Metallaphotoredox-catalysed sp(3)-sp(3) cross-coupling of carboxylic acids with alkyl halides.
Metallaphotoredox-catalysed sp(3)-sp(3) cross-coupling of carboxylic acids with alkyl halides.
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DOI：
10.1038/nature19056
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发表时间：
2016-08-18
期刊：
影响因子：
64.8
通讯作者：
MacMillan DW
中科院分区：
文献类型：
--
作者：
Johnston CP;Smith RT;Allmendinger S;MacMillan DW
在过去的半个世纪里，过渡金属介导的交叉偶联反应改变了复杂有机分子的合成方式。事实上，这些转化的可预测性和化学选择性导致它们在大量化学研究领域中被广泛采用。然而，构建sp3-sp3键，有机化学的基本单元，仍然是交叉偶联反应工程的一个重要而难以捉摸的目标。与使用sp2-杂化物质的相关程序相比，通过过渡金属催化形成sp3-sp3键的方法的开发在历史上受到有害副反应的阻碍，例如Pd催化的β-氢化物消除，以及烷基卤化物不愿进行氧化加成。为了解决这个问题，许多研究小组已经证明了镍催化的交叉偶联过程的可行性，以形成sp3-sp3键，利用有机金属亲核试剂和烷基亲电试剂。特别地，烷基卤化物与预生成的有机锌、格氏试剂和有机硼烷物质的偶联已经用于提供不同的分子结构。然而，差的步骤和原子经济性沿着以及与制造、携带和使用这些敏感耦合伙伴相关的操作困难阻碍了它们的广泛采用。因此，建立一种通用的sp3-sp3偶联技术的前景将是对依赖于有机分子构建的研究领域的有价值的补充，该技术采用工作台稳定的天然有机官能团，而不需要预官能化或底物衍生化。在这里，我们表明，光氧化还原和镍催化的协同合并，使sp3-sp3键的直接形成，仅使用简单的羧酸和烷基卤化物作为亲核和亲电耦合的合作伙伴，分别。所概述的方案适用于广泛的伯羧酸和仲羧酸，并且不需要自由基稳定基团的存在。通过从市售起始材料分四步快速合成药用替罗非班，说明了这种偶联策略的优点。
Over the last half-century, transition metal-mediated cross-coupling reactions have changed the way in which complex organic molecules are synthesized. Indeed, the predictable and chemoselective nature of these transformations has led to their widespread adoption across a vast array of chemical research areas. However, the construction of sp3–sp3 bonds, a fundamental unit of organic chemistry, remains an important yet elusive objective for cross-coupling reaction engineering. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3–sp3 bond formation via transition metal catalysis has been historically hampered by deleterious side-reactions, such as β-hydride elimination with Pd-catalysis, and the reluctance of alkyl halides to undergo oxidative addition. To address this issue, a number of research groups have demonstrated the feasibility of nickel-catalyzed cross-coupling processes to form sp3–sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pregenerated organozinc, Grignard, and organoborane species has been used to furnish diverse molecular structures. However, the poor step and atom economies along with the operational difficulties associated with making, carrying, and using these sensitive coupling partners has hindered their widespread adoption. The prospect of establishing a generically useful sp3–sp3 coupling technology that employs bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be a valuable addition to fields of research that rely on organic molecule construction. Here, we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3–sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. The outlined protocol is suitable for a wide array of primary and secondary carboxylic acids and does not require the presence of radical stabilizing groups. The merit of this coupling strategy is illustrated by the expedient synthesis of the pharmaceutical tirofiban in four steps from commercially available starting materials.
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DOI：
10.1126/science.1255525
发表时间：
2014-07-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zuo Z;Ahneman DT;Chu L;Terrett JA;Doyle AG;MacMillan DW
通讯作者：
MacMillan DW
影响因子：
64.8
作者：
Tasker SZ;Standley EA;Jamison TF
通讯作者：
Jamison TF
影响因子：
12.9
作者：
Haas, Diana;Hammann, Jeffrey M.;Knochel, Paul
通讯作者：
Knochel, Paul
影响因子：
64.8
作者：
Terrett JA;Cuthbertson JD;Shurtleff VW;MacMillan DW
通讯作者：
MacMillan DW
影响因子：
15
作者：
Sahoo, Basudev;Hopkinson, Matthew N.;Glorius, Frank
通讯作者：
Glorius, Frank