Vanadyl Trichloride

VOCl3

[7727-18-6]  · Cl3OV  · Vanadyl Trichloride  · (MW 173.29)

(oxidative decarboxylation; phenolic coupling)

Alternate Names: trichlorooxovanadium; vanadium oxytrichloride.

Physical Data: mp 77 °C; bp 126-127 °C; d 1.840 g cm-3.

Solubility: sol ether, dichloromethane, benzene.

Form Supplied in: commercially available as a yellow liquid from a number of vendors.

Preparative Methods: by the action of dry Cl2 on vanadium(III) oxide or vanadium(V) oxide.1

Handling, Storage, and Precautions: decomposes in the presence of moisture into vanadic acid and HCl.

Oxidative Decarboxylation-Deoxygenation.

Stoichiometric amounts of VOCl3 can be utilized in the oxidative decarboxylation-deoxygenation of 3-hydroxycarboxylic acids to tri- and tetrasubstituted alkenes,2 enabling direct conversion from the products of classical aldol condensations (eq 1). In some cases, byproducts resulting from dehydration, C-C bond cleavage, double-bond migration, and (E/Z) bond isomerization have been noted, although the latter three problems can be suppressed by the addition of 1,8-Bis(dimethylamino)naphthalene (Proton Sponge). Trichloro(arylimino)vanadium(V), prepared from VOCl3 and the appropriate aryl isocyanate,2,3 can generate higher yields of alkene, free of byproducts, when used as an alternative reagent.

Diphenolic Oxidative Coupling.

There are a number of examples of diphenolic oxidative coupling reactions using VOCl3 as the oxidizing agent. Intermolecular coupling of 1- and 2-naphthol generates 4,4-dihydroxybinaphthyl (eq 2) and 2,2-dihydroxybinaphthyl in 56% and 65% yield, respectively.4 Evidence indicates that intermediate vanadium phenoxides are formed in the process. Under identical conditions, m-cresol yields a mixture of polymeric products. The more reactive Vanadium(IV) Chloride can be used to effect the same transformations and to some degree it complements the use of VOCl3.4

When treated with a stoichiometric amount of trichlorooxovanadium, Cbz-protected tyrosine affords the dityrosine derivative in 20% yield (eq 3).5 A similar reaction with vanadium trifluoride doubles the yield of the desired ortho-ortho coupled product and is preferred due to superior functional group compatibility.

Intramolecular oxidative coupling of phenols, a key step in the biosynthesis of alkaloids and other natural products, can be effected nonenzymatically via this reagent. Although yields are high in simple systems, results are more variable in systems of increased complexity. For example, addition of an ethereal solution of 1,3-bis(hydroxyphenyl)propane to 2.5 equiv of vanadyl trichloride in ether affords the phenolic dienone in 76% yield (eq 4).6 Initial reaction at -78 °C generates the bis(dichlorovanadate) ester which ultimately undergoes oxidative coupling at higher temperature. One-electron oxidants such as Potassium Ferricyanide, Iron(III) Chloride, Manganese Dioxide, and Silver(I) Oxide afford low yields of coupled product due to competing polymerization reactions.7 In a related but more complex example, vanadyl trichloride is utilized in a key coupling step (eq 5) in the total synthesis of (±)-maritidine.8 Here the bis(hydroxyphenyl) compound is converted to the para-para coupled dienone in 24% isolated yield.

This reagent has been utilized in the intramolecular oxidative coupling of a number of benzyltetrahydroisoquinolines,9 as exemplified by the conversion of cis-3,N-bis(methoxycarbonyl)-N-norreticuline to the corresponding isoboldine analog (eq 6).10 Since four regioisomers are possible, (para-para/para-ortho morphinanes and ortho-para/ortho-ortho aporphines), directing the regiochemical outcome can be difficult. It appears that VOCl3 often generates predominantly aporphine products. The effects of steric interactions have been investigated.11 (Diacetoxyiodo)benzene and Thallium(III) Trifluoroacetate have also been utilized to effect the same transformation with less success with regard to yields and regioisomeric ratios.9a,10

Although Vanadyl Trifluoride is often the reagent of choice,12 intramolecular coupling of monophenols has been effected in near quantitative yield with VOCl3 in dichloromethane at -78 °C (eq 7).7,13 On the other hand, oxidative coupling of the nonphenolic substrate (R = Me) leads primarily to the dienone (via alkyl-oxygen cleavage) and a minor component (18%) resulting from coupling and subsequent rearrangement. It has been suggested that, in either case, two successive one-electron oxidations occur with coupling at the cation radical stage.13 Trialkylamines completely inhibit this reaction. Alternative reagents such as silver bis(trifluoroacetate), thallium tris(trifluoroacetate), and vanadium oxytrifluoride14 also induce nonphenolic coupling.


1. Oppermann, Z. Anorg. Allg. Chem. 1967, 351, 113.
2. (a) Meier, I. K.; Schwartz, J. JOC 1990, 55, 5619. (b) Meier, I. K.; Schwartz, J. JACS 1989, 111, 3069.
3. Devore, D. D.; Lichtenhan, J. D.; Takusagawa, F.; Maatta, E. A. JACS 1987, 109, 7408.
4. Carrick, W. L.; Karapinka, G. L.; Kwiatkowski, G. T. JOC 1969, 34, 2388.
5. Brown, A. G.; Edwards, P. D. TL 1990, 31, 6581.
6. Schwartz, M. A.; Holton, R. A.; Scott, S. W. JACS 1969, 91, 2800.
7. Schwartz, M. A.; Rose, B. F.; Holton, R. A.; Scott, S. W.; Vishnuvajjala, B. JACS 1977, 99, 2571.
8. Schwartz, M. A.; Holton, R. A. JACS 1970, 92, 1090.
9. (a) Burnett, D. A.; Hart, D. J. JOC 1987, 52, 5662. (b) Schwartz, M. A. SC 1973, 3, 33. (c) Marino, J. P.; Samanen, J. M. TL 1973, 4553. (d) Franck, B.; Teetz, V. AG(E) 1971, 10, 411.
10. Schwartz, M. A.; Pham, P. T. K. JOC 1988, 53, 2318.
11. (a) McDonald, D.; Suksamrarn, A. TL 1975, 4421. (b) McDonald, D.; Suksamrarn, A. JCS(P1) 1978, 440.
12. Schwartz, M. A.; Rose, B. F.; Vishnuvajjala, B. JACS 1973, 95, 612.
13. Schwartz, M. A.; Hudec, T. T. SC 1986, 16, 1599.
14. (a) Damon, R. E.; Schlessinger, R. H.; Blount, J. F. JOC 1976, 41, 3772. (b) Kende; A. S.; Liebeskind, L. S. JACS 1976, 98, 267. (c) Comins, D. L.; Morgan, L. A. TL 1991, 32, 5919.

Michael K. O'Brien & Benoit Vanasse

Rhône-Poulenc Rorer Pharmaceuticals, Collegeville, PA, USA



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