Vanadyl Trifluoride

VOF3

[13709-31-4]  · F3OV  · Vanadyl Trifluoride  · (MW 123.94)

(phenolic coupling)

Alternate Names: vanadium oxytrifluoride; trifluorooxovanadium.

Physical Data: mp 300 °C.

Solubility: sol TFA, CH2Cl2.

Form Supplied in: commercially available as a white solid.

Introduction.

Vanadyl trifluoride has demonstrated utility in intramolecular phenolic coupling reactions, a transformation of pivotal importance in alkaloid biosynthesis. For example, the benzyltetrahydroisoquinoline (1) has been converted to the oxoaporphine (2) in 59% yield (eq 1).1 Although alternative reagents such as CrO3, MnO2/TFA, and (CF3CO2)3Tl2 have proven less successful in this reaction, MoOCl4/TFA/CHCl3 generates similar yields of oxoaporphine (62%). Trifluoroacetic Acid is an effective medium for these oxidations, particularly with moisture sensitive oxidants.1 Reaction temperatures vary between -78 °C and ambient temperature.

Phenyl Ether Coupling.

Vanadyl trifluoride will promote intramolecular oxidative coupling between nonphenolic aryl ethers, as exemplified in the syntheses of (±)-isostegane,3 (±)-stegamycin,4 and the acyl-neospirinedienones.5 In the total synthesis of (±)-tylophorine (eq 2),6 for instance, the reaction is complete in 1 h at room temperature in 69% yield.

Asymmetric Synthesis.

Several asymmetric syntheses have employed VOF3 as an intramolecular coupling agent. Syntheses of (+)-deoxyschizandrin (eq 3),7 (+)-glaucine, and (+)-homoglaucine8 have all utilized this reagent in the key oxidative coupling step. In the latter two cases, ruthenium tetrakis(trifluoroacetate) is an equally effective oxidant, and there have been claims that this reagent is superior to vanadyl trifluoride.9

Intermolecular oxidative aryl coupling is also promoted by VOF3, as exemplified by the synthesis of symmetrical biaryl analogs of the biphenomycin antibiotics (eq 4).10 Moderate yields are obtained and VOF3 is preferred over other reagents such as Vanadyl Trichloride because of higher yields and superior functional group compatibility. When these authors10 attempted an intramolecular version of this transformation, VOF3 failed to induce the cyclization.

The diaryl chiral oxazolidine (3) (eq 5)11 has been converted to the corresponding spirodienone (4) in near quantitative yield by using VOF3. VOCl3 and Phenyliodine(III) Bis(trifluoroacetate) have also been utilized to effect this transformation, albeit in lower yields. This example constitutes an efficient simulation of the biosynthetic pathway of alkaloids both in terms of yield and stereochemical outcome.

Biomimetic Oxidative Coupling.

Vanadyl trifluoride has been employed successfully in the biomimetic synthesis of the vancomycin12 class of glycopeptides. The array of functionality present in the starting material and the degree of asymmetric induction achieved in the cyclization illustrates the utility of this reagent in complex synthesis. Apparently, the atropdiastereoselection13 is greatly influenced by the various protective groups on the starting tripeptide (particularly since the Boc group is unstable to these reaction conditions), the substituents on the phenyl ring, and probably the resulting A(1,3) strain, although the mechanistic details of this oxidation are unclear (eq 6). Apparently residual chloride in commercial TFA is sequestered by the AgI salts, while Boron Trifluoride Etherate prevents the attack of oxygen nucleophiles on the radical cation and the TFA/TFAA solvent combination12 traps adventitious water. Manganese(III) Acetylacetonate is the only other reagent to effect this transformation, although in lower yield. Reagents such as Tl(TFA)3, FeCl3, VOCl3, CoF3, and the Pt anode failed to induce cyclization.


1. Kuchan, S. M.; Liepa, A. J. JACS 1973, 95, 4062.
2. Schwartz, M. A.; Rose, B. F.; Vishnuvajjala, B. JACS 1973, 95, 612.
3. Damon, R. E.; Schlessinger, R. H.; Blount, J. F. JOC 1976, 41, 3772.
4. Kende, A. S.; Liebeskind, L. S. JACS 1976, 98, 267.
5. Kuchan, S. M.; Kameswaran, V.; Lynn, J. T.; Williams, D. K.; Liepa, A. J. JACS 1975, 97, 5622.
6. Comins, D. L.; Morgan, L. A. TL 1991, 32, 5919.
7. Biftu, T.; Hazra, B. G.; Stevenson, R. CC 1978, 491.
8. Gottlieb, L.; Meyers, A. I. JOC 1990, 55, 5659.
9. Kupchan, S. M.; Dhingra, O. P.; Kim, C. K.; Kameswaran, V. J. JOC 1978, 43, 2521.
10. Brown, A. G.; Edwards, P. D. TL 1990, 31, 6581.
11. White, J. D.; Butlin, R. J.; Hahn, H.-G.; Johnson, A. T. JACS 1990, 112, 8595.
12. Evans, D. A.; Dinsmore, C. J.; Evrard, D. A.; DeVries, K. M. JACS 1993, 115, 6426.
13. Evans, D. A.; Dinsmore, C. J. TL 1993, 34, 6029.

Benoit Vanasse & Michael K. O'Brien

Rhône-Poulenc Rorer Pharmaceuticals, Collegeville, PA, USA



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