Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Green Chemistry Center, Peking University, Beijing 100871, China.
Acc Chem Res. 2010 Dec 21;43(12):1486-95. doi: 10.1021/ar100082d. Epub 2010 Sep 17.
Since their development in the 1970s, cross-coupling reactions catalyzed by transition metals have become one of the most important tools for constructing both carbon-carbon and carbon-heteroatom bonds. Traditionally, organohalides were widely studied and broadly used as the electrophile, both in the laboratory and in industry. Unfortunately, the high cost, environmental toxicity, and sluggish preparation often associated with aryl halides can make them undesirable for the large-scale syntheses of industrial applications. However, with the further development of catalytic systems, and particularly of the ligands contained therein, a variety of electrophiles have now been successfully applied to cross-coupling reactions. Oxygen-based electrophiles have attracted much attention due to their ready availability from phenol and carbonyl compounds. Initially, aryl and alkenyl triflates were used in cross-coupling reactions due to their high reactivity; however, low moisture stability and high cost hampered their application. Later, with the development of highly efficient catalytic systems, the less reactive sulfonates and phosphates were successfully employed in cross-coupling reactions. Although they have higher stability and can be easily prepared, low atom economy remains an obstacle to their broader utility. Our group has worked to directly apply the abundant and readily available oxygen-containing compounds, such as phenols, alcohols, ethers, and carbonyl compounds, to cross-coupling reactions. In this Account, we describe our recent efforts in transition-metal-catalyzed cross-coupling reactions of new O-based electrophiles via C-O bond activation. We began by developing the methylation of aryl methyl ethers and benzyl methyl ethers via Ni-catalyzed selective C-O bond cleavage. With the refined Ni-based catalytic system, we further applied aryl/alkenyl carboxylates and carbamates to Suzuki-Miyaura, Negishi, and Kumada-Tamao-Corriu reactions to construct various biaryl scaffolds and highly substituted alkenes. To further improve the carbon atom economy, we developed the diaryl sulfates as one-by-one electrophiles (that is, both aryl groups are used in the reaction). Most recently, we have achieved the first successful cross-coupling reaction of magnesium naphtholates with aryl Grignard reagents. These results extend aryl and benzyl ethers, aryl and alkenyl carboxylates/carbamates, and magnesium naphtholates as novel electrophiles in cross-coupling reactions. More importantly, these studies contribute to our better understanding the intrinsic nature of C-O bonds, which were traditionally considered "inert" but clearly show enormous synthetic potential with the proper catalysts.
自 20 世纪 70 年代发展以来，过渡金属催化的交叉偶联反应已成为构建碳-碳和碳-杂原子键的最重要工具之一。传统上，有机卤化物被广泛研究并广泛用作亲电试剂，无论是在实验室还是在工业中。不幸的是，芳基卤化物通常与高成本、环境毒性和缓慢的制备相关联，这使得它们不适合大规模合成工业应用。然而，随着催化体系的进一步发展，特别是其中的配体，各种亲电试剂现已成功应用于交叉偶联反应。基于氧的亲电试剂由于可从苯酚和羰基化合物中获得而受到广泛关注。最初，由于其高反应性，芳基和烯基三氟甲磺酸酯被用于交叉偶联反应；然而，低水分稳定性和高成本阻碍了它们的应用。后来，随着高效催化体系的发展，反应性较低的磺酸盐和膦酸盐成功地应用于交叉偶联反应。尽管它们具有更高的稳定性且易于制备，但低原子经济性仍然是它们更广泛应用的障碍。我们的团队致力于直接将丰富且易于获得的含氧化合物（如苯酚、醇、醚和羰基化合物）应用于交叉偶联反应。在本报告中，我们描述了我们在通过 C-O 键活化的过渡金属催化的新型 O 基亲电试剂的交叉偶联反应方面的最新进展。我们首先通过 Ni 催化的选择性 C-O 键断裂开发了芳基甲基醚和苄基甲基醚的甲基化。使用改进的 Ni 基催化体系，我们进一步将芳基/烯基羧酸酯和氨基甲酸酯应用于 Suzuki-Miyaura、Negishi 和 Kumada-Tamao-Corriu 反应，构建各种联芳基支架和高度取代的烯烃。为了进一步提高碳原子经济性，我们开发了二芳基硫酸盐作为单电子亲电试剂（即，两个芳基基团都用于反应）。最近，我们首次成功地实现了芳基格氏试剂与镁萘酚盐的交叉偶联反应。这些结果将芳基和苄基醚、芳基和烯基羧酸酯/氨基甲酸酯以及镁萘酚盐扩展为交叉偶联反应中的新型亲电试剂。更重要的是，这些研究有助于我们更好地理解 C-O 键的固有性质，传统上认为 C-O 键是“惰性的”，但显然具有巨大的合成潜力，只需使用适当的催化剂即可。
