on the alkyne, leading to the corresponding cycloadducts 2 with uniformly high yield and excellent enantioselectivity (87–90 % yield, 94 % ee ; entries 1–6), and the amount of ligand (S,R,R)-3 can be reduced to 6 mol % (1.2 equiv to Rh) as shown in entry 2. High enantioselectivity is also achieved with substrate 1 f having a terminal alkyne, although [a] Dr. R. Shintani, H. Nakatsu, K. Takatsu, Prof. Dr. T. Hayashi Department of Chemistry, Graduate School of Science Kyoto University, Sakyo, Kyoto 606-8502 (Japan) Fax: (+81) 75-753-3988 E-mail : shintani@kuchem.kyoto-u.ac.jp thayashi@kuchem.kyoto-u.ac.jp Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200901463. Table 1. Ligand effect in the rhodium-catalyzed asymmetric [5+2] cycloaddition of 1 a.