97 / 2023-09-28 20:44:25

Solvent-Free Synthesis of Alkylphosphonates and Arylphosphonates via the Michaelis–Arbuzov Rearrangement

Alkylphosphonates; Arylphosphonates; Michaelis–Arbuzov rearrangement; Brønsted acid-catalyzed; Palladium-catalyzed; Solvent-free

New Technologies in Phosphorus Chemistry > 1) New reagents and methods in organophosphorus Chemistry

Michaelis-Arbuzov reaction, the formation of the P(V) phosphonates RP(O)(OR)₂ by the rearrangement of the P(III) phosphites via a combination of (RO)₃P/RX, was discovered more than 120 years ago. Because the starting materials used in the reaction are cheap and readily available, and also because the reaction process is simple, this reaction has been, ever since, the most famous and frequently used premier synthetic tool for the preparation of phosphonates RP(O)(OR)₂, that have important applications in organic synthesis, flame retardancy, material chemistry and biological chemistry. However, drawbacks of this method such as the use of toxic alkyl halides, harsh conditions, heavy pollution, low efficiency, and release of toxic gas are also obvious. In addition, the classic Michaelis-Arbuzov reaction is essentially restricted to the preparation of aliphatic phosphonates RP(O)(OR)_2.

Therefore, we developed two methods to afford alkylphosphonates or arylphosphonates from the isomerization of phosphites via the Michaelis-Arbuzov rearrangement. Thus, in 2019, we reported the Brønsted acid-catalyzed C-O cleavage reactions of trialkyl phosphites selectively leads to the production of alkylphosphonates, demonstrating a mild and efficient halide-free alternative for the Michaelis-Arbuzov reaction. Mechanistic studies and the results of bulky substrates showed that the reaction perhaps takes place via a monomolecular mechanism. This method is general in substrate scope as it can be readily extended to phosphonites and phosphinites for preparation of the corresponding H-phosphinates, alkylphosphinates, H-phosphine oxides, and alkylphosphine oxides. Unfortunately, like the classic Michaelis-Arbuzov reaction, this new reaction is also only applicable to alkyl phosphites, and no rearrangement took place at all with (ArO)₃P. During the investigation on the aryl phosphites, we found that a unique palladium-PhX (X= OTf, I) was able to catalyze the rearrangement of (ArO)₃P to ArP(O)(OAr)₂, to afford the corresponding rearrangement products in good to excellent yields. This new catalytic method is also general in substrate scope as it can also be readily extended to aryl phosphonites and phosphinites to prepare the corresponding arylphosphinates and phosphine oxides.