Potassium t-Butoxide-Benzophenone


[865-47-4]  · C4H9KO  · Potassium t-Butoxide-Benzophenone  · (MW 112.23) (Ph2CO)

[119-61-9]  · C13H10O  · Potassium t-Butoxide-Benzophenone  · (MW 182.23)

(Oppenauer-type oxidations of amino alcohols1)

Physical Data: Ph2CO: mp 49-51 °C; bp 158 °C/10 mmHg. For t-BuOK, see Potassium t-Butoxide.

Solubility: Ph2CO: nonpolar organic solvents; insol H2O.

Form Supplied in: Ph2CO: white crystalline solid; widely available commercially.

Preparative Methods: in situ, usually in a ca. 1:3 molar ratio of the base to the ketone.

Purification: commercially available benzophenone is normally of sufficient purity to be used directly; if further purification is needed, it should be recrystallized from a nonpolar solvent such as cyclohexane and sublimed.2

Handling, Storage, and Precautions: Ph2CO: irritant; avoid contact with the eyes, skin, and clothing; use in a fume hood.

Oppenauer-Woodward Oxidation.

The Oppenauer oxidation of alcohols is usually carried out with Aluminum Isopropoxide and a ketone.3 However, since the aluminum alkoxide complexes with amino groups, this procedure is not useful for oxidizing amino alcohols to amino aldehydes or ketones. This difficulty has been overcome by the use of a procedure often called the Oppenauer-Woodward oxidation, which employs t-BuOK as the base to generate the alkoxide anion of the alcohol and Ph2CO as the hydride acceptor.1 The hydroxy groups of alkaloids are oxidized by the reagent; for example, quinine is oxidized to quininone (eq 1)1a and various morphine derivatives are oxidized to the corresponding ketones in good to excellent yields.1b,c

Oppenauer-Woodward oxidations are normally conducted in refluxing benzene. If the more reactive hydride acceptor fluorenone is substituted for Ph2CO, oxidations can be accomplished at rt,4 although extended reaction times may be required.4b The oxidation of a 4-hydroxypiperidine derivative to the corresponding 4-ketopiperidine, as shown in eq 2, provides an example of this modification.4c t-BuOK/fluorenone is also useful for the oxidation of nonnitrogenous alcohols.4a,5 For example, the less-hindered hydroxy group of a proanthocyanidine derivative is preferentially oxidized by the reagent (eq 3).5

The allylic anion produced upon reaction of the Cr(CO)3 complex of p-allylanisole with t-BuOK in THF undergoes addition followed by in situ oxidation when treated with excess PhCHO (eq 4).6 Benzaldehyde and other aldehydes have been used as hydride acceptors in a modification of the Oppenauer oxidation which utilizes magnesium alkoxides as hydride donors.7

Tandem Oppenauer-Woodward oxidations-aldol condensations can be performed with appropriate substrates. Eqs 5 and 6 provide examples of the use of these reactions in connection with the total synthesis of lycopodine8 and elaeocarpine9 alkaloids, respectively.

1. (a) Woodward, R. B.; Wendler, N. E.; Brutschy, F. J. JACS 1945, 67, 1425. (b) Rapoport, H.; Naumann, R.; Bissell, E. R.; Bonner, R. M. JOC 1950, 15, 1103. (c) Gates, M.; Tschudi, G. JACS 1956, 78, 1380.
2. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1992; p 94.
3. Djerassi, C. OR 1951, 6, 207.
4. (a) Warnhoff, E. W.; Reynolds-Warnhoff, P. JOC 1963, 28, 1431. (b) Wommack. J. B., Jr.; Pearson, D. E. JMC 1970, 13, 383. (c) Vincent, S. H.; Shambhu, M. B.; Digenis, G. A. JMC 1980, 23, 75.
5. Nonaka, G.-I; Morimoto, S.; Kinjo, J.; Toshihiro, T.; Nishioka, I. CPB 1987, 35, 149.
6. Gentric, D.; LeBihan, J.-Y.; Senechal-Tocquer, M.-C.; Senechal, D.; Caro, B. TL 1986, 27, 3849.
7. Byrne, B.; Karras, M. TL 1987, 28, 769.
8. Heathcock, C. H.; Kleinman, E. F.; Binkley, E. S. JACS 1982, 104, 1054.
9. Tufariello, J. J.; Ali, S. A. JACS 1979, 101, 7114.

Drury Caine

The University of Alabama, Tuscaloosa, AL, USA

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