Iodosylbenzene1

(PhIO)n

[536-80-1]  · C6H5IO  · Iodosylbenzene  · (MW 220.01)

(oxygen atom transfer to ketones,4 metal-catalyzed oxygen atom transfer to alkenes,7-13 formation of a-diketones,14 bridgehead triflates,16 a,b-unsaturated lactones and ketones,19 a-hydroxymethyl acetals,20 a-keto triflates,17 a-hydroxy ketones,18 C-C coupling,22-24 oxidation of amines,25,26 azidation22-30)

Alternate Name: iodosobenzene.

Physical Data: mp 210 °C with decomposition (explodes); polymeric.

Solubility: slightly sol H2O, MeOH. In MeOH the reagent is PhI(OMe)2. Both solvents, as well as CH2Cl2 and MeCN, are used for reactions.

Form Supplied in: white to slightly yellow solid from synthesis.2,3

Preparative Method: prepared as a white solid by base hydrolysis of commercially available (Diacetoxyiodo)benzene in 75% yield.2

Purification: washing the solid with CHCl3 to remove traces of PhI. The material is obtained in about 99% purity as determined iodometrically.3

Handling, Storage, and Precautions: indefinitely stable; refrigeration should be used for long-term storage.

Oxygen Atom Transfer from PhIO: a-Lactones from Ketenes (Uncatalyzed Epoxidation).

Ketenes react with PhIO to yield an intermediary a-lactone which undergoes polymerization to a polyester in yields ranging from 63 to 90% (eq 1).4 Likewise, tetracyanoethylene forms tetracyanoethylene oxide in 74% yield upon reaction with PhIO.4 a-Lactones have also been prepared by the ozonation of ketenes5 and via the addition of triplet dioxygen to ketenes.6

Metal-Catalyzed Oxygen Transfer: Epoxide Formation.

Iron(III) and manganese(III) porphyrins catalyze oxygen transfer from PhIO to aromatic substrates to yield phenolic products, probably via arene oxides.7 Alkene epoxidation can also be achieved using this system. Simpler ligands such as Schiff's bases,8 amides,9 phosphines,10 and salts of heteropolyaromatics11 have been used. Bleomycin complexes of iron, copper, and zinc also cause oxidation of alkenes.12 Noteworthy is the epoxidation of cyclohexene (eq 2).13 These systems are of theoretical interest as models for cytochrome P-450 and have not as yet achieved general preparative significance.

Oxidation of Alkynes to a-Diketones.

Ruthenium catalysis is effective in the oxidation of internal (eq 3) and terminal alkynes (eq 4).14 Secondary alcohols are oxidized to ketones in good yield using m-iodosylbenzoic acid and the base-extractable m-iodobenzoic acid can be recycled.15

Activated PhIO using TMSOTf: Oxidative Displacement of Bridgehead Iodine to Yield Bridgehead Triflates.

A series of cubyl triflates was synthesized using PhIO and Trimethylsilyl Trifluoromethanesulfonate (forms the reactive intermediate [PhIOTMS]+ TfO-) (eq 5).16 Cubyl alcohol is unstable and this direct functionalization was critically useful.

Oxidation of Silyl Enol Ethers to a-Keto Triflates with PhIO-TMSOTf.

The oxidation of silyl enol ethers to a-keto triflates is a generally useful reaction (eqs 6 and 7).17

Oxidation of Silyl Enol Ethers with PhIO in H2O-BF3.Et2O to a-Hydroxy Ketones.

A direct route to a-hydroxy ketones is achieved via oxidation of aromatic, heteroaromatic, and aliphatic silyl enol ethers with PhIO in Boron Trifluoride Etherate-H2O (eq 8).18 This is a simple and broadly useful reaction for the a-hydroxylation of ketones.

Oxidation of Lactones to Higher Homologous a,b-Unsaturated Lactones.

Ring expansion of lactones occurs via oxidation of the derived trimethylsilyloxycyclopropanols to give the higher homologous a,b-unsaturated lactones (eq 9).19 Silyl enol ethers behave analogously (eqs 10 and 11).19

Oxidation of Ketones to Form a-Hydroxydimethyl Acetals.

The reagent PhI(OAc)2-KOH-MeOH is equivalent to PhIO-KOH-MeOH; however, PhI(OAc)2 is commercially available whilst PhIO is not. Consequently, the reagent (Diacetoxyiodo)benzene, [PhI(OAc)2], is now used even though the original process was discovered using PhIO/MeOH.20a This reagent has been employed in the synthesis of the steroidal dihydroxyacetone side chain (eq 12).20b

Formation of Carbon-Carbon Bonds: 1,4-Diketones via Coupling Reaction with PhIO/BF3.Et2O.

The addition of BF3.Et2O to PhIO yields an intermediary reagent, [PhI+OBF3-], which is reactive with silyl enol ethers derived from ketones. In the presence of water or an alcohol, a-hydroxylation or a-alkoxylation occurs (eq 13),18 while in the absence of a protic nucleophile self-coupling occurs to yield a 1,4-diketone (eq 14).21

Unsymmetrical coupling occurs via in situ generation of a phenyliodonium intermediate at -78 °C and subsequent introduction of a silyl enol ether as a coupling partner (eq 15).22

Allylation of aromatic compounds takes place when allylmetal (Group 14) compounds react with aromatic compounds and iodosylbenzene in the presence of boron trifluoride etherate (eq 16).23,24

Oxidation of Amines.

Primary amines yield nitriles (eq 17) or ketones (eq 18).25

Cyclic secondary amines yield lactams (eq 19).25 N-Methyl cyclic amines as well as nicotine behave analogously (eq 20).25

Cyclic amino acids such as L-proline, pipecolinic acid, and L-2-pyrrolidinone-5-carboxylic acid undergo oxidative decarboxylation with iodosobenzene in various solvents (including water) to yield the corresponding lactam (eq 21).26

Formation of Azides Using PhIO-NaN3 or PhIO-TMSN3.

Cholesterol is converted to the allylic azide with PhIO-NaN3-MeCO2H, namely 7a-azidocholest-5-en-3b-ol.27 A similar reaction occurs with Pb(OAc)4-TMSCl.28

Formation of b-Azido Ketones using PhIO-TMSN3.

The reaction between Azidotrimethylsilane and PhIO must be carried out at low temperatures. At rt they react violently. Eq 22 shows the b-azido functionalization of triisopropylsilylenol ethers.29

N,N-Dimethylarylamines under these conditions yield N-methyl-N-azidomethyl arylamines (eq 23).30

The thiocarbonyl group of 2-thiouracil is converted to the carbonyl group with PhIO (eq 24).31

Related Reagents.

Iodosylbenzene-Boron Trifluoride; Iodosylbenzene-Dichlorotris(triphenylphosphine)ruthenium.


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Robert M. Moriarty & Jerome W. Kosmeder II

University of Illinois at Chicago, IL, USA



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