CN-122011026-A - Asymmetric bidentate phosphine ligand and synthesis method thereof

Abstract

The invention provides an asymmetric bidentate phosphine ligand and a synthesis method thereof. The ligand has a structure shown in a formula I, Wherein R 1 and R 2 are independently selected from H or C 1 C 6 alkyl, R 3 and R 4 are different substituents independently selected from C 1 C 6 alkyl, C 1 C 6 alkoxy and C 6 One of the C 15 aryl groups. Different substituents are introduced at two ends of the ligand, so that the traditional symmetrical structure is broken, and the electronic effect and the space environment can be regulated, thereby improving the selectivity and the activity of the ligand in the catalytic reaction. Meanwhile, the synthesis method of the compound is simple in process, mild in condition and simple and convenient in post-treatment, and has good scalability and industrialization potential.

Inventors

• SUI XIANWEI
• ZHU QIAOMEI
• ZENG WEN
• SONG MAN

Assignees

• 淮北师范大学

Dates

Publication Date

20260512

Application Date

20260121

Claims (10)

1. 1. An asymmetric bidentate phosphine ligand, which is characterized by having a structure shown in the following formula I: ; Wherein, R 1 and R 2 are independently selected from one of H, C 1 -C 6 alkyl; R 3 and R 4 are different substituents.
2. 2. The asymmetric bidentate phosphine ligand of claim 1, wherein the C 1 -C 6 alkyl group comprises methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl and cyclohexyl.
3. 3. The asymmetric bidentate phosphine ligand of claim 1, wherein R 3 and R 4 are selected from one of C 1 -C 6 alkyl, C 1 -C 6 alkoxy and C 6 -C 15 aryl substituents.
4. 4. The asymmetric bidentate phosphine ligand according to claim 3, wherein the C 1 -C 6 alkyl group is selected from one of methyl, ethyl, isopropyl, propyl, butyl, t-butyl, pentyl, hexyl and cyclohexyl, wherein the C 1 -C 6 alkoxy group is selected from one of methoxy, ethoxy and t-butoxy, and wherein the C 6 -C 15 aryl group is selected from 、 And Wherein R 5 and R 6 are independently selected from one of H, cl, F, methyl, methoxy, trifluoromethyl, vinyl and t-butyl.
5. 5. A method of synthesizing an asymmetric bidentate phosphine ligand according to any of claims 1 to 4, comprising the steps of: S1, placing an organic solvent in a reactor, cooling to minus 50-minus 90 ℃, respectively adding halogenated xanthene and dibenzo heterocyclic sulfur sulfoxide compounds into the reactor, further dropwise adding trifluoromethanesulfonic anhydride into the reactor, continuing to react for a certain time after the dropwise addition is completed, and obtaining a compound of a formula II after post-treatment operation; , Wherein X in the compound of the formula II is halogen, Y in the compound of the formula II is one of 0, O and S, when Y is 0, the heterocycle where Y is located is five-membered thiophene heterocycle, when Y is O, the heterocycle where Y is located is six-membered oxathiolane, and when Y is S, the heterocycle where Y is located is six-membered dithiane; S2, placing a compound of a formula II into a reactor, adding a certain amount of 2,4, 6-tris (diphenylamino) -3, 5-difluorobenzonitrile, a disubstituted phosphine compound, N-ethyldiisopropylamine and diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate into the reactor, removing air in the reactor to enable the reactor to be in an inert reaction environment, adding a certain amount of organic solvent into the reactor, and carrying out irradiation stirring reaction for a certain time by using a blue LED at room temperature to obtain the compound of the formula III; wherein said Q is one of H, cl, R 7 O-, arO-, and (R 7 ) 2 N-, and R 7 is C 1 -C 6 alkyl, ar is C 6 -C 12 aryl; S3, placing the compound of the formula III into a reactor, adding an organic solvent, cooling to minus 50-minus 90 ℃, dropwise adding a certain amount of n-butyllithium at the temperature, reacting for a certain time, adding a certain amount of disubstituted phosphine halide compound, heating the reaction temperature to room temperature, reacting for a certain time, and carrying out post-treatment operation on the reaction solution after the reaction is completed to obtain the compound of the formula I; Wherein, T is halogen.
6. 6. The synthetic method of claim 5 wherein X in the compound of formula II is selected from one of chlorine, bromine and iodine.
7. 7. The method of synthesis according to claim 5, wherein T in the disubstituted phosphine halide compound is selected from one of chlorine, bromine and iodine.
8. 8. The method according to claim 5, wherein R 7 is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl and cyclohexyl, and Ar is R 8 is selected from one of H, cl, methyl, ethyl, methoxy, trifluoromethyl and tert-butyl.
9. 9. The synthesis method according to claim 5, wherein in step S1, the post-treatment comprises pouring the reaction solution into a saturated sodium bicarbonate solution, extracting the saturated sodium bicarbonate solution with an organic solvent, and washing, drying and removing the organic solvent from the organic layer to obtain the compound of formula II.
10. 10. The synthesis method according to claim 5, wherein in step S3, the post-treatment comprises pouring the reaction solution into water, extracting with an organic solvent for several times, washing the combined organic phases with saturated saline, drying with an anhydrous desiccant, and removing the organic solvent to obtain the compound of formula I.

Description

Asymmetric bidentate phosphine ligand and synthesis method thereof Technical Field The invention relates to organophosphorus chemistry, in particular to an asymmetric bidentate phosphine ligand and a synthesis method thereof. Background Bidentate phosphine ligands play a vital role in homogeneous phase reactions catalyzed by transition metals, stabilize metal centers through chelation effects, and can finely regulate and control electron density and space environment of the metal centers, thereby remarkably influencing activity, selectivity and stability of catalytic reactions. Among the numerous bidentate phosphine ligands, xantphos (4, 5-bis (diphenylphosphine) -9, 9-dimethylxanthene) and its derivatives are a representative class of successful ligands. The structure is characterized in that a rigid xanthene skeleton is connected with two phosphorus atoms to form a natural biting angle of about 108 degrees. This unique bite angle makes Xantphos-type ligands particularly suitable for reactions requiring a large coordination angle, such as palladium-catalyzed Buchwald-Hartwig amination, carbonylation reactions, and some coupling reactions of C-S bonds and C-O bonds. The rigid structure prevents the monodentate coordination mode of the ligand and ensures the stability and unique reactivity of the catalyst. Currently, xantphos ligands, the substituents on the two phosphorus atoms of which are usually symmetrical, are widely reported in the trade and literature, for example the most classical PPh 2 groups. In addition, derivatives such as Xantphos-P (Ar) 2 (same aryl groups on both phosphorus) or Xantphos-P (Alkyl) 2 (same Alkyl groups on both phosphorus) have also appeared. While these symmetrical structured ligands have met with great success, there are inherent limitations in ligand design 1) electronic property tuning is limited in that in symmetrical Xantphos ligands, two phosphorus atoms provide identical electronic effects. This limits the ability of researchers to make asymmetric, fine-tuning adjustments to the electron density of the metal center. In some complex or sensitive catalytic cycles, the different stages of the reaction (e.g. oxidative addition, migratory insertion, reductive elimination) may differ in electron demand for the metal center and symmetrical electron supply may not be optimal. 2) Steric hindrance-adjusting homogenization symmetrical substituents means that the steric environment provided by the ligand around the metal complex is similar in the direction of the two coordination points. Such homogeneous spatial environments lack the ability to modulate when the step-wise or enantioselective control of the catalytic reaction (if combined with other chiral sources) relies on spatial shielding in a specific direction of the metal center. 3) The ligand structure and performance are insufficient, and the symmetrical design greatly limits the diversity of ligand libraries derived based on Xantphos frameworks. Although it is possible to modulate by changing the substituents on the xanthene backbone or the para-substituents on the phosphorus, the synergistic effects or new properties that may be produced by the differential combination of substituents on the two phosphorus atoms have not been explored and exploited. The method is essentially a synthetic study of bidentate phosphine ligands, and a great deal of research effort has been put into the field of research. Conventional methods generally rely on nucleophilic substitution reactions （a) I. Wauters, W. Debrouwer, C. V. Stevens, Beilstein J Org. Chem. 2014, 10, 1064-1096; b) H. 2-Yorimitsu, Beilstein J Org. Chem. 2013, 9, 1269-1277.）. of halogenated phosphines with air-sensitive organometallic reagents and have also reported the formation of triphenylphosphine bonds using transition metal catalyzed or photoinduction strategies starting from aryl halides and air-sensitive secondary phosphines (w.liu, h.hou, h.jin, s.huang, w.ou, c.su, org, lett.2023, 25, 8350-8355). Arylphosphines can also be obtained by reduction of the corresponding phosphine oxides using an excess of sensitive or expensive reducing agents, such as LiAlH 4、HSiCl3 (j. Xue, y. S. Zhang, z. Huan, j. D. Yang, j. P. Cheng, j. Am. chem. Soc. 2023, 145, 15589-15599). There have also been other studies devoted to the synthesis of these important structures. However, these strategies often have limitations in terms of synthesis scope, selectivity, and compatibility with different functional groups. In this context, reductive radical cross-electrophilic coupling has become a promising strategy for constructing triphenylphosphine, without the use of sensitive organometallic substrates or secondary phosphine reagents. But fewer such cases may be due to the challenges of generating and converting aryl radicals by conventional strategies. In 2006, oshima and Yorimitsu reported a novel reductive radical phosphine reaction using tris (trimethylsilyl) silane as the reducing agent to