[18388-03-9]  · C7H15ClSi  · 2-Chloromethyl-3-trimethylsilyl-1-propene  · (MW 162.73)

(bifunctional electrophilic and nucleophilic reagent displaying reactions characteristic of both allylsilanes and allyl halides; useful for exomethylene annulation reactions)

Physical Data: bp 162-163 °C/768 mmHg; d 0.899 g cm-3; n 1.4540.

Solubility: insol water; miscible with organic solvents.

Form Supplied in: colorless liquid; commercially available.

Analysis of Reagent Purity: 1H NMR (CDCl3) d 4.99 (s, 1H), 4.75 (s, 1H), 3.96 (s, 2H), 1.68 (s, 2H), 0.04 (s, 9H); 13C NMR (CDCl3) d 143.0, 112.3, 49.9, 23.6, -1.5.1

Preparative Methods: from 3-chloro-2-methyl-1-propene,2 from (Iodomethyl)trimethylsilane,3 from 2-(hydroxymethyl)-3-trimethylsilyl-1-propene,4 from 3-chloro-2-(chloromethyl)-1-propene and Trichlorosilane,5 and from Methyl Chloroacetate.1,6

Handling, Storage, and Precautions: flammable liquid (flash point 43 °C). Storage at 4 °C under N2 advised. Handle under N2. May be harmful by inhalation, ingestion, or skin absorption. Vapor or mist is irritating to the eyes, mucous membranes, and upper respiratory tract. Causes skin irritation. Toxicological properties not thoroughly investigated. Use in a fume hood.

Characterization of Reagent.

This reagent, 2-chloromethyl-3-trimethylsilyl-1-propene (1), at once an allyl chloride and allylsilane, is best considered as a synthetic equivalent of the zwitterion (2).

Methylenecyclopentane 3,4-Annulation with Enones.

By virtue of the fact that the electrophilic and nucleophilic reactivities of (1) are triggered under well differentiated conditions, this reagent has found some utility for cyclopentane annulation in which the ring is invariably constructed by a two-step process. This was first demonstrated by Knapp et al. with the methylenecyclopentane annulation of cyclic enones (3) (eqs 1 and 2).3,7

This sequence makes use of the ability of allylsilanes to undergo the Michael reaction with a,b-unsaturated ketones under Lewis acidic conditions (eq 1) (see Allyltrimethylsilane). Best results are achieved with a-phenylthio substitution; the sensitive cyclopentenone (3a) suffers extensive polymerization during this step. Cyclization is then achieved by base treatment (eq 2). In the case of (4c) a 3:1 mixture of isomers results, but the predominant diastereoisomer of (5c) is not characterized. These results contrast with those obtained by Trost and Chan with the trimethylenemethane complex (6) (eq 3).8 This reagent generated in situ from 3-Acetoxy-2-trimethylsilylmethyl-1-propene in the presence of a palladium catalyst accomplishes the methylenecyclopentane annulation with a variety of activated alkenes in one step under mild conditions (eqs 3 and 4).9 A good yield (60%) is obtained in this concerted reaction with cyclopentenone, although poor yields are observed with cyclohex-2-enone and cyclohept-2-enone, in contrast to Knapp's two-step sequence.7,9-11

1,2-Aldehyde Addition Reactions.

The allylsilane reactivity of (1) with aldehydes under Lewis acid conditions (eq 5) forms the basis of another mode of annulation, furnishing either 3-methylenetetrahydrofurans (8) (eq 6) or a-methylenebutyrolactones (9) (eq 7).12

The first step proceeds under catalysis by Boron Trifluoride Etherate in the preferred solvent chloroform to give homoallyl alcohols (10) in good yield (eq 5). Cyclization to the ether (8) is accomplished by treatment with 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) in the presence of Lithium Perchlorate (eq 6). The equivalent transformation has been more commonly achieved in one step in generally high yields by use of 3-acetoxy-2-trimethylsilylmethyl-1-propene (eq 8)13,14 or 2-trialkylstannylmethyl-3-trimethylsilyl-1-propene in the presence of a palladium catalyst.15,16

Alternatively, (10) may be oxidized to a carboxylic acid; cycloesterification with Trifluoromethanesulfonic Anhydride then yields a-methylenebutyrolactones (9) (eq 7).12 This same transformation has also been demonstrated in one step using 2-(bromomethyl)acrylic acid17b or its ethyl ester under reducing conditions (eq 9).17

The same authors have described the addition of (1) to protected a-aminoaldehydes to give amino alcohols with high levels of diastereoselectivity in moderate to good yields (eq 10).18,19 They report isolation of a single diastereoisomer following chromatographic purification.


An interesting example of the use of (1) for the construction of a six-membered ring has been demonstrated by Guiles and Meyers (eq 11).20 Tetrahydroisoquinoline alkylation with (1) occurred with high enantioselectivity. Following deprotection, cyclization was initiated in the presence of fluoride ion with formaldehyde. A racemic product was obtained due to the reversible aza-[3,3]-sigmatropic rearrangement of the iminium ion intermediate.

A few examples have appeared in the literature in which solely the electrophilic character of (1) has been utilized;21-23 in this respect, 2-mesyloxymethyl-3-trimethylsilyl-1-propene has found more general usage.11

1. Lee, T. V.; Channon, J. A.; Cregg, C.; Porter, J. R.; Roden, F. S.; Yeoh, H. T.-L. T 1989, 45, 5877.
2. Petrov, A. D.; Nikishin, G. I. BAU 1956, 233 (CA 1956, 50, 13 726g).
3. Knapp, S.; O'Conner, U.; Mobilio, D. TL 1980, 21, 4557.
4. Jones, M. D.; Kemmitt, R. D. W.; Platt, A. W. G. JCS(D) 1986, 1411.
5. Trost, B. M.; Buch, M.; Miller, M. L. JOC 1988, 53, 4887.
6. Lee, T. V.; Porter, J. R.; Roden, F. S. TL 1988, 29, 5009.
7. Ramaiah, M. S 1984, 529.
8. Trost, B. M.; Chan, D. M. T. JACS 1979, 101, 6429.
9. Cossy, J.; Belotti, D.; Pete, J. P. T 1990, 46, 1859.
10. Trost, B. M.; Chan, D. M. T. JACS 1983, 105, 2315.
11. Trost, B. M. AG(E) 1986, 25, 1.
12. D'Aniello, F.; Mattii, D.; Taddei, M. SL 1993, 119.
13. Trost, B. M.; King, S. A. TL 1986, 27, 5971.
14. Trost, B. M.; King, S. A.; Schmidt, T. JACS 1989, 111, 5902.
15. Trost, B. M.; Bonk, P. J. JACS 1985, 107, 1778.
16. Trost, B. M.; Bonk, P. J. JACS 1985, 107, 8277.
17. (a) Nokami, J.; Tamaoka, T.; Ogawa, H.; Wakabayashi, S. CL 1986, 541. (b) Uneyama, K.; Udea, K.; Torii, S. CL 1986, 1201. (c) Okuda, Y.; Nakatsukasa, S.; Oshima, K.; Nozaki, H. CL 1985, 481. (d) Mattes, H.; Benezra, C. TL 1985, 26, 5697. (e) Heindel, N. D.; Minatelli, J. A. JPS 1981, 70, 84. (f) Rosenberg, S. H.; Dellaria, J. F.; Kempf, D. J.; Hutchins, C. W.; Woods, K. W.; Maki, R. G.; de Lara, E.; Spina, K. P.; Stein, H. H.; Cohen, J.; Baker, W. R.; Plattner, J. J.; Kleinert, H. D.; Perun, T. J. JMC 1990, 33, 1582.
18. D'Aniello, F.; Taddei, M. JOC 1992, 57, 5247.
19. D'Aniello, F.; Géhanne, S.; Taddei, M. TL 1992, 33, 5621.
20. Guiles, J. W.; Meyers, A. I. JOC 1991, 56, 6873.
21. Molander, G. A.; Shubert, D. C. TL 1986, 27, 787.
22. Dombroski, M. A.; Kates, S. A.; Snider, B. B. JACS 1990, 112, 2759.
23. Camps, F.; Moreto, J. M.; Pagés, L. T 1992, 48, 3147.

Jotham W. Coe & David A. Perry

Pfizer, Groton, CT, USA

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