Acylphosphonates oxidation

Recently, alternative methods for preparation of acylphosphonates based on oxidation of easily prepared a-hydroxy- [10,11] and a-diazo phosphonates [12] have been developed. A variety of oxidation methods Mn02, PCC (pyridinium chlorochromate), PDC (pyridinium dichromate), Pfittzner-Moffatt, Swern oxidation have been applied to a-hydroxy phosphonate substrates [13-16]. 

The Michaelis-Arbuzov reaction works well for the less complex aroyl and alkanoyl chlorides, where purification by distillation is possible. Moreover, there has been less success in the preparation of oc,P-unsaturated acylphosphonates, where multiple addition products are often observed. Recourse has been found in an attractive route that entails oxidation of dialkyl 1-hydroxyalkyl- or 1-hydroxyaryIphosphonates produced by nucleophilic addition of dialkyl phosphites to carbonyl compounds under basic conditions (Pudovik reaction). Alkali metal salts of dialkyl phosphites are currently used in the Pudovik reaction, and the more common procedure of generating the anion involves the addition of a small amount of alcoholic alkoxide ion to the reaction mixture. Neutral amines represent an alternative to the use of anionic bases. In recent years, the use of solid-phase materials as basic catalysts has been successfully developed (Scheme 7.7). One system involves the addition of basic alumina to the carbonyl compound and dialkyl phosphite the other involves the addition of KF or CsF to the mixture of carbonyl compound and dialkyl phosphite. - Such a process for generating dialkyl 1-hydroxyalkyIphosphonates is very flexible and accommodates a large variety of carbonyl compounds. 

The treatment of diethyl aroylphosphonates with 3-chloroperoxybenzoic acid yields diethyl aroyl phosphates (oxygen insertion) in 70-85% yields together with smaller amounts of mixed carboxylic anhydrides, ethyl benzoate and diethyl hydrogenphosphate (Scheme 31). The main reaction is a typical Baeyer-Villiger oxidation, applied here to an acylphosphonate The reaction generally has little value in the synthesis of acyclic mixed anhydrides, which are easily obtained by other procedures, but it is of value in some slightly modified but specific cases as, for example, in the synthesis of compounds in the 2,3-oxaphosphabicyclo[2.2.2]octane series (Section III.A.2). The 1 1 adducts of H-phospholes and A-phenylmaleimide (177) or dimers of the same phospholes (178 R =... 

A recent paper reports the oxidation of benzylic a-hydroxyphosphonates to aroylphos-phonates in good yields, by refluxing them with 10 equiv. of Mn02 in toluene The same paper reports that other oxidizing agents, including pyridinum chlorochromate and dichlorodicyanobenzoquinone (DDQ),or the Swem method are also applicable for the oxidation of benzylic a-hydroxyphosphonates to benzoylphosphonates. This approach to acylphosphonates was found, however, to be limited to tert-huty esters. ... 

The Baeyer-Villiger oxidation of dialkyl acylphosphonates was shown to provide a convenient entry to acylphosphates (equation 81) . The reaction has been shown to constitute a migration of dialkoxyphosphonyl group to an electron-deficient oxygen . 

A series of sodium salts of acetylphosphonic acid as potent inhibitors of E. coli PDHc was reported by Kluger and Pike in 1977 [40]. Ten years later, on the basis of work of Kluger and Pike, further research on PDHc inhibitor was conducted by Baillie et al. in 1988 [2]. Plant PDHc El (EC 1.2.4.1) was used as the target to design a herbicide based on the understanding of key metabolic processes. In these metabolic processes, oxidative decarboxylation of pyruvate into acetyl coenzyme was catalyzed by PDHc El. More than 50 alkyl acylphosphonates, acylphosphinates, and their salts as mechanism-based inhibitors of PDHc were synthesized. Then-inhibition against pea PDHc was evaluated. Some of them were found to be very powerful inhibitors (Table 1.5) [2]. 

Acylphosphine oxide and acylphosphonates with different structures have been used as photoinitiators for free-radical-initiated photopolymerization (see Table 6). 

---