2-Bromo-3-trimethylsilyl-1-propene

[81790-10-5]  · C6H13BrSi  · 2-Bromo-3-trimethylsilyl-1-propene  · (MW 193.16)

(synthon for CH2=-CCH2TMS1-3 and CH2=CBr-CH2;2 for synthesis of 1-trimethylsilylmethyl-substituted 1,3-butadienes4)

Alternate Name: 2-bromoallyltrimethylsilane.

Physical Data: bp 46-50 °C/20 mmHg,3 64-65 °C/38-39 mmHg.1

Solubility: sol alcohol, acetone, ether, THF, pentane; insol water.

Preparative Methods: (1) reaction of 2,3-Dibromopropene with lithium (trimethylsilyl)cuprate in HMPA at 0 °C (63-90%);3,5 (2) reaction of 2,3-dibromopropene with Trichlorosilane in the presence of Triethylamine and Copper(I) Chloride, followed by treatment with Methylmagnesium Bromide (63-71%).1,3,6

Handling, Storage, and Precautions: no special requirements, except refrigeration in a brown bottle is recommended for long-term storage.

Synthon for CH2=-CCH2TMS.

The 1-trimethylsilylmethylvinyl anion CH2=C(M)CH2TMS (2) (M = Li, Mg, Cu, etc.), readily prepared from 2-bromo-3-trimethylsilyl-1-propene (1) under typical conditions, allows the introduction of the synthetically useful 1-trimethylsilylmethylvinyl group to a wide variety of substrates. Ring opening of 1-butene oxide with the Grignard reagent (2) (M = MgBr) in the presence of Copper(I) Iodide gives only one regioisomer. Subsequent desilylative oxidation of this allyl alcohol to a-methylene-g-lactones provides further utility of (1) as a 1-hydroxymethylvinyl anion equivalent, i.e. CH2=-CCH2OH (eq 1).1 Alternatively, the alcohol from trans-2,3-epoxybutane provides a route to the unstable six-membered b,g-unsaturated lactone (eq 2).7 The copper-catalyzed 1,4-addition to the typically unreactive mesityl oxide proceeds smoothly. The versatility of the allylsilane moiety is again illustrated in the Ethylaluminum Dichloride-induced cyclization of the adduct to a tertiary cyclopentanol in high yield (eq 3).2

Addition of (2) to a,o-substituted aldehydes and ketones is an efficient entry to inter- and intramolecular [3 + 2] cycloaddition approaches to methylenecyclopentanes.8 For example, chemoselective addition of the Grignard reagent (2) to the aldehyde (3), followed by acetylation and treatment with a palladium(0) catalyst, gives a bicyclo[3.3.0]octane (eq 4).3 Similarly, the ketosulfone (5), which derives from the lithium reagent (2) (M = Li) and the ketodithiane (4), cyclizes to the perhydroindanone system (eq 5).9 This methodology has also been extended to the synthesis of methylenetetrahydrofurans, e.g. in the formation of the phyllanthocin ring system (eq 6).10 Lewis acid-mediated cycloadditions, both inter- and intramolecular, have also been developed.11,12 An intermolecular case which generates the zizaene skeleton is depicted in eq 7.11

The tin analog of (2) (M = Me3Sn) undergoes smooth coupling with various aryl bromides and acyl chlorides to produce 2-substituted allylsilanes (eq 8).13 Interestingly, the organozinc reagent (2) (M = ZnCl) has been shown to equilibrate to the allyl isomer (6) and react as such with electrophiles to produce vinylsilanes.14a However, it is possible in some cases to control the product distribution with the choice of catalyst (eq 9).14b

Synthon for CH2=CBr-CH2.

Lewis acid-mediated addition of the silyl bromide (1) to electrophiles provides a convenient way to introduce the CH2=CBrCH2 moiety. In the case of carbonyl substrates, aldehydes react well while aliphatic ketones require higher concentration and aromatic ketones fail to participate. High stereoselectivity is achieved in many cases, e.g. in the addition to aldehyde (7). The subsequent conversion of the adduct by carbonylation to a a-methylene-g-butyrolactone illustrates the synthetic versatility of the vinyl bromide unit (eq 10).2 Conjugate addition to enones has also been demonstrated.2,15 In the case of 1-acetylcyclopentene, intramolecular Barbier reaction of the cis isomer of the adduct gives an excellent yield of the cyclopentanol (eq 11).2 Thus by combining the nucleophilic properties of the allylsilane with the ability to effect transmetalation of the vinyl bromide unit, the silyl bromide can serve also as a synthon for CH2=-C--CH2. Furthermore, the vinyl bromide moiety can be a source of a vinyl radical. The synthesis of a propellane ring skeleton is made possible using this strategy (eq 12).16

Under Lewis acidic conditions, the silyl bromide (1) and a,a-dimethoxylated amides undergo a [3 + 3] type annulation which is useful for the construction of the piperidine skeleton (eq 13).17 The silyl bromide (1) is also an excellent reagent for the stereoselective introduction of a functionalized allyl group at the anomeric center of the glucosides (eq 14).6,18

Coupling Reactions to Dienes and Enynes.

The silyl bromide (1) participates readily in copper or transition metal-mediated coupling reactions to produce 1,3-butadienes, which are very useful synthetic intermediates. For example, 2,3-bis[(trimethylsilyl)methyl]-1,3-butadiene (8), derived from the oxidative dimerization of cuprate (2) (M = Cu) is useful for rapid construction of multicyclic systems via tandem Diels-Alder reactions, as depicted in eq 15.19 The diene 2-dimethylaminomethyl-3-trimethylsilylmethyl-1,3-butadiene (9) functions similarly in the synthesis of a [6,7] ring system (eq 16).20

Nickel-catalyzed cross coupling of Grignard reagent (2) (M = MgBr) with other vinyl bromides provides an easy access to isoprenylsilanes that display high reactivity and regioselectivity toward various dienophiles, as illustrated in the synthesis of a dihydropyran (eq 17).4 Carbopalladation of allene with the silyl bromide (1) in the presence of a nucleophile also produces dienes. In one case the allylsilane unit is used to generate a cyclohexyl ring (eq 18).21

Palladium-catalyzed coupling of the silyl bromide to the terminal alkyne (10) gives the propargylic allylsilane (11), which is a key intermediate in the synthesis of a 10-membered cyclodiynol analog (12) of the antitumor agent neocarzinostatin (eq 19).22


1. Nishiyama, H.; Yokoyama, H.; Narimatsu, S.; Itoh, K. TL 1982, 23, 1267.
2. Trost, B. M.; Coppola, B. P. JACS 1982, 104, 6879.
3. Trost, B. M.; Grese, T. A.; Chan, D. M. T. JACS 1991, 113, 7350.
4. Hosomi, A.; Sakata, Y.; Sakurai, H. TL 1985, 26, 5175.
5. Smith, J. G.; Drozda, S. E.; Petraglia, S. P.; Quinn, N. R.; Rice, E. M.; Taylor, B. S.; Viswanathan, M. JOC 1984, 49, 4112.
6. Hosomi, A.; Sakata, Y.; Sakurai, H. Carbohydr. Res. 1987, 171, 223.
7. Isaac, K.; Kocienski, P.; Campbell, S. CC 1983, 249.
8. For an overview, see: (a) Chan, D. M. T. COS 1991, 5, 271. (b) Little, R. D. COS 1991, 5, 239. (c) Trost, B. M. AG(E) 1986, 25, 1. (d) Trost B. M. PAC 1988, 60, 1615.
9. Trost, B. M.; Grese, T. A. JOC 1992, 57, 686.
10. Trost, B. M.; Moeller, K. D. H 1989, 28, 321.
11. Hoffmann, H. M. R.; Eggert, U.; Gibbels, U.; Giesel, K.; Koch, O.; Lies, R.; Rabe, J. T 1988, 44, 3899.
12. (a) Ipaktschi, J.; Lauterbach, G. AG(E) 1986, 25, 354. (b) Collins, M. P.; Drew, M. G. B.; Mann, J.; Finch, H. JCS(P1) 1992, 3211.
13. Kang, K.-T.; Kim, S. S.; Lee, J. C. TL 1991, 32, 4341.
14. (a) Eshelby, J. J.; Crowley, P.; Parsons, P. J. SL 1993, 277, 279. (b) Minato, A.; Suzuki, K.; Tamao, K.; Kumada, M. TL 1984, 25, 83.
15. Ipaktschi, J.; Heydari, A. AG(E) 1992, 31, 313.
16. Jasperse, C. P.; Curran, D. P. JACS 1990, 112, 5601.
17. Shono, T.; Matsumura, Y.; Uchida, K.; Kobayashi, H. JOC 1985, 50, 3243.
18. Hosomi, A.; Sakata, Y.; Sakurai, H. TL 1984, 25, 2383.
19. Trost, B. M.; Shimizu, M. JACS 1982, 104, 4299.
20. Hosomi, A.; Otaka, K.; Sakurai, H. TL 1986, 27, 2881.
21. Cazes, B.; Colovray, V.; Gore, J. TL 1988, 29, 627.
22. Suffert, J. TL 1990, 31, 7437.

Dominic M. T. Chan

DuPont Agricultural Products, Newark, DE, USA



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