Benzyl Isopropenyl Ether

[32783-20-3]  · C10H12O  · Benzyl Isopropenyl Ether  · (MW 148.20)

(protecting group for compounds with multiple hydroxy groups;1 acetone enolate equivalent2)

Physical Data: bp 191-192 °C.3

Solubility: sol acetone, benzene.

Preparative Methods: the first reported synthesis of the reagent was accomplished by the pyrolytic decarboxylation of b-benzyloxycrotonic acid.3 An alternate method for the preparation proceeds via dehydrohalogenation of 2-benzyloxy-1-chloropropane with potassium t-butoxide in DMSO (82% yield).1

Alcohol Protection.

Benzyl isopropenyl ether (1) has been shown to react with free hydroxy groups at rt in benzene in the presence of 10 mol % Dichloro(1,5-cyclooctadiene)palladium(II) to produce the corresponding mixed benzyl acetals in 85-98% isolated yield (eq 1).1 The protecting group can also be introduced in comparable yields with catalytic Phosphorus Oxychloride or p-Toluenesulfonic Acid. Cleavage of the mixed acetal took place at rt in the presence of catalytic 5% Palladium on Carbon under 1 atm of hydrogen in 92-99% yield. The protecting group was stable to hydride reducing agents (LAH, DIBAL), alkyllithium, and Grignard reagents, and was stable to alkaline hydrolysis conditions (1 M NaOH/THF, 1/1). Exposure to 1 M Acetic Acid in THF (1/1) effects cleavage of the protecting group.

The primary advantage of this alcohol-protecting group over many similar reagents4 is the neutral conditions used for its introduction and removal. An alternative method for protecting alcohols as mixed acetals makes use of catalytic Cobalt(II) Chloride in MeCN at rt.5 The reported range of yields for this method was slightly lower (68-91%); however, the ready availability and low cost of the cobalt catalyst recommends its use.

A closely related reagent for alcohol protection is 2-phenoxypropene, which was easily prepared from phenyl acetate and Tebbe's reagent in 57% yield.6 Conversion of alcohols to the corresponding phenyl mixed acetals took place with catalytic phosphorus trichloride. Hydrolytic cleavage with 0.1 M HCl and ether was complete in 30 s.

Acetone Enolate Equivalent.

An early application in which (1) was used as an acetone enolate equivalent in a Lewis acid-catalyzed condensation with ketones has been reported.2 For example (eq 2), condensation of (1) with acetone in the presence of Boron Trifluoride Etherate produced 4-benzyloxy-4-methyl-2-pentanone in 52% yield. This early methodology has largely been eclipsed by advances involving the use of silyl enol ethers.

1. Mukaiyama, T.; Ohshima, M.; Murakami, M. CL 1984, 265.
2. Albaiges, J.; Camps, F.; Castells, J.; Fernandez, J.; Guerrero, A. S 1972, 378.
3. Autenrieth, W. CB 1896, 29, 1639.
4. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991; pp 10-68.
5. Iqbal, J.; Srivastava, R. R.; Gupta, K. B.; Khan, M. A. SC 1989, 19, 901.
6. Zandbergen, P.; Willems, H. M. G.; van der Marel, G. A.; Brussee, J.; van der Gen, A. SC 1992, 22, 2781.

Marcus A. Tius

University of Hawaii, Honolulu, HI, USA

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