Synthesis and characterization of novel polyvalent organoiodine compounds

Synthesis and characterization of soluble analogues of iodosylbenzene PhIO and (tosyliminoiodo)benzene PhINTs are reported. The syntheses of 4-trifluoromethyl-2-(tertbutylsulfonyl)iodosylbenzene (3) and 4-trifluoromethyl-2-(tert-butylsulfonyl)(tosylimino)iodobenzene (4) increase the repertoire of available soluble organoiodine(III) based oxoand nitrene precursors. We also report the synthesis of a new organoiodine(V) compound, 4-trifluoromethyl-2-(tert-butylsulfonyl)iodylbenzene.


Introduction
Polyvalent organoiodine compounds have found wide synthetic applications in many organic transformations. 1 In particular, tosyliminoiodobenzene (PhINTs) and iodosylbenzene (PhIO) have found favor as primary oxidants in metal-catalyzed aziridinations and epoxidations of various olefins. 2However, the insoluble nature of these reagents, and hence the heterogeneous conditions involving them, hinder efforts to ascertain the reaction mechanism and improve efficiency.The insoluble nature of organoiodine(III) compounds of type ArIX 2 (where X = NTs, O or Cl 2 ) stems in large part from polymeric networks of I•X secondary bonding in the solid state. 3Recent efforts in our group have been focussed on the solubilization of these important compounds by the modification of secondary bonding interactions. 4he characteristic I•O secondary bonding in polyvalent iodine compounds have been utilized to direct self-assembly of organoiodine(III) molecules into chiral and optically pure hypervalent iodine macromolecules and to promote asymmetric oxytosylation reactions. 5During the course of our study of secondary bonding interactions in organoiodine(III) compounds, soluble analogues of PhIO and PhINTs were realized in the synthesis of iodosylarene 1 and (tosyliminoiodo)arene 2, by placing an appropriate substituent in the ortho position of the phenyl ring. 6 Figure 1 Isolation of primary nitrene sources such as 2 and other ArINSO 2 Ar' typically require the electron withdrawing and stabilizing effects of a sulfonyl group.Compound 2 is thus closely related to the well known related carbene source phenyliodonium bis(phenylsulfonyl)methylide PhI=C(SO 2 Ph) 2 first reported by Varvoglis and coworkers. 7Compounds 1 and 2 were found to be effective in metal catalyzed oxidations; however, the epoxidation reactions involving iodosylarene 1 were plagued by the competing disproportionation of 1 to the corresponding iodoarene (I(I)) and iodylarene (I(V)) (equation 1).Iodosylbenzene has been reported to undergo ready disproportionation catalyzed by metal porphyrin or upon heating. 8The outcome of metal catalyzed epoxidation reactions might be improved by stabilizing soluble iodosylarene 1 toward disproportionation.

ArIO
ArI + ArIO 2 Electron-withdrawing substituents on the ring have been reported to enhance the stability of organoiodine(III) compounds such as ArICl 2 , in solution.For instance, a solution of PhICl 2 in CCl 4 loses its oxidizing power at the rate of 0.5% per day at 20 o C.Under similar conditions, p-FC 6 H 4 ICl 2 is reduced only at the rate of 0.04% per day. 9Derivatives of polyvalent iodine compounds with an alkyl substituent at iodine, such as perfluoroalkyliodosyl derivatives, have shown significant stabilization upon introduction of an electron-withdrawing substituent in the alkyl moiety. 10It can be reasoned that reducing the electron density around the iodine atom can stabilize iodosylarene 1 and reduce its tendency towards disproportionation.With the aim of further stabilization of soluble organoiodine(III) species, iodosylarene 3 and (tosyliminoiodo)arene 4, possessing the electron withdrawing trifluoromethyl group were prepared and characterized.

Results and Discussion
Iodanes 3 and 4 were obtained in moderate to good yields by following the synthetic steps outlined in Scheme 1.The unsymmetrically substituted thioether 5 was synthesized from commercially available 3-(trifluoromethyl)bromobenzene by metal-halogen exchange using t-BuLi followed by reaction of t-butyl disulfide Compound 5 was readily oxidized to sulfone 6 in good yield. 11The Snieckus method for directed ortho-lithiation of sulfones was adapted for the synthesis of iodoarene 7. 12 Two geometric isomers of this iodoarene (7a and 7b in a 4:1 ratio) were obtained, and the desired 7a was isolated by recrystallization of the mixture of isomers from diethyl ether.

Scheme 1
Diacetoxyiodoarene 8 obtained by the action of peracetic acid on 7a was used as such, without purification, to synthesize the yellow iodosylarene 3 and pale yellow (tosyliminoiodo)arene 4 in moderate yields (55-65%).Iodanes 3 and 4 were characterized by spectroscopic data and elemental analysis.Like the parent soluble iodanes 1 and 2, these novel iodanes were also found to be soluble in organic media.A 0.30 M solution of iodosylarene 3 (which is a ~4-fold increase over the solubility of 1), and a 0.05 M solution of tosyliminoiodoarene 4 could be prepared in chloroform.
Iodosylarene 3 was evaluated to be only slightly more stable to disproportionation, however, with respect to iodosylarene 1 (69% of 3 in CDCl 3 underwent disproportionation compared to 81% of 1 within the same period of time).The product of this diproportionation, 4trifluoromethyl-2-(tert-butylsulfonyl)iodylbenzene ( 9), was independently synthesized as a white solid by the oxidation of 7a with aqueous sodium hypochlorate (commercial bleach).Compound 9 was characterized by 1 H NMR data and elemental analysis.Consistent with its precipitation during disproprortionation of 3, iodylarene 9 was found to be insoluble in most organic solvents, except DMSO, which was used to record its solution NMR spectrum.
Preliminary investigations on the reactivity of 3 and 4 indicated these novel iodanes to be competent oxidants.For example, styrene oxide was obtained in 15% yield upon epoxidation using 3 under Mn(Salen)Cl catalysis.The relatively low yields are indicative of the competitive catalytic disproportionation of iodosylarene 3 by the manganese catalyst (Scheme 2).Consistent with this proposal, mixtures of 9, styrene, and the manganese catalyst produced no epoxide.However, iodylarene 9 does quantitatively oxidize methyl phenyl sulfide to methyl phenyl sulfoxide.

Conclusions
In summary, the synthesis and characterization of further soluble analogues of PhINTs and PhIO are reported.The new iodanes contain an electron-withdrawing substitute in iodoarene residue and were assessed to be moderately effective oxidants, but the iodosyl derivative still underwent rather facile disproportionation.Introduction of even stronger electron-withdrawing moiety in the design of these organoiodine(III) compounds might have a greater impact upon the stability of iodosylarenes for use as primary oxo-and nitrene precursors in catalytic atom and group transfer.

Experimental Section
General Procedures.Alkyllithium reagents were purchased from Aldrich and titrated with diphenylacetic acid prior to use.Reactions involving the manipulation of air and water sensitive reagents were performed under a nitrogen atmosphere using Schlenk techniques.THF was distilled from sodium benzophenone ketyl.CH 2 Cl 2 and CH 3 CN were distilled from calcium hydride. 1 H and 13 C { 1 H} NMR spectra were recorded on Varian XL200 or Varian XL 300 spectrometers. 19F{ 1 H} NMR spectra were recorded on Varian XL 300 spectrometer.Chemical shifts were referenced internally to residual solvent signals ( 1 H) or externally by using TFA ( 19 F).HR-MS spectra were recorded on a Carlo-Erba Mass Spectrometer.GC-MS spectra were recorded on a HP5890 Series II Gas Chromatograph equipped with a HP 5972 Mass Selective Detector.Elemental analyses were performed by Qualitative Technologies Inc.(QTI), Whitehouse, NJ.

3-(Trifluoromethylphenyl) tert-butyl sulfone (6).
To thioether 6.5 g of 5 (28 mmol) was added 30% H 2 O 2 (20 mL) and glacial acetic acid (20 mL), and the mixture stirred at 85 o C for 4 h to obtain a white precipitate.This solid was isolated by filtration and washed with water until the washings showed no trace of acid by pH paper.The solid was recrystallised from MeOH, and dried in vacuo to obtain 6 as a colorless crystalline solid.Yield: 6.10 g (82%).Mp = 63 o C. 1

4-Trifluoromethyl-2-(tert-butylsulfonyl)iodosylbenzene (3).
Acetic anhydride (2.4 mL) and 30% H 2 O 2 (0.6 mL) was stirred at 42 o C for 5 h.Iodoarene 7a (0.78 g, 2.0 mmol) was added to the resulting solution and the reaction mixture stirred at 30 o C for 24 h to result in a pale yellow solution.The progress of the reaction was monitored by TLC (benzene/silica gel plate) to ensure complete oxidation of 7a.The solvents were removed in vacuo, and the white solid obtained was treated with aqueous 3N NaOH (10 mL) at 0 o C, to obtain a yellow precipitate.The reaction mixture was stirred at 0 o C for 1 h and at room temperature for 1 h.The yellow solid was isolated by filtration, washed with water and diethyl ether to obtain 3. Yield: 0.52 g (64%). 1 4).Acetic anhydride (1.2 mL) and 30% H 2 O 2 (0.3 mL) were stirred at 42 o C for 5 h.Iodoarene 7a (0.40 g, 1.0 mmol) was added to the resulting solution and the reaction mixture stirred at 30 o C for 24 h to afford a pale yellow solution.The progress of the reaction was monitored by TLC (benzene/silica gel plate) to ensure complete oxidation of 7a.The solvents were removed in vacuo, and the white solid obtained was treated with an ice-chilled solution of KOH (0.20 g, 3.5 mmol) and paratoluenesulfonamide (0.17 g, 1.0 mmol) in methanol (5 mL).The resulting pale yellow solution was stirred for 1 h at 0 o C and for 1 h at room temperature.Crushed ice was added to the reaction mixture to obtain a yellow precipitate.This solid was isolated by filtration, washed with water and diethyl ether and dried in vacuo to obtain 4. Yield: 0.30 g (55%). 1