4-Methoxybenzyl 2,2,2-Trichloroacetimidate1

[89238-99-3]  · C10H10Cl3NO2  · 4-Methoxybenzyl 2,2,2-Trichloroacetimidate  · (MW 282.56)

(reagent for the protection of alcohols under mildly acid conditions)

Physical Data: bp 135-137 °C; d 1.361 g cm-3.

Solubility: sol most organic solvents.

Form Supplied in: clear liquid.

4-Methoxybenzyl 2,2,2-trichloroacetimidate is used to protect alcohols as the p-methoxybenzyl ether. It was first used in oligoribonucleotide synthesis2 and the utility and generality of the method was extended by Yonemitsu.3 The main advantage of using this reagent is that it provides an alternative to the Williamson ether synthesis, which is commonly used to introduce this protective group under basic conditions. Since this reagent is used to install the group under acidic conditions, it provides a method to protect base-sensitive alcohols. Protic acids such as Trifluoromethanesulfonic Acid, 10-Camphorsulfonic Acid,5 and p-Toluenesulfonic Acid6 generally give excellent yields of product. Boron Trifluoride Etherate7 and Triphenylmethyl Perchlorate are also effective catalysts. The preferred solvents are ether and CH2Cl2, but hydrocarbon cosolvents have been used.2,7,8 Tertiary, secondary, and primary alcohols are protected with equal efficiency, but the question of selectivity has not been addressed. The reagent can be used to install the p-methoxybenzyl ether group in the presence of a variety of other protective groups, the most notable of which is the the t-butyl group considering the strong acids used as catalysts.4 Table 1 shows some of the structural types that have been protected with this reagent. Many of these examples serve to illustrate cases where basic conditions could not be used to achieve protection. For a discussion of the deprotection of the MPM group, see p-Methoxybenzyl Chloride.

Related Reagents.

Benzyl Bromide; Benzyl Chloride; Benzyl Iodide; 3,4-Dimethoxybenzyl Bromide; p-Methoxybenzyl Chloride; (p-Methoxybenzyloxy)methyl Chloride.

1. For a review of protective groups, see: Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991.
2. Takaku, H.; Uedo, S.; Ito, T. TL 1983, 24, 5363.
3. Nakajima, N.; Horita, K.; Abe, R.; Yonemitsu, O. TL 1988, 29, 4139.
4. Kim, S.; Salomon, R. G. TL 1989, 30, 6279.
5. Walkup, R. D.; Kane, R. R.; Boatman, P. D.; Cunningham, R. T. TL 1990, 31, 7587.
6. Adams, E.; Hiegemann, M.; Duddeck, H.; Welzel, P. TL 1990, 46, 5975.
7. Hebert, N.; Beck, A.; Lennox, R. B.; Just, G. JOC 1992, 57, 1777.
8. Audia, J. E.; Boisvert, L.; Patten A. D.; Villalobos, A.; Danishefsky, S. J. JOC 1989, 54, 3738.

Peter G. M. Wuts

The Upjohn Co., Kalamazoo, MI, USA

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