Diphenylselenium Bis(trifluoroacetate)

[42572-21-4]  · C16H10F6O4Se  · Diphenylselenium Bis(trifluoroacetate)  · (MW 459.22)

(two-electron oxidant for phenolic compounds and amines under nonaqueous conditions; source of diphenylselenonium cations in reactions with certain phenols)

Physical Data: mp 175-176 °C.

Solubility: very sol dimethoxyethane, methylene chloride; reacts with protic or nucleophilic solvents.

Form Supplied in: colorless solid; not commercially available.

Analysis of Reagent Purity: mp, IR, and elemental analysis.

Preparative Method: predried diphenyl selenoxide (0.001 mol) is dissolved in 10 mL of dry dimethoxyethane and 0.15 mL (0.001 mol) of freshly distilled Trifluoroacetic Anhydride is added by syringe. After the reaction mixture has been stirred for 15 min at 0 °C, the solvent is removed in vacuo to give a white solid (eq 1).1

Handling, Storage, and Precautions: thermally stable, but very hygroscopic. While the reagent may be isolated in an inert atmosphere, it is most conveniently used by generating it in situ. This reagent should be handled in a fume hood.

Structure and Properties of the Reagent.

By analogy to other tetrasubstituted sulfuranes and selenuranes,2 the diphenylselenium bis(trifluoroacetate) reagent is believed to exist in a trigonal bipyramidal geometry in which the trifluoroacetoxy groups assume the apical positions.3 The covalent and symmetrical selenurane structure is confirmed by the normal IR absorption for the acyl groups (1738, 1718 cm-1) and the singlet 19F NMR absorption at 2.0 ppm downfield from an external trifluoroacetic acid standard. While the reagent is highly hygroscopic, it can easily be handled to obtain an elemental analysis.

Oxidations of Phenolic Compounds.

The title reagent serves as a mild two-electron oxidant for phenols and catechols. The presence of the two trifluoroacetates as leaving groups in the reagent provide a facile exchange mechanism for the incorporation of nucleophiles. There are three modes of oxidation observed for phenols with this reagent: phenolic coupling, benzylic oxidation, and hydroxylation. Some of the prime advantages of this reagent over the more traditional metal oxidants for oxidations of phenols include the homogeneous nature of the reagent in organic solvents, the stoichiometric control of oxidation, and the selectivity found for the oxidation sites. As a typical oxidation process for phenols, 2,6-dimethylphenol undergoes a clean para-para oxidative coupling with subsequent oxidation of the hydroquinone with 2 equiv of the reagent at rt (eq 2).1

The coupling reaction (eq 2) occurs exclusively when the oxidizing reagent is added to the phenol. In contrast, when the phenol is added to a solution of the oxidant at rt, the major oxidation pathway involves para-hydroxylation and subsequent oxidation to yield 2,6-dimethylbenzoquinone (eq 3). This process involves a unique nucleophilic addition of trifluoroacetate to an aromatic ring.

The mechanistic interpretation of these reactions involves the initial ligand exchange of a trifluoroacetate for the phenol. The newly formed aryloxyselenurane is an activated aromatic ring susceptible to nucleophilic attack either by another phenol (eq 2) or the trifluoroacetate anion (eq 3). The latter process is accentuated by an increase of the p-benzoquinone product when additional lithium trifluoroacetate is added to the reaction solution (eq 4).1

Other phenols that undergo the para-oxidation to form benzoquinones include thymol (eq 5) and 3,5-dimethylphenol (eq 6).

Intramolecular phenolic coupling reactions are also possible with the title reagent. At low temperatures the diphenolic compound in eq 7 undergoes oxidative coupling to produce the spirodienone product.

Applications of the diphenylselenium bis(trifluoroacetate) reagent to the synthesis of tetrahydrobenzylisoquinoline alkaloids have revealed some very selective and clean benzylic oxidative processes. In the tetrahydroisoquinoline system of eq 8, the benzylic carbon para to the free phenol is initially oxidized to the para-quinone methide which rapidly isomerizes to the dihydroisoquinoline system.1

Oxidations of Heterocyclic Amines.

The diphenylselenium bis(trifluoroacetate) reagent is a powerful two-electron oxidant for primary, secondary, and tertiary amines. In the tetrahydroisoquinoline system, the major oxidation products are the imines (eq 9).4 In some cases (R = Me), a minor reaction product is the fully oxidized quinoline (10%). Thus the controlled oxidation of a secondary amine to an imine can be effected under very mild conditions.5 When tertiary amines are oxidized with the reagent, regiospecific iminium ions are formed under nonaqueous conditions. Workup of this reaction with cyanide salts gives rise to the well-known Reissert compounds (eq 10).4

Transfer of Diphenylselenonium Cations.

In systems where phenolic coupling, benzylic oxidation, or hydroxylation processes are restricted, reactions of the reagent with certain phenols yield selenonium phenoxides or rearrangement products. For example, estrone is converted to its ortho-diphenylselenonium zwitterion with 1 equiv of the reagent (eq 11).1

A similar ortho-selenonium phenoxide was observed in the reaction of the trisubstituted phenol shown in eq 12, accompanied by an unusual rearrangement product of the zwitterion.6 The phenoxide zwitterion is a precursor to the diaryl ether.

1. Schwartz, A. Ph.D. Thesis, University of Michigan, 1978.
2. The title reagent was first reported by Paetzold, but there was no characterization of the compound: Horn, V.; Paetzold, R. Z. Anorg. Allg. Chem. 1973, 398, 186.
3. Livant, P.; Martin, J. C. JACS 1977, 99, 5761.
4. Marino, J. P.; Larsen, R. D., Jr. JACS 1981, 103, 4642.
5. Larsen, R. D., Jr. Ph.D. Thesis, University of Michigan, 1982.
6. Marino, J. P.; Dax, S. TL 1987, 28, 4007.

Joseph P. Marino & David P. Holub

University of Michigan, Ann Arbor, MI, USA

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