Phosphite Perkow reaction

Enol phosphates (332) have also been obtained reductive debromination of the 2a-bromo-3-ketone with triethyl phosphite (Perkow reaction) gave the... 

Sekine, M., Okimoto, K., Yamada, K., and Hata, T., Silyl phosphites. 15. Reactions of silyl phosphites with a-halocarbonyl compounds. Elucidation of the mechanism of the Perkow reaction and related reactions with confirmed experiments, /. Org. Chem., 46, 2097, 1981. 

In spite of many previous studies on the mechanisms by which trialkyl phosphites interact with a -halogenocarbonyl compounds, the reactive intermediates which lead to ketophosphonate (Arbuzov reaction) and to vinyl phosphate (Perkow reaction) have in no cases been clearly identified. It is generally believed (JL), however, that the Arbuzov product 4 results from initial attack by phosphorus at the cf-carbon atom, whereas the Perkow product 7 is formed by initial attack at the carbonyl carbon atom, followed by migration of phosphorus from carbon to oxygen (Scheme 1). 

Gramine - 3-(dimethylaminomethyl)indole (14) - is a readily obtainable derivative of indole and is produced with a quantitative yield by the Mannich reaction. In [19] it was phosphorylated with diethyl chlorophosphite. 3-(Dimethylaminomethyl)-l-(triethoxyphosphito)indole (15) was obtained also by the method in [20] using diethyl penten-3-on-2-yl phosphite. Compound 15 readily adds sulfur with the formation of the corresponding gramine 1-thiophosphate 16 and reacts with chloral according to the scheme of the Perkow reaction, forming phosphate 17 ... 

Protocol 2 produces the protected fi-formylphosphonate 12 f)-ketophospho-nates may also be synthesized by other methods,23 however, they may not be prepared in unprotected form by the Michaelis-Arbuzov reaction because the Perkow reaction, in which an a-haloaldehyde or ketone and a trialkyl phosphite yield an enol phosphate (e.g. 13, Scheme 5,24 i.e. [P—O] bond formation), competes and frequently dominates (see Section 4). Conversely halocarboxylic acid derivatives (e.g. see Table 7.1, entry 3) and acyl halides (see Protocol 3) react well in the Michaelis-Arbuzov reaction to yield useful functionalized phosphonates. fi-Ketophosphonates are useful reagents for the synthesis of a,fi-unsaturated carbonyl compounds by the Horner-Wadsworth-Emmons reaction,3,4 25 and have other applications.23... 

In the Perkow reaction, a trialkyl phosphite reacts with an a-halo-aldehyde or -ketone to yield an enol phosphate (i.e. [P—O] bond formation, e.g. Scheme 5).76 a-Haloaldehydes react cleanly but with a-haloketones the Michaelis-Arbuzov reaction usually competes with the product distribution depending on the reaction... 

Dialkyl phosphites and their metal salts seldom undergo the Perkow reaction with a-halo-aldehydes or -ketones but usually yield a-hydroxy- and/or epoxy-phosphonate esters (i.e. Pudovik reaction products, cf. Section 6).78... 

The phosphate is prepared by the Perkow reaction of ethyl trichloroacetate and triethyl phosphite (83% yield). 

Several interesting approaches to the synthesis of /I-ketophosphonates have recently been described. Typically, standard Arbuzov synthesis of /1-ketophospho-nates is unsatisfactory due to a competing Perkow reaction [51]. However, y,d-unsaturated /1-ketophosphonates are obtained in high yield via Arbuzov reaction of triethyl phosphite with a-iodoenones, readily available from tertiary allenic alcohols [52]. Another successful example of an Arbuzov-based approach involves reaction of bromoacetylated polystyrene with triethyl phosphite, which provided immobilized /J-ketophosphonate in excellent yield [53]. In another approach, the lithio derivative of dimethyl methylphosphonate was reacted with Weinreb amide to obtain the corresponding /J-ketophosphonate [54]. a,a-Diflu-oro-a-ketophosphonates have been synthesized via a cerium-mediated route... 

Perkow reaction. Formation of enol phosphates on treatment of a-halocarbonyl compounds with trialkyl phosphites. 

As might be expected, keto-sugar acetates undergo the Perkow reaction with trimethyl phosphite to give a mixture of enol phosphates (27) and (28). In other cases the products appear to be dependent on the leaving group, and the Perkow products... 

Possibly the most frequently used and most widely known phosphonylated aldehyde is diethyl l-formylmethyIphosphonate. A vaiiety of methods for the preparation of this aldehyde are reported in the literature. The oldest employs tlie Michaelis-Arbuzov reaction between triethyl phosphite and bromoacetaldehyde diethyl acetal, which yields diethyl 2,2-diethoxyethylphosphonate on heating to 160°C (Scheme 5.5). Subsequent acid hydrolysis gives diethyl 1-formylmethylphosphonate. The aldehyde function requires protection because it is known that a-haloaldehydcs react with trialkyl phosphites in a Perkow reaction affording dialkyl vinylphosphates isomeric with the expected phosphonates. " ... 

Trimethyl phosphite does not react with chloroacetyl chloride through a Michaelis-Arbu-zov/Perkow reaction sequence. It gives an acylpseudophosphonium salt, which, in turn, reacts readily with trimethyl phosphite to give a new adduct. Subsequent warming affords dealkylation to give the final dimethyl l-(dimethoxyphosphinyloxy)vinylphosphonate (Scheme 7.3). More interesting from the mechanistic standpoint is the use of diethyl trimethylsilyl phosphite. In reaction with chloroacetyl chloride at 30°C, the initial adduct loses MejSiCl rapidly to give diethyl 2-chloroacetylphosphonate in 37% yield." ... 

With the presence of more than one halogen atom in the a-position of the halo ketone, the formation of 2-oxoalkylphosphonates becomes more difficult, and the reactions proceed exclusively according to the Perkow reaction. Thus, dichloromethyl, dibromomethyl, and tribromomethyl methyl ketones, in reaction with trialkyl phosphites, lead to the corresponding vinyl phosphates... 

Miller, J.A., Reactions of dimethyl phosphite with tetracyclone, Tetrahedmn Lett., 11, 3427, 1970. Borowitz, I.J., Firstenberg, S., Borowitz, G.B., and Schuessler, D., Organophosphorus chemistry. Part 17. Kinetics and mechanism of the Perkow reaction, 7. Am. Chem. Soc., 94, 1623, 1972. 

Hudson, H.R., Matthews, R.W., McPartlin, M., Pryce, M.A., and Shode, O.O.. Quasiphosphonium intermediates. Part 7. The preparation of trinorborn-l-yl phosphite and its reactions with halogeno compounds. Stable intermediates of the Arbuzov and Perkow reactions and then sU uctural characterization by X-ray diffraction, NMR spectroscopy, and fast-atom-bombardment mass spectrometry, J. Chem. Soc., Perkin Trans. 2, 1433, 1993. 

Perkow reaction.1 Perkow2 noted that a-halo aldehydes and ketones react with trialkyl phosphites to give dialkyl vinyl phosphates ... 

The Perkow reaction of triethyl phosphite with 2-chloroethyl trichloroacetate gives 0,0-diethyl-0-[l-(chloroethoxy)-2,2-dichlorovinyl] phosphate (69), introduced under the trade name Forstenon (Sallmann, 1952). 

Not only the a-polyhalogen aldehydes, but also the oc-polyhalogen ketones give the Perkow reaction with trialkyl phosphites, whereby vinyl phosphates are formed containing one chlorine atom less. In the reaction of triethyl phosphite with dichloromethyl-2,4-dichlorophenylketone, 0,0-diethyl-0-[l-(2,4-dichlorophenyl)-... 

Polish research workers prepared several analogues of chlorfenvinphos in order to develop a derivative with similar action but less toxic. The result of this work was 0,0-diethyl-0-[2-bromo-1 -(2,4-dichlorophenyl)vinyl] phosphate (bromfenvin-phos, 72). It is prepared by the Perkow reaction with triethyl phosphite and dibromoethyl-2,4-dichlorophenyl ketone (Fulde et al., 1974 Zwierzak, 1974). 

Based on the research work of Stiles (1952), one of the most important phosphorus ester insecticides, 0,0-dimethyl-0-[(l-methyl-2-carbomethoxy)vinyl] phosphate (mevinphos, 73) was introduced in 1957 under the trade name Phosdrin . It is prepared by the Perkow reaction from trimethyl phosphite and methyl a-chloroacetoacetate. 

The Perkow reaction has been used to generate a wide range of vinyl phosphates. Reaction of trialkyl phosphites with a-halogeno-ketones provide vinyl phosphates.1-5 Alkenes are produced via reduction of the dialkyl enol phosphate using either sodium or lithium in liquid ammonia. 

In 1952 Perkow discovered a new type of rearrangement in which trialkyl phosphites react with a-aldehyde.6,7 This anomalous Arbuzov reaction, which resulted in the formation of dialkylvinylphosphates, subsequently became known as the Perkow reaction. 1 The reaction of trialkyl phosphites with alkyl halides (Arbuzov reaction) proceeded to yield dialkoxy alkyl phosphonates.8 The alkyl halide undergoes a nucleophilic displacement to yield the nonisolable alkyl trialkoxy phophonium halide.8 The halide can then attack an alkoxy group to give phosphonate ester and RX. An increase in temperature favors the Arbuzov reaction leading to phosphonates (Sn2 displacement). 

Many different mechanisms have been proposed for the Perkow reaction.2-4 It involves nucleophilic attack of the phosphite at the carbonyl carbon and affords a zwitterionic intermediate 5 which rearranges to form a cationic species 6 that subsequently dealkylates to give the corresponding vinyl phosphate 7. The conversion proceeds via a Michaelis-Arbuzov cleavage of an alkoxy group by halide ion as shown. 

Diethylphosphite and thiophosphite anions react in a modified Perkow reaction to yield the enol phosphite and thiophosphates (13). (EtO POK is prepared from diethylphosphite and r-BuOK (X = O, 72%, X = S, 42%). 

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