[22612-89-1]  · C3H2Br4O  · 1,1,3,3-Tetrabromoacetone  · (MW 373.65)

(a good source of the 1,3-dibromooxyallyl cation, a synthetic equivalent of the oxyallyl cation; especially useful for [4 + 3] cycloadditions1)

Alternate Name: 1,1,3,3-tetrabromopropanone.

Physical Data: bp 129-130 °C;7 mp 37-38 °C.

Solubility: sol moderately polar to polar organic solvents.

Form Supplied in: not commercially available and should be prepared as needed.2

Analysis of Reagent Purity: assay by NMR.2

Handling, Storage, and Precautions: powerful lachrymator; use in a fume hood. If contact with the skin occurs the affected area should be thoroughly washed with soap followed by a solution of sodium bicarbonate.3

[4 + 3] Cycloadditions.

The chemistry of 1,1,3,3-tetrabromoacetone (1) is dominated by its ability to form oxyallylic cation (2) and related species under a variety of conditions (eq 1). This intermediate has been exploited essentially exclusively as a dienophile in [4 + 3] cycloadditions with dienes, in which it serves as an equivalent of the elusive parent oxyallyl (3).1 1,1,3,3-Tetrabromoacetone serves as a prototype for other polyhalogenated ketones which exhibit similar chemistry.

A number of reagents have been utilized to effect the conversion of (1) to (2). These include Diethylzinc,4 Nonacarbonyldiiron,1d Pentacarbonyliron,1c,5 zinc/triethyl borate,6 Zinc/Copper Couple,7 and Zinc/Silver Couple.8 The nature of these reagents precludes the formation of (2) in free form and suggests the inclusion of metal counterions which can be expected to attenuate the reactivity of (2) in combination with solvent and other effects. It is important to note that 1,3-dibromoacetone has not been successfully used to directly access (3).1c

The majority of [4 + 3] cycloadditions using (2) have involved furans as reaction partners. The reaction of (2) with furan to form 8-oxabicyclo[3.2.1]-6-octen-3-one (4) is illustrative (eq 2). Nearly all the aforementioned reagents have been used to generate (2) for this reaction. Some of the reactions have been conducted quite successfully on a large scale (Table 1).4,6,8 -10 The initial cycloadducts contain bromine, which is removed using a reductive debromination with zinc/copper couple.

Adducts derived from (2) and various furans have been used in the synthesis of analogs of thromboxane,8 cocaine,11 and muscarine,12 among others. A general synthesis of tropanes from such cycloadducts has been developed.13 For example, nezukone (6) could be prepared in fair overall yield in three steps from cycloadduct (5) (eq 3).

Among the most interesting and important applications of cycloadducts derived from (2) has been the synthesis of a family of structurally diverse ribo-C-nucleosides.14 Examples include (7)-(9), all of which are ultimately derived from (1) and the appropriate furan.14

Oxyallyl (2) has also been used in reactions with pyrroles to produce analogs of tropane alkaloids (eq 4).4,7 Trapping with dienes such as Cyclopentadiene5,6,9,15 and substituted anthracenes16 has been studied as well (eqs 5 and 6).

Other Routes to Equivalents of (3).

Several synthetic routes to equivalents of (3) are known. 2-Methoxy-3-bromopropene, for example, undergoes a reaction with Furan in the presence of silver ion to give (4) in low yield (eq 7).17 Presumably, the cation (10) is an intermediate. This intermediate is so reactive that it even gives [4 + 3] cycloaddition products with benzene.18

The reaction of the trimethylsilyl enol ether of 1,3-dichloroacetone (11) with furan in the presence of Silver(I) Perchlorate gave an 80% yield of a mixture of cycloadducts (eq 8).19 These could undoubtedly be converted to (3) via reductive dehalogenation. While the use of silver salts makes this process expensive, the ready availability of (11) renders this method attractive.

Finally, tetrachloro- and pentachloroacetone have been shown to give rise to oxyallylic cations capable of [4 + 3] cycloaddition with furan. Triethylamine in methanol, triethylamine or sodium trifluoroethoxide in trifluoroethanol/furan, and triethylamine in ethereal lithium perchlorate have been used in this reaction (eqs 9 and 10).20 The cycloadducts in these cases could be dehalogenated to (4). This approach has been recognized as particularly convenient, since tetrachloroacetone is more easily handled than (1).1b

Favorsky Rearrangement.

Treatment of (1) with 1 M sodium bicarbonate resulted in a Favorsky rearrangement to yield b,b-dibromoacrylic acid in good yield (eq 11).21

Related Reagents.

2,4-Dibromo-3-pentanone; Diethylzinc; 2-Methoxyallyl Bromide; Zinc/Copper Couple; Zinc/Silver Couple.

1. (a) Hosomi, A.; Tominaga, Y. COS 1991, 5, 593. (b) Mann, J. T 1986, 42, 4611. (c) Hoffmann, H. M. R. AG(E) 1984, 23, 1. (d) Noyori, R.; Hayakawa, Y. OR 1983, 29, 163. (e) Noyori, R. ACR 1979, 12, 61. (f) Hoffmann, H. M. R. AG(E) 1973, 12, 819.
2. Rappe, C. AK 1963, 21, 503.
3. Ashcroft, M. R.; Hoffmann, H. M. R. OSC 1988, 6, 512.
4. Mann, J.; Barbosa, L. C. A. JCS(P1) 1992, 787.
5. Siemionko, R. K.; Berson, J. A. JACS 1980, 102, 3870.
6. Hoffmann, H. M. R.; Iqbal, M. N. TL 1975, 4487.
7. Hayakawa, Y.; Baba. Y.; Makino, S.; Noyori, R. JACS 1978, 100, 1786.
8. Ansell, M. F.; Mason, J. S.; Caton, M. P. L. JCS(P1) 1984, 1061.
9. Takaya, H.; Makino, S.; Hayakawa, Y.; Noyori, R. JACS 1978, 100, 1765.
10. Sato, T.; Noyori, R. BCJ 1978, 51, 2745.
11. Kainz, A.; Eider, F. AP 1990, 323, 191.
12. Cowling, A. P.; Mann, J.; Usmani, A. A. JCS(P1) 1981, 2116.
13. Takaya, H.; Hayakawa, Y.; Makino, S.; Noyori, R. JACS 1978, 100, 1778.
14. (a) Sato, T.; Watanabe, M.; Kobayashi, H.; Noyori, R. BCJ 1983, 56, 2680. (b) Sato, T.; Kobayashi, H.; Noyori, R. H 1981, 15, 321. (c) Sato, T.; Noyori, T. TL 1980, 2535. (d) Sato, T.; Kobayashi, H.; Noyori, R. TL 1980, 1971. (e) Sato, T.; Watanabe, M.; Noyori, R. TL 1979, 2897.
15. Wierenga, W.; Evans, B. R.; Woltersom, J. A. JACS 1979, 101, 1334.
16. Hoffmann, H. M. R.; Karama, U. CB 1992, 125, 2803.
17. Hill, A. E.; Greenwood, G.; Hoffmann, H. M. R. JACS 1973, 95, 1338.
18. Hill, A. E.; Hoffmann, H. M. R. JACS 1974, 96, 4597.
19. Shimizu, N.; Tanaka, M.; Tsuno, Y. JACS 1982, 104, 1330.
20. (a) Herter, R.; Fohlisch, B. S 1982, 976. (b) Fohlisch, B.; Gehrlach, E.; Herter, R. AG(E) 1982, 241. (c) Fohlisch, B.; Gottstein, W.; Herter, R.; Wanner, I. JCR(S) 1981, 246.
21. Rappe, C.; Andersson, D. ACS 1969, 23, 2839.

Michael Harmata

University of Missouri-Columbia, MO, USA

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