Ligands have an important role to control the reactivity of transition-metal complexes by the coordination to a metal center. Since the different combination of transition metals and ligands forms the varied structures of transition-metal complexes, meticulous control over the structure of ligands makes it possible to create a novel transition-metal complex. Furthermore, the transition-metal complex thus formed can be used to develop new chemical reactions and synthesize new functional compounds; therefore, developing a new ligand is an extremely important research topic.

Among them, DPPE (Ph₂P−CH₂−CH₂−PPh₂), a bidentate phosphine ligand, is widely used to strongly coordinate to the metal center because each of the two phosphorus atoms in the molecule bonds to the metal center to form a stable five-membered ring structure. On the other hand, unsymmetric DPPE (Ar¹₂P−CH₂−CH₂−PAr²₂; Ar¹≠Ar²), which possesses electronically and sterically different substituents on both phosphorus atoms, is expected to improve catalytic activity compared to symmetric DPPE because of the ability to control the reactivity of the complex via judicious choice of the substituents. However, the synthesis of unsymmetric DPPE has been limited due to the complicated preparation processes of the starting materials, especially vinylphosphines. Hence, a robust synthetic strategy for unsymmetric DPPE from readily available starting materials is highly required.

DPPE has a structure in which phosphorus atoms are connected by a two-carbon bridge. As the carbon bridge source, we considered ethylene, which is a readily available starting material as a two-carbon source, could be a good candidate. In other words, if a reaction could be developed to introduce two functional groups containing phosphorus atoms at both ends of ethylene, it would represent a practical synthetic method for both symmetric and unsymmetric DPPEs. We verified this hypothesis using the artificial force induced reaction (AFIR) method. A backward reaction path search by adding artificial forces to decompose DPPE suggested a reaction path through a radical mechanism starting with ethylene and tetraphenyldiphosphine (Ph₂P−PPh₂). Thus, it was expected that DPPE could be synthesized if these two components could react under radical conditions.

The calculation results suggested that the excitation of tetraphenyldiphosphine from the singlet state to the triplet state had produced two phosphorus radicals spontaneously. We, therefore, thought that photoreaction conditions would be effective for experimental verification and conducted a reaction of tetraphenyldiphosphine with 10 atm of ethylene under irradiation of blue LEDs in the presence of an Ir-based photocatalyst. The reaction smoothly proceeded to afford the desired DPPE in high yield as predicted by the AFIR method. However, tetraphenyldiphosphine is easily oxidized, requiring handling in an inert atmosphere using a glove box.

As a further investigation of a more convenient and practical synthetic method, we developed the synthesis of DPPE derivatives by a three-component reaction of diphenylphosphine oxide (Ph₂P(=O)−H), ethylene, and chlorodiphenylphosphine (Ph₂P−Cl) as starting materials, requiring no glove box. In addition, by changing the substituents on the phosphine oxide and chlorophosphine, we were able to synthesize unsymmetric DPPE derivatives with electronically and sterically different substituents on both sides of phosphorus atoms. Compared to the conventional synthesis of unsymmetric DPPE, which requires complicated preparation processes of starting materials, this new method is more efficient because unsymmetric DPPE derivatives with various substituents can be synthesized by simply changing the combination of phosphine oxide and chlorophosphine.

The resulting unsymmetric DPPE derivatives could be easily converted into unsymmetric ligands upon reduction. Moreover, the obtained ligand successfully formed transition-metal complexes with various transition-metal salts. In particular, PdCl2(L1) exhibited different photophysical properties from PdCl₂(dppe).

Our research resulted in successfully obtaining new reactions by combining quantum chemical calculations based on the AFIR method with the intuition and experience of organic chemists. It should be viewed as next-generation organic synthesis research, replacing conventional trial-and-error approaches. We hope that stronger and deeper integration of calculations and experiments will lead to the development of further innovative new reactions.

• Original Paper: Nat.Commun. 2022, DOI: 10.1038/s41467-022-34546-5.
  
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