Zinc(II)-Catalyzed Addition of Grignard Reagents to Ketones
Zinc(II)-Catalyzed Addition of Grignard Reagents to Ketones
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DOI：
10.1021/jo100563p
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发表时间：
2010-08-06
影响因子：
3.6
通讯作者：
Ishihara, Kazuaki
中科院分区：
文献类型：
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作者：
Hatano, Manabu;Ito, Orie;Ishihara, Kazuaki
有机金属试剂与羰基化合物的加成反应已成为通过形成碳-碳键合成叔醇和仲醇的一种通用方法。然而，由于有机金属试剂缺乏良好的亲核性或存在强碱性，由酮有效合成叔醇特别困难，因此受到限制。我们最近开发了使用ZnCl 2、Me 3SiCH 2 MgCl和LiCl的格氏试剂（RMgX：R =烷基、芳基; X = Cl、Br、I）的酮的高效催化烷基化和芳基化反应，其有效地使有问题的副反应最小化。原则上，RMgBr和RMgI与羰基化合物加成的反应性低于RMgCl。因此，这种具有均相催化ZnCl 2中心点Me 3SiCH 2 MgCl中心点LiCl的新方法是相当有吸引力的，因为RMgBr和RMgI，其容易制备和/或市售，如RMgCl，可以成功地应用。醛亚胺与酮、醛一样，都能有效地应用于该催化反应，并以较高的产率得到相应的仲胺。在β-硅基效应和盐效应方面，原位合成的[R（Me_3SiCH_2）（2）Zn]（-）[Li]（+）[MgX_2]（m）[LiCl]（n）（X = Cl/Br/I）可能是促进反应的关键催化剂。这种可靠的ZnCl_2中心点Me_3SiCH_2 MgCl中心点LiCl体系在格氏试剂加成羰基化合物中的简单性可能对工业以及学术应用有吸引力。
The addition of organometallic reagents to carbonyl compounds has become a versatile method for synthesizing tertiary and secondary alcohols via carbon-carbon bond formation. However, due to the lack of good nucleophilicity or the presence of strong basicity of organometallic reagents, the efficient synthesis of tertiary alcohols from ketones has been particularly difficult and, thus, limited. We recently developed highly efficient catalytic alkylation and arylation reactions to ketones with Grignard reagents (RMgX: R = alkyl, aryl; X = Cl, Br, I) using ZnCl2, Me3SiCH2MgCl, and LiCl, which effectively minimize problematic side reactions. In principle, RMgBr and RMgI are less reactive than RMgCl for the addition to carbonyl compounds. Therefore, this novel method with homogeneous catalytic ZnCl2 center dot Me3SiCH2MgCl center dot LiCl is quite attractive, since RMgBr and RMgI, which are easily prepared and/or commercially available, like RMgCl, can be applied successfully. As well as ketones and aldehydes, aldimines were effectively applied to this catalysis, and the corresponding secondary amines were obtained in high yield. With regard to mechanistic details concerning beta-silyl effect and salt effect, in situ-prepared [R(Me3SiCH2)(2)Zn](-)[Li](+)[MgX2](m)[LiCl](n) (X = Cl/Br/I) is speculated to be a key catalytic reagent to promote the reaction effectively. The simplicity of this reliable ZnCl2 center dot Me3SiCH2MgCl center dot LiCl system in the addition of Grignard reagents to carbonyl compounds might be attractive for industrial as well as academic applications.