An Efficient α-Phosphoryloxylation of Ketones

An efficient α-phosphoryloxylation of ketones has been developed. When ketones were treated with (diacetoxyiodo)benzene and phosphates in CH2Cl2 at room temperature, the α-phosphoryloxylaction of ketones was easily be carried out, providing the ketol phosphates in good yields.


Introduction
Hypervalent iodine reagents have found broad application in organic chemistry and nowadays frequently used in synthesis due to they are nonmetallic oxidation reagents and avoid the issues of toxicity of many transition metals commonly involved in such processes [1][2][3][4][5][6][7][8][9][10].They offer high potential for the improvement of known reactions not only from the environmental point of view，they are also potentially interesting reagents for the development of completely new synthetic transformations.Among hypervalent iodine reagents, [hydroxy (tosyloxy)iodo]benzene (Koser's reagent) is the most popular and useful reagent for the direct α-tosyloxylation of ketones, and with which the α-tosyloxylation of ketones has been extensively studied especially in recent years [11][12][13][14][15][16][17].However, to our knowledge, the analogue reaction of ketones for α-phosphoryloxylation has been rather limited and only two methods for preparation of the important ketol phosphates have been known.Using the hypervalent iodine reagent, [hydroxyl ((bis(phenyloxy) phphoryl)-oxy)iodo]benzene to react with ketones was the main method which was reported by Koser's group in 1988, in this process hypervalent iodine reagent must be pre-prepared from (diacetoxyiodo)benzene and diphenyl phosphate [18][19].The reaction of the prepared hypervalent iodine reagent with terminal alkynes in aqueous MeCN was another protocol for preparation of ketolphosphates [20].In order to extend the scope of αphosphoryloxylation of ketones and to prepare more ke-tol phosphates, the development of a simple, mild and efficient α-phosphoryloxylation of ketones is a muchsought process.Herein we would like to report an efficient one-pot α-phosphoryloxylation of ketones and a series of ketol phosphates have been prepared in good yields.

Results and Discussions
At the beginning, we investigated the "one pot" procedure to improve Koser's method due to the preparation of [hydroxyl((bis(phenyloxy)phosphoryl)oxy)iodo]bezene and its reaction with ketones were separated in two steps.When one equivalent of (diacetoxyiodo)benzene (DIB), diphenyl phosphate and acetophenone were mixed in CH 2 Cl 2 at room temperature and stirred for 24 h, the desired product of α-phosphoryloxyl acetophenone was separated in 38% yield after separation.Then, a series of experiments were performed on the reaction of (diacetoxyiodo)benzene, diphenyl phosphate and acetophenone to determine the suitable reaction conditions (Scheme 1), the results are summarized in Table 1.
The results indicate that the yield depended on solvent and CH 2 Cl 2 was found to be the most preferred (entries 1-5).When (diacetoxyiodo)benzene and diphenyl phosphate reached to two equivalents, the yield was increased to 43% (entry 6); while two equivalents of acetophenone were used to reacted with one equivalent of (diacetoxyiodo)benzene and diphenyl phosphate, the reaction got the higher yield of 48% (entry 7).We found that the product of α-phosphoryloxyl acetophenone was partly decomposed in separation and the yield was decreased much, then we used 1 H NMR technique to show the true yield and after 24 h the reaction reached the highest yield of 80% (entries 8-13).
Under the optimum reaction conditions, the reaction of a series of ketones ( 1) with (diacetoxyiodo)benzene and phosphate (2) in CH 2 Cl 2 at room temperature was investigated (Scheme 2), and several ketol phosphates (3) were obtained which all were characterized by 1 H NMR, 13 C NMR, IR and MS spectra, the results are summarized in Table 2.It is shown that the α-phosphoryloxylaction of ketones was easily carried out at room temperature and complete in 24 h, most provided the corresponding ketol phosphates in good to excellent yields.In comparison with other ketones, β-diketone 1e and 1f usually needed much less time in the reaction and got the products in excellent yields due to the high activity of α-hydrogen (entries 5-6,8).
The proposed mechanism for the α-phosphoryloxy-laction of ketones is similar to the literature procedure [21], which is shown as follows (Scheme 3).

Experimental
IR spectra were recorded on a Thermo-Nicolet 6700 instrument, NMR spectra were measured on a Bruker ANANCE Ⅲ (500 MHz) spectrometer, and Mass spectra were determined on Thermo-ITQ 1100 mass spectrometer.Ketones, (diacetoxyiodo)benzene and phosphate are commercially available.

A Typical Procedure for α-Phosphoryloxylation of Ketones
A mixture of acetophenone (1a) (0. (1 mL) were added.After separation, the water layer was extracted with CH 2 Cl 2 (2 × 5 mL).The combined organic layer was dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure to give the residue with which the yield of α-phosphoryloxyl acetophenone (3a) was determined in 80% by 1 H NMR technique.The residue was purified on a silica gel plate using (4:1 hexane-ethyl acetate) as eluant to give 3a in the yield of 48%.

Table 2 .
The result of the α-phosphoryloxylation of ketone.