Transition-Metal-Free Suzuki-Type Cross-Coupling Reaction of Benzyl Halides and Boronic Acids via 1,2-Metalate Shift
Transition-Metal-Free Suzuki-Type Cross-Coupling Reaction of Benzyl Halides and Boronic Acids via 1,2-Metalate Shift
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卤化苄和硼酸通过 1,2- 金属酸位移进行的无过渡金属 Suzuki 型交叉偶联反应
DOI：
10.1021/jacs.8b00380
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发表时间：
2018-02-21
影响因子：
15
通讯作者：
Huang, Yong
中科院分区：
文献类型：
--
作者：
He, Zhiqi;Song, Feifei;Huang, Yong
有机硼化合物与亲电体的交叉偶联(Suzuki-Miyaura反应)极大地促进了C-C键的形成，在药物化学中得到了广泛的应用。在过去的50年里，过渡金属在这一重要转变的催化循环中发挥了核心作用。在这个过程中，多个碳-卤键之间的化学选择性是一个共同的挑战。特别是，由于不利的过渡态和键强度，过渡金属与烷基卤化物而不是芳基卤化物的选择性氧化加成是困难的。我们描述了一种新的方法，它使用单一的有机硫化物催化剂，通过两性离子硼“ATE”中间体来激活C(sp(3))卤化物和芳基硼酸。这种“ATE”物种经历了1，2-金属酸的转变，以提供使用氯化苄基和芳基硼酸的铃木偶联产品。可以制备各种二芳基甲烷类似物，包括那些具有复杂和生物活性基元的类似物。反应在无过渡金属的条件下进行，C(sp(2))卤化物，包括芳基溴化物和碘化物不受影响。在使用多卤化底物的高度功能化的二芳基甲烷支架的简化合成中，证明了正交化学选择性。初步的机理实验表明，硫酸盐和硫叶立德都参与了反应，硫盐的形成是整个催化循环中最慢的步骤。
Cross-coupling of organoboron compounds with electrophiles (Suzuki-Miyaura reaction) has greatly advanced C-C bond formation and has been well received in medicinal chemistry. During the past 50 years, transition metals have played a central role throughout the catalytic cycle of this important transformation. In this process, chemoselectivity among multiple carbon-halogen bonds is a common challenge. In particular, selective oxidative addition of transition metals to alkyl halides rather than aryl halides is difficult due to unfavorable transition states and bond strengths. We describe a new approach that uses a single organic sulfide catalyst to activate both C(sp(3)) halides and arylboronic acids via a zwitterionic boron "ate" intermediate. This "ate" species undergoes a 1,2-metalate shift to afford Suzuki coupling products using benzyl chlorides and arylboronic acids. Various diaryl methane analogues can be prepared, including those with complex and biologically active motifs. The reactions proceed under transition-metal-free conditions, and C(sp(2)) halides, including aryl bromides and iodides, are unaffected. The orthogonal chemoselectivity is demonstrated in the streamlined synthesis of highly functionalized diaryl methane scaffolds using multi-halogenated substrates. Preliminary mechanistic experiments suggest both the sulfonium salt and the sulfur ylide are involved in the reaction, with the formation of sulfonium salt being the slowest step in the overall catalytic cycle.