Catalytic asymmetric allylation of hydrazono esters in aqueous media by using ZnF2-chiral diamine
Catalytic asymmetric allylation of hydrazono esters in aqueous media by using ZnF2-chiral diamine
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DOI：
10.1002/anie.200351778
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Kobayashi, S
中科院分区：
文献类型：
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作者：
Hamada, T;Manabe, K;Kobayashi, S
已经开发了刘易斯酸催化剂。[1]其中，烯丙基金属试剂对亚氨基化合物的对映选择性加成[2]提供了一种有用的途径来制备光学活性的高烯丙基胺，高烯丙基胺是有机合成中的重要结构单元，因为高烯丙基胺的g，d-双键可以容易地转化为许多不同的官能团。然而，尽管光学活性高烯丙基胺的合成效用，亚氨基化合物的催化不对称烯丙基化的实例是有限的。最近，我们报道了在H2O/THF中，通过使用化学计量量的氟化锌和催化量的手性二胺和TfOH（TfOH=三氟甲磺酸）的组合，酰基亚肼基酯的催化不对称Mannich型反应。[3]酰腙是甚至在水性介质中比亚胺更稳定的亚胺替代物。[4]此外，肼，如曼尼希反应或烯丙基化反应中的产物，是令人感兴趣的化合物，不仅因为肼本身可以用作独特的结构单元，[5]还因为如果NH 4 N键可以断裂，则得到胺。因此，腙的不对称烯丙基化被认为是一种通用的方法，尽管没有催化形式的实例。[6]在此，我们描述了第一个催化不对称烯丙基化酰腙，特别是酰肼酯。在水性介质中使用手性Zn催化剂，反应进行得很顺利。我们将重点放在烯丙基三甲氧基硅烷作为烯丙基化剂[7，8]，因为它可以很容易地形成五配位硅酸盐[9]，并且从毒性的角度来看，与烯丙基锡化合物相比，它是一种优选的试剂。作为手性催化剂体系，我们最初使用ZnF 2 [10]（100摩尔%）、二胺1（10摩尔%）和TfOH（1摩尔%）的组合，其对先前的曼尼希型反应有效。亚肼基酯2与烯丙基三甲氧基硅烷的反应在H2O/THF（1 ∶ 9）中进行，以中等产率得到相应的烯丙基化产物3，具有相对高的ee值（表1，条目1）。有趣的是，发现在曼尼希型反应中必不可少的TfOH在烯丙基化反应中不需要（表1，条目2）。此外，即使当仅使用20摩尔%的ZnF 2时，烯丙基化也以良好的产率进行（表1，条目3），尽管在曼尼希型反应中需要大于50摩尔%的ZnF 2以实现高产率。这些结果表明，催化量的氟阴离子是足够的烯丙基化，而化学计量的氟阴离子是需要在曼尼希型反应。氟阴离子被认为是该反应中的关键，因为Zn（OTf）2没有产生产物（表1，条目5）。此外，发现1显著加速反应[11]（表1，比较条目2和6）。从这些结果中，可以得出结论，本不对称烯丙基化反应的反应机理，包括催化循环可能不同于以前的曼尼希型反应。我们推测该反应以双重活化进行[12，13]，其中Zn 2+作为刘易斯酸活化2，同时氟阴离子作为刘易斯碱攻击烯丙基三甲氧基硅烷的硅原子。换句话说，首先形成氨基化锌和（MeO）3SiF，随后水解酰胺得到烯丙基化产物3
Lewis acid catalysts have been developed.[1] Among them, enantioselective addition of allylmetal reagents to imino compounds [2] provides a useful route to optically active homoallylic amines, which are important building blocks in organic synthesis as the g, d-double bonds of homoallylic amines can be readily converted into many different functional groups. In spite of the synthetic utility of optically active homoallylic amines, however, examples of catalytic asymmetric allylation of imino compounds are limited. Recently, we reported catalytic asymmetric Mannich-type reactions of acylhydrazono esters in H2O/THF by using a combination of a stoichiometric amount of zinc fluoride and a catalytic amount of a chiral diamine and TfOH (TfOH= Trifluoromethanesulfonic acid).[3] Acylhydrazones are imine surrogates more stable than imines even in aqueous media.[4] Furthermore, hydrazines, such as the products in the Mannich reaction or allylation are interesting compounds, not only because hydrazines themselves can be used as unique building blocks,[5] but also because, if the NÀN bond can be cleaved, amines are obtained. Accordingly, asymmetric allylation of hydrazones is considered to be a versatile methodology, although there are no examples of a catalytic version.[6] Herein, we describe the first catalytic asymmetric allylation of acylhydrazones, especially acylhydrazono esters. The reactions proceeded smoothly by using a chiral Zn catalyst in aqueous media.We focused on allyltrimethoxysilane as an allylating agent,[7, 8] because it can form a pentacoordinate silicate easily,[9] and is a preferable reagent compared with allyltin compounds from the standpoint of toxicity. As a chiral catalyst system, we initially used the combination of ZnF2[10](100 mol%), diamine 1 (10 mol%), and TfOH (1 mol%), which was effective for the previous Mannich-type reaction. The reaction of hydrazono ester 2 with allyltrimethoxysilane was conducted in H2O/THF (1: 9), to afford the corresponding allylated product 3 in moderate yield with a relatively high ee value (Table 1, entry 1). Interestingly, it was found that TfOH, which was essential in the Mannich-type reaction, was not needed in the allylation reaction (Table 1, entry 2). Moreover, even when only 20 mol% of ZnF2 was used, the allylation proceeded with a good yield (Table 1, entry 3), although more than 50 mol% of ZnF2 was necessary to achieve high yields in the Mannich-type reaction. These results indicate that a catalytic amount of the fluoride anion is sufficient for the allylation, while a stoichiometric amount of the fluoride anion is needed in the Mannich-type reaction. The fluoride anion is considered to be a key in this reaction, as Zn (OTf) 2 gave no product (Table 1, entry 5). Furthermore, it was found that 1 accelerated the reaction significantly [11](Table 1, compare entries 2 and 6). From these results, it is concluded that the reaction mechanism including the catalytic cycle of the present asymmetric allylation may be different from that of the previous Mannich-type reaction. We speculate that this reaction proceeds with double activation [12, 13] in which Zn2+ acts as a Lewis acid to activate 2 and, at the same time, the fluoride anion acts as a Lewis base to attack the silicon atom of allyltrimethoxysilane. In other words, the zinc amide and (MeO) 3SiF are formed first, and subsequent hydrolysis of the amide affords allylated product 3