Palladium-catalyzed hydroamination of 1,3-dienes:: A colorimetric assay and enantioselective additions
Palladium-catalyzed hydroamination of 1,3-dienes:: A colorimetric assay and enantioselective additions
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DOI：
10.1021/ja005881o
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发表时间：
2001-05-09
影响因子：
15
通讯作者：
Hartwig, JF
中科院分区：
文献类型：
--
作者：
Löber, O;Kawatsura, M;Hartwig, JF
轻微的，选择性的胺与二烯形成烯丙胺的1:1反应是罕见的，并且仅限于镍催化的环二烷基胺反应。2 .晚期过渡金属催化、胺诱导的丁二烯端粒化和亲核试剂对二烯的氧化1,4加成现在已经为人所知，钯催化的胺对活性更强的烯和烯的加成也有报道。然而，二烯与胺的反应通常发生在高温下，并产生同分异构体混合物。1c, f， g我们报道了在室温下使用高通量比色法来鉴定区域选择性1:1二烯氢胺化的催化剂。6,7二烯氢胺化的范围很广，包括对映选择性的例子。为了同时评估大量潜在的氢胺化催化剂，我们开发了一种比色法来监测苯胺的存在或不存在。在酸的存在下，糠醛与2等量的苯胺发生缩合开环，而不是与烯丙基胺产物发生缩合开环，从而生成红色产物。因此，在芳香胺的催化反应中加入糠醛和酸将揭示哪些催化剂最活跃；消耗大量苯胺的反应将显示没有红色。通常，反应被稀释以区分颜色。图1显示了苯胺与环己二烯反应的比色测定结果。在加入反应物之前，在96孔玻璃板上组装了一组由市售配位配合物和常见膦生成的潜在催化剂。酸已被证明能抑制丁二烯、烯和烯的端粒化。因此，我们在存在和不存在10mol % TFA的情况下进行了反应。在有酸的情况下，一些反应在4小时后，通过比色法，苯胺完全转化，而在没有酸的情况下，反应需要更长的时间来观察反应。气相色谱/质谱分析显示苯胺的转化表明在没有端粒化的情况下形成1:1加合物。这些实验表明，由[Pd （π-烯丙基）Cl] 2和PPh3形成的配合物活性最高（图1）。已知这两种材料会形成PPh3连接的Pd(0), 9，并且在THF中的NMR实验表明，混合后立即形成Pd (PPh3) 4。因此，我们使用现成的Pd (PPh3) 4进行制备规模的反应。表1显示了用2mol % Pd (PPh3) 4和10mol % TFA作为催化剂和助催化剂的制备反应的结果。反应通常在室温下在甲苯中运行24小时，但可以使用更短的时间。无论苯胺上是否存在吸电子、给电子或邻位取代基，所有反应均以高收率进行。富电子苯胺（第7,9项）和贫电子苯胺（第5,6项）都能高产出加成产物，尽管反应(1)(a)关于端粒化的综述，参见：Behr， a . Aspects of Homogeneous Catalysis；Kluwer：多德雷赫特，荷兰，1984；第五卷，第3-73页。(b)高桥，s；Shibano t;Hagihara， N.牛。化学。Soc。[j] . 1968, 41(1): 454-460。(c)高桥，k；宅一生,a;哈塔，G.布尔。化学。Soc。中华医学杂志，1992,15(4):1183-1191。(d) Patel，文学士；迪克森,我;见鬼，r.f.j.org。化学，1978,43,5018-5020。(e)贝格，J.；Meier， F. J. Prakt。化学，1980,322,69-80。(f)阿姆布鲁斯特，卢旺达；摩根,MM;施密特,杰;刘,CM;莱利,RM;Zabrowski DL;刘志强，刘志强。有机金属学报，1998,5(5):344 - 344。(g)彼得鲁什基纳，EA；扎哈尔金，李泽夫。Akad。研究爵士。金。1992,8,1794…
Mild, selective 1: 1 reactions of amines with dienes to form allylic amines are rare1 and limited to the reaction of cyclic dialkylamines catalyzed by nickel. 2 Late transition metalcatalyzed, amine-induced telomerizations of butadiene1 and oxidative 1, 4 addition of nucleophiles to dienes3 are now well known, and the palladium-catalyzed additions of amines to more reactive eneynes4 and allenes5 have been reported. However, reactions of dienes with amines generally occur at high temperatures and produce isomeric mixtures. 1c, f, g We report the use of a high-throughput colorimetric assay to identify catalysts for the regioselective 1: 1 hydroamination of dienes at room temperature. 6, 7 The scope of the diene hydroamination is broad and includes enantioselective examples. To evaluate simultaneously a large number of potential catalysts for the hydroamination, we developed a colorimetric method to monitor the presence or absence of anilines. Furfural undergoes a condensation and ring opening with 2 equiv of aniline, but not with the allylic amine product, in the presence of acid to create a red product. 8 Thus, addition of furfural and acid to catalytic reactions of aromatic amines will reveal which catalysts are most active; reactions that consume the largest amount of aniline will show an absence of the red color. Typically, the reactions were diluted to distinguish the colors. Figure 1 displays the results of this colorimetric assay for the reaction of aniline with cyclohexadiene. A set of potential catalysts generated from commercially available coordination complexes and common phosphines was assembled from stock solutions in a 96-well glass plate prior to the addition of reactants. Acids have been shown to inhibit telomerization of butadiene, eneynes, and allenes. Thus, we conducted reactions in the presence and absence of 10 mol% of TFA. After 4 h, some reactions conducted in the presence of acid showed, by the colorimetric assay, complete conversion of aniline, while reactions in the absence of acid required longer times to observe reaction. GC/MS analysis of solutions showing conversion of aniline indicated formation of1: 1 adducts without telomerization. These experiments showed that complexes formed from [Pd (π-allyl) Cl] 2 and PPh3 were the most active (Figure 1). These two materials are known to form PPh3-ligated Pd (0), 9 and NMR experiments in THF showed formation of Pd (PPh3) 4 immediately upon mixing. Thus, we used the readily available Pd (PPh3) 4 for preparative-scale reactions. Table 1 shows results from preparative reactions containing 2 mol% Pd (PPh3) 4 and 10 mol% TFA as catalyst and cocatalyst. Reactions were typically run at room temperature in toluene for 24 h, but shorter times could be used. All reactions occurred in high yield regardless of the presence of an electron-withdrawing, electron-donating, or ortho substituent on the aniline. Both the electron-rich (entries 7, 9) and electron-poor anilines (entries 5, 6) gave the addition products in high yields, although reactions (1)(a) For a review on telomerizations, see: Behr, A. Aspects of Homogeneous Catalysis; Kluwer: Dordrecht, The Netherlands, 1984; Vol. 5, pp 3-73.(b) Takahashi, S.; Shibano, T.; Hagihara, N. Bull. Chem. Soc. Jpn. 1968, 41, 454-460.(c) Takahashi, K.; Miyake, A.; Hata, G. Bull. Chem. Soc. Jpn. 1972, 45, 1183-1191.(d) Patel, BA; Dickerson, JE; Heck, R. F. J. Org. Chem. 1978, 43, 5018-5020.(e) Beger, J.; Meier, F. J. Prakt. Chem. 1980, 322, 69-80.(f) Armbruster, RW; Morgan, MM; Schmidt, JL; Lau, CM; Riley, RM; Zabrowski, DL; Dieck, HA Organometallics 1986, 5, 234-237.(g) Petrushkina, EA; Zakharkin, LI IzV. Akad. Nauk Ser. Khim. 1992, 8, 1794 …