[16532-02-8]  · C3H8BrClSi  · (Bromomethyl)chlorodimethylsilane  · (MW 187.54)

(allylic,2 propargylic,3 and homoallylic4 bromomethylsilyl ethers are used for regio- and stereoselective introduction of hydroxymethyl2-4 or methyl2c,d groups through radical cyclization; derivatizing agent for electron capture GC5)

Physical Data: bp 133-135 °C; bp 130 °C/740 mmHg; d204 1.386; n20D 1.466.

Solubility: sol most organic solvents including benzene, THF, methylene chloride, chloroform, and pyridine.

Form Supplied in: commercially available colorless liquid with 98% (GC) purity.

Analysis of Reagent Purity: GC analysis appears best; the following spectroscopic information may also be used: FTIR (vapor phase at 225 °C): 2978 (w), 1392 (w), 1264 (m), 822 (s) cm-1;6 1H NMR (CDCl3) d 0.58 (s, 6H), 2.65 (s, 2H); 13C NMR (CDCl3) d 0.27, 16.47.

Handling, Storage, and Precautions: moisture-sensitive; toxicological properties have not been thoroughly investigated; symptoms of exposure may include burning sensation, coughing, wheezing, laryngitis, shortness of breath, headache, nausea, and vomiting.7 Use in a fume hood.

Use as a Source of a-Silyl Radicals.

Treatment of hydroxy groups with (BrCH2)Me2SiCl in the presence of Triethylamine often with a catalytic amount of 4-Dimethylaminopyridine provides the (bromomethyl)dimethylsilyl ether derivatives in high yield. a-Silyl radicals generated from (bromomethyl)dimethylsilyl derivatives of cyclic allylic alcohols undergo highly regio- and stereoselective 5-exo radical cyclization reactions to provide the corresponding siloxanes (eq 1).2,8 These five-membered siloxanes can be efficiently oxidized to 1,3-diols2a-d,8 by the use of Tamao's conditions9 or cleaved to b-methyl alcohols with Potassium t-Butoxide-Dimethyl Sulfoxide (eq 1).2c,d Radicals generated from the (bromomethyl)dimethylsilyl ethers of acyclic alcohols also exhibit similar regioselectivity during radical cyclization.2a Formation of trans-3,4-disubstituted 1-sila-2-oxacyclopentanes is generally favored (eq 2).2a However, propensity toward increased 6-endo cyclization, as is observed in the cyclization of 2-sila-5-hexen-1-yl radicals,10 can be clearly manifested in certain a-silyl radicals (eq 3).2a,11 This 6-endo mode of cyclization is observed for a-silyl radicals with appropriate structural bias (eq 4).12 Detailed studies on the factors that affect these two competing modes of cyclization of allylic a-silyl radicals have resulted in the development of new methodology for the introduction of an angular hydroxymethyl group (eq 5).13,14

(Bromomethyl)dimethylsilyl propargylic ethers undergo highly regio-, stereo-, and chemoselective radical cyclization.3,15 The a-silyl radicals cyclize in a 5-exo fashion to provide siloxanes with an exocyclic alkene having trans stereochemistry between the newly formed C-C and C-H bonds (eq 6).15 This stereochemical preference is reversed when a substituent at the distal sp carbon is a TMS or phenyl group. When there are competing sites for addition between alkenic and alkynic carbons by the 5-exo-mode of cyclization, these a-silyl radicals preferentially attack an sp (5-exo-dig) over sp2 carbon (5-exo-trig).15

The mode of cyclization of a-silyl radicals generated from homoallylic (bromomethyl)dimethylsilyl ethers is highly dependent upon the substitution pattern on the distal alkenic carbon.4 Thus while those with unsubstituted distal alkene carbons provide seven-membered siloxanes (7-endo) (eq 7),4 those having substituted carbons undergo a 6-exo-mode of radical cyclization in a highly regio- and stereoselective manner (eq 8).4 These six-membered siloxanes provide, upon Tamao oxidation,9 branched chain 1,4-diols (eq 8).4

Generation of Chloro(lithiomethyl)dimethylsilane.

Treatment of (bromomethyl)chlorodimethylsilane in THF/ether with 1 equiv of n-Butyllithium in hexanes at -120 °C produces chloro(lithiomethyl)dimethylsilane. This lithiated derivative spontaneously eliminates LiCl to give an intermediate silaethylene species, which undergoes dimerization to afford 1,1,3,3-tetramethyl-1,3-disilacyclobutane (45%), together with a small amount of 1,1,3,3,5,5-hexamethyl-1,3,5-trisilacyclohexane (15%) (eq 9).16

Silazole Synthesis.

(Bromomethyl)dimethylsilyl derivatives obtainable from 2-mercaptoimidazoles and -benzimidazoles undergo cyclodehydrohalogenation, in the presence of a slight excess of a proton sponge (1,8-Bis(dimethylamino)naphthalene), providing silazoles (eq 10).17

1. (a) Curran, D. P. S 1988, 417. (b) Stork, G. BSF(2) 1990, 675.
2. (a) Nishiyama, H.; Kitajima, T.; Matsumoto, M.; Itoh, K. JOC 1984, 49, 2298. (b) Stork, G.; Kahn, M. JACS 1985, 107, 500. (c) Stork, G.; Sofia, M. J. JACS 1986, 108, 6826. (d) Stork, G.; Ma, R. TL 1989, 30, 3609.
3. Magnol, E.; Malacria, M. TL 1986, 27, 2255.
4. Koreeda, M.; Hamann, L. G. JACS 1990, 112, 8175.
5. Poole, C. F.; Zlatkis, A. J. Chromatogr. Sci. 1979, 17, 115.
6. Aldrich Library of FT-IR Spectra; Pouchert, C. J., Ed.; Aldrich: Milwaukee, 1989; Vol. 1 (3), p 1634C.
7. Sigma-Aldrich Library of Chemical Safety Data; Aldrich: Milwaukee, 1987; Vol. 2, p 548B.
8. (a) Kurek-Tyrlik, A.; Wicha, J.; Snatzke, G. TL 1988, 29, 4001. (b) Crimmins, M. T.; O'Mahony, R. JOC 1989, 54, 1157. (c) Bonnert, R. V.; Davies, M. J.; Howarth, J.; Jenkins, P. R. CC 1990, 148. (d) Majetich, G.; Song, J.-S.; Ringold, C.; Neumeth, G. A. TL 1990, 31, 2239. (e) Kurek-Tyrlik, A.; Wicha, J.; Zarecki, A.; Snatzke, G. JOC 1990, 55, 3484. (f) Majetich, G.; Song, J.-S.; Ringold, C.; Nemeth, G. A.; Newton, M. G. JOC 1991, 56, 3973. (g) Bonnert, R. V.; Davies, M. J.; Howarth, J.; Jenkins, P. R.; Lawrence, N. J. JCS(P1) 1992, 27. (h) Pedretti, V.; Mallet, J.-M.; Sinay, P. Carbohydr. Res. 1993, 244, 247.
9. (a) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. OM 1983, 2, 1694. (b) Tamao, K.; Ishida, N.; Kumada, M. JOC 1983, 48, 2120.
10. (a) Wilt, J. W. JACS 1981, 103, 5251. (b) Wilt, J. W. T 1985, 41, 3979. (c) Wilt, J. W.; Lusztyk, J.; Peeran, M.; Ingold, K. U. JACS 1988, 110, 281.
11. Lakomy, I.; Scheffold, R. HCA 1993, 76, 804.
12. (a) Koreeda, M.; George, I. A. JACS 1986, 108, 8098. (b) Koreeda, M.; George, I. A. CL 1990, 83.
13. Lejeune, J.; Lallemand, J. Y. TL 1992, 33, 2977.
14. Koreeda, M.; Visger, D. C. TL 1992, 33, 6603.
15. (a) Agnel, G.; Malacria, M. TL 1990, 31, 3555. (b) Journet, M.; Magnol, E.; Smadja, W.; Malacria, M. SL 1991, 58. (c) Journet, M.; Malacria, M. JOC 1992, 57, 3085. (d) Journet, M.; Malacria, M. TL 1992, 33, 1893.
16. Chmielecka, J.; Stanczyk, W. SL 1990, 344.
17. Alper, H.; Wolin, M. S. JOC 1975, 40, 437.

Masato Koreeda

University of Michigan, Ann Arbor, MI, USA

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