Chiral Copper(II)-Catalyzed Enantioselective Boron Conjugate Additions to α,β-Unsaturated Carbonyl Compounds in Water
Chiral Copper(II)-Catalyzed Enantioselective Boron Conjugate Additions to α,β-Unsaturated Carbonyl Compounds in Water
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DOI：
10.1002/anie.201207343
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Kitanosono, Taku
中科院分区：
文献类型：
--
作者：
Kobayashi, Shu;Xu, Pengyu;Kitanosono, Taku
在现代有机化学中，有机反应通常在有机溶剂中进行，尽管与有机溶剂相比，水是安全的、良性的、环境友好的并且便宜，但是使用水作为反应介质是非常罕见的。[1]在水介质中的有机反应中，有两个主要障碍需要克服。首先，许多反应性底物、试剂和催化剂被水分解或失活。其次，大多数有机物质不溶于水。另一方面，我们从最理想的反应--体内酶促反应--在水中进行的观点出发，研究了水中的有机反应，发现了在水介质中独特的反应性和选择性，这在水起关键作用的有机溶剂中是观察不到的。[2]α-手性硼衍生物是一类重要的化合物，它可以通过与亲核试剂的1，2-迁移作用，将手性硼B键转移到手性O、手性N和手性C键上，并保留立体中心。[3]硼与α，β-不饱和羰基及相关化合物的不对称加成反应是合成α-手性硼化合物的有效途径之一。基于CuI催化的共轭硼基化的开创性报道，[4] Yun埃塔尔报道了CuI催化的共轭硼化反应的对映选择性方法。[5]在此之后，几个催化不对称硼化反应使用CuI与手性配体的报道。[6]此外，还报道了其他金属催化的[7]和无金属的[8]对映选择性硼共轭加成到α，β-不饱和羰基和相关化合物。在所有这些情况下，反应都是在有机溶剂中进行的，据我们所知，还没有在水中进行这种共轭加成的报道。[9]在以前的论文中，我们已经表明，在金属氢氧化物如Zn（OH）2，Cu（OH）2，Bi（OH）3等存在下，烯丙基硼酸酯和丙二烯基硼酸酯与醛和酰腙的加成反应在水介质中顺利进行。[10]在这些反应中，未被用作有机合成催化剂的金属氢氧化物被证明是合适的和稳定的催化剂在水介质中，从硼到第二元素的交换过程是至关重要的，以促进反应。基于从这项工作中得到的提示，我们假设从二（频哪醇合）二硼（B2（pin）2）的B原子到第二元素的类似交换过程。本文报道了Cu（OH）_2与手性配体在水溶液中催化硼对各种α，β-不饱和羰基化合物和腈的不对称加成反应。还描述了在水中非常罕见的手性CuII催化。[11首先，我们进行了B2（pin）2与查耳酮在水中在几种有前途的金属氢氧化物存在下的反应，这些金属氢氧化物预期在水中工作良好。发现一些金属氢氧化物与配体良好地工作。例如，当Cu（OH）2与二苄胺（DBA）结合时，以88%的产率获得所需的1，4-加成产物1a（表1，条目1）。Zn（OH）2显示出较差的反应性（条目2）。然后，我们研究了几种手性配体，试图产生对映选择性反应。在水中的不对称催化是非常难以实现的，因为许多手性催化剂在水的存在下迅速分解。[13]我们已经研究了与水相容的刘易斯酸性金属（阳离子），其中涉及Cu II和Zn II。[14]我们还证明了CuII和ZnII与手性2，2 '-联吡啶配体L1 [15]的组合对于对映选择性环化是有效的。
Organic reactions are usually carried out in organic solvents in modern organic chemistry, and it is very rare to use water as the reaction medium despite water being safe, benign, environmentally friendly, and inexpensive compared with organic solvents.[1] In organic reactions in aqueous media, there are two major obstacles to be surmounted. First, many reactive substrates, reagents, and catalysts are decomposed or deactivated by water. Second, most organic substances are insoluble in water. On the other hand, we have investigated organic reactions in water from the standpoint that the most ideal reactions, enzymatic reactions in vivo, are carried out in water, and have found unique reactivity and selectivity in aqueous media, which are not observed in organic solvents where water plays key roles.[2] α-Chiral boron derivatives are an important class of compounds, because the CÀB linkage can be transferred into CÀO, CÀN, and CÀC bonds through 1, 2-migration of intermediary ate complexes with appropriate nucleophiles, with retention of stereogenic centers.[3] Enantioselective boron conjugate addition to α, β-unsaturated carbonyl and related compounds provides one of the most efficient routes to αchiral boron compounds. Based on seminal reports of CuI-catalyzed conjugate borylation,[4] Yun etal. reported an enantioselective method for CuI-catalyzed conjugate borylation.[5] After that, several catalytic asymmetric borylations using CuI with chiral ligands were reported.[6] Furthermore, other metal-catalyzed [7] and metal-free [8] enantioselective boron conjugate additions to α, β-unsaturated carbonyl and related compounds have also been reported. In all of those cases, the reactions were carried out in organic solvents, and to the best of our knowledge, there has been no report of this conjugate addition in water.[9] In previous papers, we have shown that addition reactions of allylboronates and allenylboronates to aldehydes and acylhydrazones proceeded smoothly in the presence of metal hydroxides such as Zn (OH) 2, Cu (OH) 2, Bi (OH) 3, and others in aqueous media.[10] In these reactions, metal hydroxides that had not been used as catalysts in organic synthesis were shown to be suitable and stable catalysts in aqueous media, and that exchange processes from boron to the second elements were crucial to promote the reactions. Based on a hint obtained from this work, we assumed a similar exchange process from the B atom of bis (pinacolato) diboron (B2 (pin) 2) to a second element. Herein, we report enantioselective boron conjugate additions to various α, β-unsaturated carbonyl compounds and nitrile in water catalyzed by Cu (OH) 2 with a chiral ligand. Very rare chiral CuII catalysis in water is also described.[11, 12] First, we conducted the reaction of B2 (pin) 2 with chalcone in water in the presence of several promising metal hydroxides that were expected to work well in water. It was found that some metal hydroxides worked well with ligands. For example, when Cu (OH) 2 was combined with dibenzylamine (DBA), the desired 1, 4-addition product 1a was obtained in 88% yield (Table1, entry1). Zn (OH) 2 showed inferior reactivity (entry2). We then investigated several chiral ligands in an attempt to produce enantioselective reactions. Asymmetric catalysis in water is extremely difficult to achieve because many chiral catalysts decompose rapidly in the presence of water.[13] We have already investigated watercompatible Lewis acidic metals (cations), in which CuII and ZnII are involved.[14] We have also demonstrated that combinations of CuII and ZnII with chiral 2, 2’-bipyridine ligand L1 [15] were effective for enantioselective ring …