Introduction:

Glufosinate ammonium, also known as glufosinate, boasts the chemical name 4-[hydroxy(methyl)phosphinoyl]-DL-homoalanine. Developed by the renowned German company Hoechst, this non-selective herbicide is lauded for its efficiency, broad-spectrum capability, and low toxicity. While the majority of commercially available glufosinate ammonium is currently a racemic mixture, it is essential to note that only L-glufosinate ammonium exhibits potent herbicidal activity. Despite the maturity of the production process for DL-glufosinate ammonium, research on L-glufosinate ammonium remains in the laboratory stage, with industrialization yet to be realized. Therefore, the investigation and development of L-glufosinate ammonium production processes hold significant importance.

Global Methods for L-Glufosinate Ammonium Preparation:

Currently reported methods for synthesizing L-glufosinate ammonium primarily fall into two categories: chemical methods and biological methods. Chemical methods involve utilizing natural amino acids as chiral sources or constructing chiral centers asymmetrically. However, these methods often suffer from drawbacks such as high costs and low optical purity. On the other hand, biological methods encompass biodegradation and bioasymmetric synthesis. Biodegradation utilizes DL-glufosinate ammonium or its derivatives as substrates, relying on microbial degradation for the separation of specific configurations. Bioasymmetric synthesis, alternatively, employs 2-carbonyl-4-(hydroxymethylphosphinoyl)butanoic acid as a substrate, catalyzed by an enzyme system to produce L-glufosinate ammonium. While biological methods boast mild reaction conditions, the strict growth environment requirements for microbial enzymes and the generation of substantial wastewater pose challenges.

Innovative Approach Using Chiral Auxiliary:

Drawing from existing literature [11-14], this study introduces a groundbreaking method employing (2S)-N-(2-benzoyl-4-chlorophenyl)-1-benzyl-2-pyrrolidinecarboxamide hydrochloride as a chiral auxiliary. In this innovative process, DL-glufosinate ammonium forms a coordination compound with the chiral auxiliary and metal ions under the influence of an inorganic base. A crucial aspect of this method is the reversal of D-glufosinate ammonium configuration, leading to the production of L-glufosinate ammonium. Subsequently, the complex undergoes hydrolysis, resulting in the desired L-glufosinate ammonium, while simultaneously enabling the recycling of the chiral auxiliary and metal salt.

Experimental Section:

1. Instruments and Reagents:
 - Bruker AV300 NMR spectrometer, Shimadzu LC-16 high-performance liquid chromatography, Bruker Esquire 3000 Plus ESI/MS mass spectrometer, ZF-I UV analyzer. All reagents used in the experiment are commercially available analytical pure reagents.

2. Synthesis of Intermediate 1 (1-N-benzyl-L-proline):

   - In a 500 mL three-neck flask, a meticulous process involving methanol, sodium hydroxide, and L-proline results in Intermediate 1 with a 91.0% yield.

3. Synthesis of Intermediate 2 ((2S)-N-(2-benzoyl-4-chlorophenyl)-1-benzyl-2-pyrrolidinecarboxamide):

   - A carefully controlled reaction involving chlorobenzene, phosphorus pentachloride, and 5-chloro-2-aminobenzophenone produces Intermediate 2 with a 95.3% yield.

4. Preparation of L-glufosinate ammonium:

   - The final synthesis step utilizes sodium hydroxide, methanol, DL-glufosinate ammonium, hexahydrated nickel chloride, and Intermediate 2, achieving a 94.5% yield with an ee value of 96.7%.

Results and Discussion:

1. Synthesis of Chiral Auxiliary:

- This route offers mild reaction conditions and straightforward post-treatment. The substitution of chlorobenzene for bromobenzene and the use of sodium hydroxide as the acid-binding agent in L-proline alkylation contribute to reduced production costs. Furthermore, the acylation reaction of Intermediate 1 with phosphorus pentachloride leads to the direct precipitation of Intermediate 2 as a hydrochloride salt, eliminating the need for additional acid-binding agents. Notably, by-products such as phosphorus oxychloride are recycled.

2. Synthesis of L-glufosinate ammonium:

- The study delves into the impact of different nickel salts on reaction results, with nickel chloride emerging as the most effective, achieving an optical purity of over 96%. Additionally, liquid chromatography analysis provides detailed insights into the retention times of L-glufosinate ammonium and D-glufosinate ammonium.

Conclusion:

This research contributes a novel and efficient approach to L-glufosinate ammonium synthesis, showcasing a 90% yield with an impressive ee value of 96.7%. The method, utilizing a chiral auxiliary and coordination compound formation, presents a viable path for industrial-scale production, bridging the gap between laboratory research and practical applications.