Kitanosono Taku, Xu Pengyu, Kobayashi Shū
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan), Fax: (+81) 3-5684-0634.
Chem Asian J. 2014 Jan;9(1):179-88. doi: 10.1002/asia.201300997. Epub 2013 Sep 20.
We have developed Cu(II)-catalyzed enantioselective conjugate-addition reactions of boron to α,β-unsaturated carbonyl compounds and α,β,γ,δ-unsaturated carbonyl compounds in water. In contrast to the previously reported Cu(I) catalysis that required organic solvents, chiral Cu(II) catalysis was found to proceed efficiently in water. Three catalyst systems have been exploited: cat. 1: Cu(OH)2 with chiral ligand L1; cat. 2: Cu(OH)2 and acetic acid with ligand L1; and cat. 3: Cu(OAc)2 with ligand L1. Whereas cat. 1 is a heterogeneous system, cat. 2 and cat. 3 are homogeneous systems. We tested 27 α,β-unsaturated carbonyl compounds and an α,β-unsaturated nitrile compound, including acyclic and cyclic α,β-unsaturated ketones, acyclic and cyclic β,β-disubstituted enones, acyclic and cyclic α,β-unsaturated esters (including their β,β-disubstituted forms), and acyclic α,β-unsaturated amides (including their β,β-disubstituted forms). We found that cat. 2 and cat. 3 showed high yields and enantioselectivities for almost all substrates. Notably, no catalysts that can tolerate all of these substrates with high yields and high enantioselectivities have been reported for the conjugate addition of boron. Heterogeneous cat. 1 also gave high yields and enantioselectivities with some substrates and also gave the highest TOF (43,200 h(-1) ) for an asymmetric conjugate-addition reaction of boron. In addition, the catalyst systems were also applicable to the conjugate addition of boron to α,β,γ,δ-unsaturated carbonyl compounds, although such reactions have previously been very limited in the literature, even in organic solvents. 1,4-Addition products were obtained in high yields and enantioselectivities in the reactions of acyclic α,β,γ,δ-unsaturated carbonyl compounds with diboron 2 by using cat. 1, cat. 2, or cat. 3. On the other hand, in the reactions of cyclic α,β,γ,δ-unsaturated carbonyl compounds with compound 2, whereas 1,4-addition products were exclusively obtained by using cat. 2 or cat. 3, 1,6-addition products were exclusively produced by using cat. 1. Similar unique reactivities and selectivities were also shown in the reactions of cyclic trienones. Finally, the reaction mechanisms of these unique conjugate-addition reactions in water were investigated and we propose stereochemical models that are supported by X-ray crystallography and MS (ESI) analysis. Although the role of water has not been completely revealed, water is expected to be effective in the activation of a borylcopper(II) intermediate and a protonation event subsequent to the nucleophilic addition step, thereby leading to overwhelmingly high catalytic turnover.
我们已经开发出了铜（II）催化的硼对α，β-不饱和羰基化合物以及α，β，γ，δ-不饱和羰基化合物的对映选择性共轭加成反应，反应在水中进行。与先前报道的需要有机溶剂的铜（I）催化不同，发现手性铜（II）催化在水中能高效进行。已开发出三种催化剂体系：催化剂1：氢氧化铜与手性配体L1；催化剂2：氢氧化铜和乙酸与配体L1；催化剂3：醋酸铜与配体L1。其中催化剂1是多相体系，催化剂2和催化剂3是均相体系。我们测试了27种α，β-不饱和羰基化合物和一种α，β-不饱和腈化合物，包括开链和环状的α，β-不饱和酮、开链和环状的β，β-二取代烯酮、开链和环状的α，β-不饱和酯（包括其β，β-二取代形式）以及开链α，β-不饱和酰胺（包括其β，β-二取代形式）。我们发现催化剂2和催化剂3对几乎所有底物都显示出高收率和对映选择性。值得注意的是，对于硼的共轭加成反应，尚未报道有能以高收率和高对映选择性耐受所有这些底物的催化剂。多相催化剂1对一些底物也给出了高收率和对映选择性，并且在硼的不对称共轭加成反应中给出了最高的TOF（43,200 h⁻¹）。此外，这些催化剂体系也适用于硼对α，β，γ，δ-不饱和羰基化合物的共轭加成反应，尽管此类反应在文献中此前非常有限，即使在有机溶剂中也是如此。通过使用催化剂1、催化剂2或催化剂3，在无环α，β，γ，δ-不饱和羰基化合物与双联硼2的反应中，1,4-加成产物以高收率和对映选择性得到。另一方面，在环状α，β，γ，δ-不饱和羰基化合物与化合物2的反应中，使用催化剂2或催化剂3时仅得到1,4-加成产物，而使用催化剂1时仅生成1,6-加成产物。环状三烯酮的反应也显示出类似的独特反应性和选择性。最后，研究了这些在水中独特的共轭加成反应的机理，我们提出了由X射线晶体学和质谱（ESI）分析支持的立体化学模型。尽管水的作用尚未完全揭示，但预计水在硼铜（II）中间体的活化以及亲核加成步骤后的质子化过程中是有效的，从而导致极高的催化周转率。
