Perkow

The reaction of aldehydes with carbon tetrachloride in the presence of excess tris(dimethylamino)phosphine has been used to prepare vinyl dihalides in yields of 50—70%. It is suggested that the reaction takes place via an intermediate salt (77), although the formation of this salt seems more likely to be analogous to the Perkow reaction than to involve attack on oxygen. 

While a "Perkow-route"71 81 for product formation generally ensues when a-halocarbonyl substrates are challenged with Michaelis-Becker reagents,173-175 ethyl 4-bromoacetylaceto-nate provides a simple substitution product.176 Simple substitution occurs also with a-haloesters and a-halophospho-nates.177/178... 

Perkow, E., Ullerich, K., and Meyer, F., New phosphoric ester with miotic activity, Naturwissenschaften, 39, 353, 1952. 

Borowitz, I.J., Yee, K.C., and Crouch, R.K., Determination of stereochemistry in vinyl phosphorylated species by nuclear magnetic resonance shift reagents. Revised mechanistic pathways for the Perkow reaction, /. Org. Chem., 38,1713, 1973. 

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. 

Winkler, T. and Bencze, W.L., Perkow reaction induced C,C-bond formation, Helv. Chim. Acta, 63, 402, 1980. 

The enoxyphosphonium salts are relatively stable, even if they are very sensitive to solvolysis they have been considered as the intermediates in Perkow s reaction462. A very similar reaction leads to enaminophosphonium salts (or to iminophosphonium salts when there is a subsequent isomerization possibility of the double bond by prototropy)463 (reaction 132). 

Because of the Perkow reaction, the above route for the production of ketophosphonates and phosphonopyruvates was abandoned. By coupling a-copperalkylphosphonates with acyl chlorides, we have been able to produce in one step ketophosphonate correctly functionalized as well as phosphonopyruvates in good yield and high purity (6). Rl... 

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). 

We have now carried out crossover experiments in which the reaction of trimethyl phosphite with a mixture of differently substituted chloro- and bromoace-tophenones (e.g. C,H,.C0CH2C1 and p-MeC,H.C0CH2Br) affords a mixture ofproducts whose composition shows that halogen exchange has occurred. In other words,the ratio of Perkow to Arbuzov products is that which would be expected if C-H,-COCH2Br and p-MeCgH COCH l were also present in thereaction mixture 5 mol% in benzene, 8 mol% in chlorobenzene, 23 mol% in acetonitrile). ... 

To obtain more information on the nature of the quasiphosphonium intermediates involved in these systems we have studied the reactions gf sterically hindered neopentyl esters by means of 1P nmr spectroscopy. Trineopentyl phosphite and a-bromoacetophenone gave rise to a peak at +41 ppm due to the ketophosphonium intermediate 3 (R = Me.CCH, R = Ph X = Br ) within half an hour of mixingJthe reactants in acetone-dfi at 27 °C ( p nmr shifts are relative to 85% H-PO. down-field positive). Peaks due to the ketophospnonate 4 +19 ppm and the vinyl phosphate 7 (-7 ppm) were also observed (compound 4 and 7 have satisfactory elemental analysis and spectroscopic data ). The concentration of the intermediate reached a maximum after about two hours when it was precipitated from acetone solution by the addition of anhydrous ether to give white crystals of trineopentyloxy (phenacyl)phosphonium bromide, identified by elemental analysis and nmr spectroscopy ( XP 6+41, in CDCl ). When redissolved in acetone-dg, deuterochloroform, acetic acid, or acetic acid-acetone mixtures, the intermediate decomposed to yield keto-phosphonate 4 but none of the vinyl phosphate 6 (Perkow product). Nor was the course of reaction affected by the addition of chloride ion or of a-chloro-acetophenone in acetonitrile. 

Both reactions involve nucleophilic attack of tricoordinated phosphorus on tetrahedral carbon and show all the characteristics of non-polar reactants combining through polar transition states although the solvent effects are sometimes quite modest.— Subsequent studies have demonstrated nucleophilic attack on activated alkenes,Z activated alkynes,Z the carbonyl groupZ-Z and halogen , whilst in the Perkow reaction (eqn. 1) all four possible sites in... 

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 ... 

B A. Arbusov, Michaelis-Arbusov- und Perkow-Reaktionen, Pure Appl. Chem. 9, 307 (1964). 

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