Zhang's group from the College of Chemistry and Molecular Engineering, Peking University has recently published two review papers. One is titled “Recent Progress on the Functionalization of White Phosphorus in China” in the journal National Science Review (Xinlei Huangfu, Zhongzhen Wang, Yu Chen, Junnian Wei, Wei Liu,* and Wen-Xiong Zhang,* Natl. Sci. Rev. 2024, doi: org/10.1093/nsr/nwae162.). The other is titled “Chiral Bisphosphine Ph-BPE Ligand: A Rising Star in Asymmetric Synthesis” in the journal Chemical Society Review (Peifeng Mei, Zibin Ma, Yu Chen, Yue Wu, Wei Hao, Qinghua Fan, and Wen-Xiong Zhang,* Chem. Soc. Rev. 2024,doi: org/10.1039/d3cs00028a.).
Organophosphorus compounds (OPCs) are among the most extensively studied and widely applied element organic compounds. The field of organophosphorus chemistry has remained vibrant and at the forefront of chemical research for over a century. These compounds play a crucial role in synthetic chemistry, with at least three Nobel Prizes in Chemistry closely related to the discovery of organophosphorus reagents, phosphine ligands, and phosphorus-containing catalysts. For instance, the chiral bisphosphine ligand BINAP was awarded the 2001 Nobel Prize in Chemistry for its application in asymmetric catalysis. Additionally, OPCs have extensive applications in various fields such as pharmaceuticals, pesticides, life sciences, extractants, flame retardants, food additives, electrolytes, and detergents (Fig.1A), where they play an irreplaceable role. The phosphorus in these compounds primarily originates from white phosphorus (P4). However, the traditional route from P4 to OPCs is complex and lengthy. In most cases, highly toxic intermediates such as PCl3 and PH3 are first synthesized, which are then further exploited to produce OPCs. This synthetic process involves toxic, highly corrosive, and flammable reaction conditions, leading to the significant environmental pollution (Fig.1B).
Fig.1 The significance and synthetic pathways of organophosphorus compounds.
Considering the inherent issues in traditional methods, the direct synthesis of OPCs from P4 holds significant scientific importance and practical application value. Currently, over 30 research groups worldwide are engaged in the activation and transformation of P4. China contributes more than 70% of the global production of P4. However, research in the field of P4 activation and transformation in China is relatively lagging. The research group led by Wen-Xiong Zhang began working in this area in 2014, and their first paper titled "Direct Synthesis of Phospholyl Lithium from White Phosphorus" was published in 2016. Since then, they have reported a series of works on the direct functionalization of P4 to form P-C bonds (Chem. Eur. J. 2023, 29, e202302289; Inorg. Chem. 2023, 62, 12009; Green Synth. Catal. 2023, 4, 330; Sci. China Chem. 2022, 65, 322; J. Am. Chem. Soc. 2019, 141, 6843; Angew. Chem. Int. Ed. 2017, 56, 15886; Angew. Chem. Int. Ed. 2016, 55, 9187.). In the past five years, more than 10 research groups in China have been involved in the research on the activation and transformation of P4, including Zhenfeng Xi's group from Peking University, Yufen Zhao/Guo Tang's group from Xiamen University, Xigeng Zhou's group from Fudan University, Liu Leo Liu’s group from Southern University of Science and Technology, Liang Deng’s group from the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Wenshan Ren’s group from Southwest University, Congqing Zhu's group from Nanjing University, Zhenbo Mo's group from Nankai University, and Xin Xu's group from Soochow University, and so on. In recent years, Chinese research teams have made significant progress in the direct activation and functionalization of P4, directly constructing various chemical bonds such as P-C, P-N, P-O, and P-S through new synthetic methods (Fig.1C), achieving efficient conversion from P4 to OPCs, reducing the generation of harmful by-products, and improving atom economy. Based on this, the research group led by Wen-Xiong Zhang recently summarized these findings in the journal National Science Review (Fig.2).
Fig.2 Achievements of Chinese researchers in the direct functionalization of P4.
Despite numerous accomplishments, the activation and transformation of P4 remain challenging. The high electrophilic reactivity of the P4 molecule, the low selectivity after cleavage of the P-P bond, and the inefficient conversion of P-atoms within P4 are issues that limit the further development of P4 chemistry. The review concludes by envisioning future research directions in the activation of P4. These include a deeper investigation into the complex mechanisms of P4 bond cleavage, the development of new reaction systems, the use of electrochemical methods, the combination of C-H bond activation with P4 transformation, and the application of machine learning to design more efficient reaction pathways and optimize reaction conditions. The long-term goal of this review is to inspire more researchers to engage in the activation and transformation of P4, to promote environmentally friendly and sustainable methods of P4 activation, and to meet the future society's needs for industrial processes that do not rely on environmentally unfriendly chlorination routes.
It is well-known that the synthesis of commonly used chiral phosphine ligands typically involves the use of PCl3, which is a lengthy process with high costs, and results in the release of chloride ions or large amounts of acidic substances, posing safety and environmental concerns. To date, the literature has not documented any method for constructing chiral phosphine ligands from P4 without chlorination—a completely new approach. In 2016, Prof. Wen-Xiong Zhang and colleagues reported the synergistic activation of P4 by a bimetallic reagent to afford phospholyl lithiums without chlorination, achieving nearly 100% yield. This method represents the first potentially practical chlorination-free approach. Consequently, they innovatively proposed the use of this method to synthesize chiral 1,2-bis(2,5-diphenylphospholano)ethane (Ph-BPE).
Chiral Ph-BPE is a class of optimal organic bisphosphine ligands withC2-symmetry. Ph-BPE with its excellent catalytic performance in asymmetric synthesis has attracted much attention from chemists, gaining increasing popularity and becoming into one of the most commonly used organophosphorus ligands, especially in asymmetric catalysis. Over two hundred examples have been reported since 2012.In general, Ph-BPEexhibits the following characteristics that make it superior in a wide range of reaction categories: (i) the P atom of Ph-BPE is connected with three alkyl groups, resulting in a highly electron-rich environment; (ii) among the BPE ligands, Ph-BPE with 2,5-substituents exhibits the largest steric hindrance and rigidity; and (iii) flexible linking groups: ethylene has the length of two carbons, ensuring that the P-M-P has a suitable angle when coordinating with the metal. Based on this, Wen-XiongZhang’s group has recently summarized the discovery, synthesis, and application of these well-known privileged chiral phosphine ligands in asymmetric synthesis in Chem. Soc. Rev. (Fig. 3).
Fig.3 Application of chiral Ph-BPE ligands in asymmetric catalytic reactions
In summary, the chlorination-free method for directly constructing OPCs from P4 is an urgent need in current phosphorus chemical engineering. This groundbreaking synthesis will provide a scientific foundation and technical support for the entire phosphorus chemical industry, leading the international development of phosphorus chemistry. Doctoral candidates XinleiHuangfu, ZhongzhenWang, and Yu Chen are the co-first authors of the review in Natl. Sci. Rev., with the corresponding authors being Dr. Wei Liu and Prof. Wen-Xiong Zhang from Peking University. Dr. Peifeng Mei is the first author of the review in Chem. Soc. Rev., with Prof. Wen-Xiong Zhang as the corresponding author. These works were supported by the National Natural Science Foundation of China, the National K&D Program of China, and the Beijing National Laboratory for Molecular Sciences (BNLMS).
Link: https://doi.org/10.1093/nsr/nwae162;https://doi.org/10.1039/d3cs00028a.
