Bromomethyl Methyl Ether


[13057-17-5]  · C2H5BrO  · Bromomethyl Methyl Ether  · (MW 124.96)

(alkylating agent; formaldehyde equivalent;1-8 alcohol protecting group9-14)

Alternate Name: BMME.

Physical Data: bp 87 °C; d 1.531 g cm-3.

Form Supplied in: colorless to light yellow liquid.

Handling, Storage, and Precautions: lachrymator, possible carcinogen, handle with care. Extremely destructive to tissue of mucous membranes, eyes, and skin. Wear respirator, chemical-resistant gloves, and safety goggles.

Alkylating Agent.

Bromomethyl methyl ether (BMME) has been used in the preparation of a-methylene ketones1 and lactones.2 Reaction of a silyl enol ether with 1.5 equiv of BMME in the presence of 5 mol% of Tin(II) Bromide leads to good yields of a-methylene ketones after treatment with 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (eq 1). The reaction is thought to proceed via an intermediate stannane complex which is attacked by bromide ion to give an a-bromomethyl ketone. The reaction can be carried out in a one-pot operation, and proceeds in modest to good yields.

In the course of their synthesis of the pseudoguaianolide aromaticin, Lansbury et al. used BMME as a latent formaldehyde equivalent. Alkylation of the functionalized lactone (eq 2) with BMME (Lithium Diisopropylamide, HMPA) was followed by hydrolysis to a hydroxy acid and in situ elimination of the methoxy group. Careful quenching of the reaction was necessary to avoid methanol addition to the newly formed a-methylene lactone.

Williams3 utilized bromomethyl methyl ether in an enantioselective synthesis of 2,6-diamino-6-(hydroxymethyl)pimelic acid (eq 3). The chiral oxazinone was first alkylated with iodobutene followed by subsequent alkylation with bromomethyl methyl ether. The bis-alkyl adduct was then converted to the desired product after a number of steps.

Schank4 studied the alkylation of sulfinate anions (eq 4) with bromomethyl methyl ether. Alkylation occurs predominantly on the sulfinyl oxygen to give an unstable compound along with minor amounts of S-alkylated product. The unstable compound rearranges upon heating to give the product.

Alcohol Protecting Group.

Eqs 5-7 illustrate the use of bromomethyl methyl ether for forming the methoxymethyl ether (MOM) protecting group.9-14 Typically the alcohol is reacted with BMME in the presence of Diisopropylethylamine (DIEA) as an acid scavenger.

1. Hayashi, M.; Mukaiyama, T. CL 1987, 1283.
2. (a) Smith, A. B., III; Dieter, R. K. JACS 1981, 103, 2009. (b) Smith, A. B., III; Dieter, R. K. JACS 1981, 103, 2017.
3. Williams, R. M.; Im, M.-N.; Cao, J. JACS 1991, 113, 6976.
4. Schank, K.; Schmitt, H.-G. CB 1974, 107, 3026.
5. Boncza-Tomaszewski, Z.; Engel, C. R. Steroids 1982, 39, 107.
6. Gorski, R. A.; Wolber, G. J.; Wemple, J. TL 1976, 2577.
7. Syper, L.; Mlochowski, J.; Kloc, K. T 1983, 39, 781.
8. Malm, L.; Summers, L. JACS 1951, 73, 362.
9. Wagner, A.; Heitz, M.-P.; Mioskowski, C. TL 1989, 30, 1971.
10. Nakata, T.; Nagao, S.; Mori, N.; Oishi, T. TL 1985, 26, 6461.
11. Tino, J. A.; Lewis, M. D.; Kishi, Y. H 1987, 25, 97.
12. Nakata, T.; Schmid, G.; Vranesic, B.; Okigawa, M.; Smith-Palmer, T.; Kishi, Y. JACS 1978, 100, 2933.
13. Martin, S. F.; Grzejszczak, S.; Rüeger, H.; Williamson, S. A. JACS 1985, 107, 4072.
14. Brown, H. C.; Jadhav, P. K.; Bhat, K. S. JACS 1988, 110, 1535.

Joseph P. Vacca

Merck Research Laboratories, West Point, PA, USA

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