CO 2 -activated NaClO-5H 2 O enabled smooth oxygen transfer to iodoarene: a highly practical synthesis of iodosylarene

We wish to dedicate this paper to the memory of Professor Kilian Muñiz, who devoted his life to the development of hypervalent iodine chemistry


Introduction
2][3][4] Among them, iodosylbenzene (1a), which has been known since 1892, offers many advantages.0][11] However, an excess amount of NaOH is required to complete the ligand exchange, and as a result, tedious work-up, including careful rinsing with large amounts of water (in order to remove remaining base), is inevitable. 12This is problematic, because 1a is light-sensitive and gradually decomposes at room temperature. 5,6In contrast, direct oxidation of iodobenzene 4a with dimethyldioxirane 5 is a fascinating alternative approach, as the only waste product is acetone, but it suffers from a low yield of 1a owing to the occurrence of over-oxidation, affording pentavalent iodylbenzene (6a). 13Herein, we report a direct base-free approach for the synthesis of 1 from iodoarene 4, making it possible to use 1a for subsequent transformations in one pot.The key to this approach is the in situ activation of NaClO-5H2O with carbon dioxide (CO2).

Results and Discussion
We recently reported that NaClO-5H2O serves as an excellent oxidant for the synthesis of (diacetoxyiodo)arene 2 in the presence of acetic acid at room temperature. 14We also reported that the oxidation of 2-iodobenzoic acid 7 with NaClO-5H2O, leading to the formation of 2-iodoxybenzoic acid (IBX) 8, is accelerated by gaseous CO2. 15,16Encouraged by these findings, we commenced our study by examining the direct oxidation of iodobenzene (4a) with NaClO-5H2O under a CO2 atmosphere.Exposure of 4a to equimolar NaClO-5H2O in MeCN at room temperature under CO2 (1 atm) resulted in the rapid appearance (within a few minutes) of a canary yellow-colored solution, which subsequently faded.After 10 minutes, 1a was obtained in 75-78% yield as a pale-yellow solid by means of a simple suction filtration-vacuum drying sequence (Table 1, entry 1).The FT-IR analysis of 1a thus obtained showed two strong bands due to the I-O stretching vibration (ν = 525, 446 cm -1 ). 17The purity was confirmed to be ≥98% by iodometric titration.Under these conditions, overoxidized iodylbenzene (6a) was not formed.In the absence of CO2 (under air), 1a was not formed at all (entry 2).The reaction could be readily and safely scaled up to 74 mmol (4a: 15 g) without decrease in the efficiency (entry 4).The use of MeCN was essential for this transformation: the use of either solvent-free conditions or water-immiscible solvents such as toluene, CH2Cl2, and AcOEt was much less effective (entries 5-8).Other polar water-miscible solvents (acetone, DMF, and THF) did not give satisfactory results (entries 9-11). 18urprisingly, conventional 13% and 4% aqueous NaClO solution also served as an effective oxidant, but an excess amount of the reagent led to selective formation of the over-oxidized product PhIO2 6a, instead of 1a (entries 12-14). 14,15In contrast, Ca(ClO)2-3H2O did not work at all in this system, partly because of its poor solubility in MeCN (entry 15).The substitution of CO2 with solid NaHCO3 is potentially attractive in terms of convenience and cost, though the yield of 1a is only moderate (entry 16).The optimized conditions were applicable to not only the electron-deficient iodoarenes 4b-e, but also the electron-rich iodoarenes 4f-h, affording iodosylarenes 1b-h in good to high yields (Table 2).In contrast to 4b, 2-(nitro)iodobenzene 4i selectively afforded pentavalent 2-nitro(iodyl)benzene (6b), probably due to the coordination of neighboring oxygen of the nitro group, which facilitates further oxidation. 19It should be emphasized that the readily hydrolyzable 4-(methoxycarbonyl)iodosylbenzene 1d was selectively obtained in good yield under conventional hydrolysis conditions (Figure 1(A)) without saponification. 20The attempted oxidation of highly electron-deficient pentafluoroiodobenzene (4j) was unsuccessful, in marked contrast to the facile oxidation of 4j in AcOH, yielding C6F5I(OAc)2. 14Other electron-deficient substrates, (nonafluorobutyl iodide (4k) and bromobenzene (4i)), were not oxidized under these conditions.
On the basis of the reported rate acceleration of the disproportionation of NaClO to NaClO3 and NaCl under a CO2 atmosphere, 29 together with our Raman spectroscopic study (Figure S1 in the Supporting Information), we consider that the reaction mechanism most likely involves the initial formation of Cl2O or HOCl as an active species (Scheme 2, Figure S2 in the Supporting Information). 30The intervention of Cl2O was further confirmed by connected flask experiment (Figure S3 in the Supporting Information).The disproportionation products, NaClO2 and NaClO3, did not serve as active oxidants (Scheme S1 in the Supporting Information).In an early stage of the oxidation of iodobenzene (4a) (yellow solution stage), we confirmed the presence of PhICl2 3 and µ-oxo dimer 24 by 1 H NMR and ESI-MS analyses (Figure S4 in the Supporting Information).These results suggest that the first step of the oxidation probably involves the nucleophilic attack of iodobenzene on active Cl + species to give a transient intermediate 23, followed by rapid ligand exchange on the iodine(III) center to give 3 or 24, with the precipitation of polymeric iodosylbenzene (1a).The bands due to I-O stretching vibration of 1a obtained by our method are slightly different from those reported for a sample obtained by NaOH hydrolysis (ν = 490, 445 cm -1 ), 17 which might suggest differences in the polymeric I-O chain length/angle.The difference in reactivity between 1a prepared by our method and by the classical hydrolysis method is consistent with this idea (Scheme S2 in Supporting Information).Similar enhancement of the oxidizing ability of iodosylbenzene oligomer [(PhIO)3SO3] has been reported by Zhdankin and co-workers. 31heme 2. Proposed reaction mechanism.

Conclusions
We have developed an efficient method for the preparation of iodosylarene 1 using NaClO and CO2.Since the method does not require the presence of a base, a variety of subsequent transformations can be performed in one pot.This method should be practically useful in explorations of new areas of organic/organometallic/bioorganic chemistry.Investigations of the reaction mechanism and further applications of NaClO to iodoarene-catalyzed oxidation under CO2 are in progress.

Experimental Section
General.IR spectra were recorded on a JASCO FR/IR-4700 spectrometer.Raman spectra were obtained on a NRS-4500 1 H NMR spectra were recorded on a BRUKER AVANCE III HD 500 spectrometer (TMS, HDO, or CHD2SOCD3 as an internal standard).GCMS: Mass spectra (MS) were obtained on Agilent 7890A/ 5975C or 7890B/5977A spectrometers.Electrospray ionization (ESI) mass spectra were recorded on a Shimadzu LC-MS 2020 spectrometer.Melting points were determined in SRS MPA 100 OptiMelt Automated Melting Point System without correction.Sodium hypochlorite pentahydrate was purchased from Fujifilm Wako Pure Chemical Industries, Co. Ltd.Other materials were purchased from Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich Co., LLC, and Fujifilm Wako Pure Chemical Industries, Co. Ltd.CAUTION: Although we have never encountered any safety-related issues during the synthesis of 1, the product should be stored in a freezer at ≤ -20 °C, since prolonged storage of 1a at room temperature and at 0 °C leads to disproportionation reaction producing a mixture of PhI 4a and potentially explosive PhIO2 6a. 6,32rying under elevated temperature should be avoided, since disproportionation of 1 is known to be accelerated by heating under reduced pressure. 5,33neral procedure for synthesis of PhIO 1a (3 mmol scale).To a stirred suspension of NaClO-5H2O (496 mg, 3.0 mmol) in MeCN (2 mL) was added iodobenzene (4a) (336 µL, 3.0 mmol) under CO2 at room temperature, and the mixture was vigorously stirred for 10 minutes.To the resulting yellow suspension was added a small amount of water to triturate the solid, which was then was collected by suction filtration.The filter cake was washed with water (3 X 5 mL), then acetone or AcOEt (3 X 5 mL).The product was dried at room temperature under reduced pressure (0.3 Torr) for 2 hours to give 1a (495 mg, 75%) as a pale yellow solid.The purity of 1a was determined by iodometric titration to be 98-100%.Iodosylbenzene (1a). 17  NMR (500 MHz, DMSO-d6): δ 8.37 (dd, J = 7.9, 1.2 Hz, 1H), 8.30 (dd, J = 7.9, 1.2 Hz, 1H), 8.19 (ddd, J = 7.9, 7.6, 1.2 Hz), 7.89 (ddd, 7.9, 7.6, 1.2 Hz). 19arge-scale synthesis of 1a.To a stirred suspension of NaClO-5H2O (13.3 g, 80.8 mmol) in MeCN (40 mL) was added iodobenzene (4a) (15.0 g, 74 mmol) under CO2 at room temperature, and the mixture was vigorously stirred for 10 minutes.During the reaction, no distinct exothermic event was observed.To the resulting yellow suspension was added a small amount of water to triturate solid, which was then collected by suction filtration.The filter cake was washed with water (10 X 5 mL) until the pH of the filtrate becomes neutral, followed by washing with AcOEt (10 X 5 mL).The resulting pale-yellow solid was dried at room temperature under reduced pressure (0.3 Torr) for 2 hours to give 1a (12.0 g, 74%) as a pale yellow solid.The purity of 1a was determined by iodometric titration to be 94%.One-pot synthesis of imino-λ 3 -iodane 8. To a stirred suspension of NaClO-5H2O (490 mg, 3.0 mmol) in MeCN (2 mL) was added iodobenzene (4a) (335 µL, 3.0 mmol) under CO2 at room temperature, and the mixture was vigorously stirred for 10 minutes.To the resulting pale-yellow slurry were added 4-nitrobenzenesulfonamide (7) (606 mg, 3.0 mmol) and K2CO3 (1.24 g, 9.0 mmol) at room temperature, and the mixture was stirred for 12 hours.After the addition of water (ca. 5 mL), the solid was collected by suction filtration.The filter cake was washed with water (3 X 5 mL) then acetone (3 X 5 mL) to give imino-λ 3 -iodane 8 (849 mg, 70%) as a white to pale yellow solid.