[31469-15-5]  · C8H18O2Si  · 1-Methoxy-2-methyl-1-(trimethylsilyloxy)propene  · (MW 174.35)

(functional equivalent of enolate of methyl isobutyrate; ester enolate surrogate in electrophilic reactions including alkylation,2 aldol reaction,3-5 Michael reaction,5a,6-8 initiator for group transfer polymerization of acrylates,9 nitroarylation,10 oxidation,11 dimerization,12 and cycloadditions13-15)

Alternate Name: dimethylketene methyl trimethylsilyl acetal.

Physical Data: bp 35 °C/15 mmHg; d 0.858 g cm-3.

Solubility: freely sol organic solvents.

Form Supplied in: clear colorless liquid; 95% pure.

Analysis of Reagent Purity: GC and NMR; likely impurities are methyl isobutyrate and hexamethyldisiloxane.

Handling, Storage, and Precautions: irritant; flammable; moisture sensitive; use in a fume hood.

General Considerations.

Ketene alkyl silyl acetals are functional equivalents of enolates of esters that can be readily prepared and stored. The title compound is a prototypical ketene silyl acetal (KSA) that can been prepared by either of the two most commonly employed methods: (a) deprotonation of the a-hydrogen of an ester followed by silylation (eq 1),16 and (b) metal-catalyzed hydrosilylation of a,b-unsaturated esters (eq 2).17

Most of the reactions of KSAs are characterized by the highly nucleophilic nature of this class of compounds. Under many reaction conditions they also serve as silylating agents, often facilitating product formation via the trapping of an unstable intermediate.10

Electrophilic Reactions.


Ketene silyl acetals readily undergo Lewis acid-mediated alkylation (eq 3) with alkylating agents that form stable carbenium ions (tertiary, benzylic, allylic, those carrying an a-oxygen, sulfur, or nitrogen).2 The reaction can be extended to primary alkylation by use of a-chloroalkyl phenyl sulfides which are valuable intermediates for not only alkylation but also alkylidenation.18 Examples of electrophiles (see Table 1) include alkyl glycosides,19 N-alkylhexahydro-1,3,5-triazine,20 a-acetoxy21 or a-sulfonyl amides,22 cationic h5-dienyliron complexes,23 electron-deficient pyridines,24 and elemental fluorine.25 Addition to dimethyl acetals5 give products which are protected aldol (eq 4) derivatives. Dibutyltin ditriflate can be used to activate acetals selectively in these type of reactions.26

Aldol Reactions: Addition to Aldehydes and Imines.

Since its discovery, the Mukaiyama aldol reaction27 has attracted considerable attention and several improvements in reaction conditions have been reported. Most useful catalysts for this reaction appear to be recently reported lanthanide triflates (eq 5),3 Bis(cyclopentadienyl)titanium Bis(trifluoromethanesulfonate), or Cp2Zr(OTf)2.THF.28 The metallocene salt also catalyzes additions to ketones (eq 6). This reaction can also be carried out under essentially neutral conditions by warming (70 °C) a stoichiometric mixture of the aldehyde and the KSA in acetonitrile (eq 7).8,29 When an optically active aldehyde is used, a slightly better stereochemical control is noticed under catalysis of Zinc Iodide.29

In the presence of an amino acid-derived boronate (e.g. 2)30 or a diamine-tin(II), complex,31 as Lewis acids, optically active aldol products are obtained in good yields (eq 8). In the addition of KSAs to iminies, a diphosphonium ditriflate32 (eq 9) or an acidic montmorillonite clay33 has been claimed to give better results than the originally reported Lewis acids (Titanium(IV) Chloride34 and Trimethylsilyl Trifluoromethanesulfonate35). The products of this reaction are valuable intermediates for the synthesis of b-lactams.36 Two excellent reviews covering this area have recently appeared.4,37

Mukaiyama-Michael Reactions.

1,4-Addition of ketene alkyl silyl acetals to a,b-unsaturated carbonyl compounds (eq 10) is promoted by a variety of Lewis acids38 (for example, TiCl4, Ti(OR)4, SnCl4, trityl perchlorate, lanthanide salts, Al-montmorillonite clay), or Lewis bases such as fluoride ion (eq 11),7 or quaternary ammonium carboxylates.39 Lanthanide salts are particularly effective catalysts,40 and in the case of Ytterbium(III) Trifluoromethanesulfonate, the catalyst can be recovered (eq 10).38

This reaction can also be carried out thermally,7,8 under neutral conditions. The thermal reaction is the most convenient when the conjugate adduct is to be trapped as the regiochemically pure silyl enolate. In the case of the disubstituted KSAs such as the title compound, this addition reaction is sluggish, and may require electrophilic catalysis (eq 11) (TMSCl,7 5.0 M LiClO4/Et2O41) or high pressure.42 Sequential Michael additions to a,b-unsaturated esters lead to polymers (group transfer polymerization) whose molecular weight and end group functionality can be controlled (eq 12).9 Mechanistic studies indicate an associative intramolecular silicon transfer process via (2), with concomitant C-C bond formation during the polymer growth. Other Michael-type reactions include additions to acetylenecarboxylic esters (eq 13),15,43 and nitroalkenes (eq 14).44 Stereochemical45 and mechanistic (electron transfer?)46 studies on the Mukaiyama-Michael reaction have been reported and ways of improving the diastereoselectivity have been prescribed.6


In the presence of stoichiometric amounts of Tris(dimethylamino)sulfonium Difluorotrimethylsilicate, (1) undergoes addition to aromatic nitro compounds to give dihydroaromatic nitro intermediates (eq 15), which are easily oxidized to a-nitroaryl carbonyl compounds by 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone or Bromine.10 These compounds are potentially useful for the synthesis of oxindoles and aryl acetic acids.

Oxidation of Ketene Silyl Acetals.

Singlet oxygen oxidizes KSAs resulting in a cleavage of C-C bonds (eq 16),47 the reaction presumably proceeding through a silyl peroxide intermediate. Lead(IV) Acetate11 and m-Chloroperbenzoic Acid48 oxidize KSAs to a-acetoxy (or hydroxy) carboxylic acid derivatives. Oxidative dimerization of ketene silyl acetals by TiCl4 (eq 17)12 can be understood in terms of single-electron transfer to the Lewis acids.49

Cycloaddition Reactions of Ketene Silyl Acetals.

In the presence of Zirconium(IV) Chloride, KSA adds to ethyl propiolate in a [2 + 2] fashion (eq 18).15 Other cycloaddition reactions include cycloaddition to imines (eq 19),13 addition of Ethyl Azidoformate,14 chlorovinylcarbene,50 and (ethoxycarbonyl)nitrene.51 Synthesis of b-lactams from KSAs and imines have attracted considerable attention and the subject has been reviewed recently.4,37 Cyclopropanation of KSAs with Et2Zn/CH2I2 to provide cyclopropanone acetals is also known (eq 20).52

Related Reagents.

t-Butyl a-Lithioisobutyrate; Dilithioacetate; Ethyl Lithioacetate; Ketene Bis(trimethylsilyl) Acetal; Ketene t-Butyldimethylsilyl Methyl Acetal; 1-Methoxy-1-(trimethylsilyloxy)propene; 1-Methoxy-2-trimethylsilyl-1-(trimethylsilyloxy)ethylene; Tris(trimethylsilyloxy)ethylene.

1. (a) Colvin, E. W. In The Chemistry of the Metal-Carbon Bond; Hartley, F. R., Ed.; Wiley: Chichester, 1987; Vol. 4, p 539. (b) Weber, W. P. Silicon Reagents for Organic Synthesis; Springer: Berlin, 1983. (c) Mukaiyama, T. OR 1982, 28, 203. (d) Brownbridge, P. S 1983, 1. (e) Brownbridge, P. S 1983, 85.
2. (a) Reetz, M. T. AG(E) 1982, 21, 96. (b) Reetz, M. T.; Schwellnus, K.; Hubner, F.; Massa, W.; Schmidt, R. E. CB 1983, 116, 3708.
3. Kobayashi, S.; Hachiya, I.; Takahori, T. S 1993, 371. For earlier work on related lanthanides, see Ref. 6 of this article. See also: Van de Weghe, P.; Collin, J. TL 1993, 34, 3881. Mikami, K.; Terada, M.; Nakai, T. CC 1993, 343.
4. Gennari, C. COS 1991, 2, 629.
5. (a) Mukaiyama, T.; Kobayashi, S. JOM 1990, 382, 39. For the use of other Lewis acids in aldol-type reactions see: (b) Montmorillonite clay (Al3+): Kawai, M.; Onaka, M.; Izumi, Y. BCJ 1988, 61, 1237. (c) TMSOTf: Murata, S.; Suzuki, M.; Noyori, R. T 1988, 44, 4259. (d) Bu2Sn(OTf)2: Sato, T.; Otera, J.; Nozaki, H. JACS 1990, 112, 901.
6. Otera, J.; Fujita, Y.; Sato, T.; Nozaki, H. JOC 1992, 57, 5054.
7. RajanBabu, T. V. JOC 1984, 49, 2083. See also: Refs. 5(a) and 39.
8. (a) Kita, Y.; Segawa, J.; Haruta, J.; Fuji, T.; Yasuda, H.; Tamura, Y. JCS(P1) 1982, 1099. For the use of nitromethane as a solvent, see Ref. 7. (b) A recent report (Berl, V.; Helmchen, G.; Preston, S. TL 1994, 35, 233) questions the role of the solvent (acetonitrile) and suggests phosphorus-containing impurities as responsible for the catalysis of this reaction. Indeed, these workers find that P4O10 is a good catalyst for the reaction! In light of this observation, the thermal aldol reaction, shown in eq 7, may also have to be reinvestigated.
9. Webster, O. W.; Hertler, W. R.; Sogah, D. Y.; Farnham, W. B.; RajanBabu, T. V. JACS 1983, 105, 5706; J. Macromol. Sci., Chem. 1984, A21, 943.
10. (a) RajanBabu, T. V.; Reddy, G. S.; Fukunaga, T. JACS 1985, 107, 5473. (b) RajanBabu, T. V.; Chenard, B. L.; Petti, M. A. JOC 1986, 51, 1704.
11. Rubottom, G. M.; Gruber, J. M.; Marrero, R.; Juve, H. D., Jr.; Kim, C. W. JOC 1983, 48, 4940.
12. (a) Inaba, S.; Ojima, I. TL 1977, 2009. (b) Hirai, K.; Ojima, I. TL 1983, 24, 785.
13. Ojima, I.; Inaba, S. TL 1980, 21, 2081. For applications involving KSAs from N-methylephedrine esters, see Gennari, C.; Schimperna, G.; Venturini, I. T 1988, 44, 4221.
14. Cipollone, A.; Loretto, M. A.; Pellacani, L.; Tardella, P. A. JOC 1987, 52, 2584.
15. Quendo, A.; Rousseau, G. TL 1988, 29, 6443.
16. Ainsworth, C.; Chen, F.; Kuo, Y. JOM 1972, 46, 59. KSAs can also be prepared from a-halo esters using Na and TMSCl: Schulz, W. J., Jr.; Speier, J. L. S 1989, 163.
17. (a) Revis, A.; Hilty, T. K. JOC 1990, 55, 2972. (b) See also: Yoshii, E.; Kobayashi, Y.; Koizumi, T.; Oribe, T. CPB 1974, 22, 2767.
18. Paterson, I. T 1988, 44, 4207.
19. Reetz, M. T.; Muller-Starke, H. LA 1983, 1726.
20. Ikeda, K.; Achiwa, K.; Sekiya, M. TL 1983, 24, 913.
21. Kita, Y.; Shibata, N.; Tohjo, T.; Yoshida, N. JCS(P1) 1992, 1795.
22. Brown, D. S.; Hansson, T.; Ley, S. V. SL 1990, 1, 48. See also: (a) Brown, D. S.; Bruno, M.; Ley, S. V. H 1989, 28 (Special Issue No. 2), 773. (b) Ley, S. V.; Lygo, B.; Sternfeld, F.; Wonnacott, A. T 1986, 42, 4333.
23. Pearson, A. J.; O'Brien, M. K. TL 1988, 29, 869.
24. Onaka, M.; Ohno, R.; Izumi, Y. TL 1989, 30, 747.
25. Purrington, S. T.; Woodard, D. L. JOC 1990, 55, 3423.
26. Sato, T.; Otera, J.; Nozaki, H. JACS 1990, 112, 901.
27. Mukaiyama, T. OR 1982, 28, 203.
28. Hollis, T. K.; Robinson, N. P.; Bosnich, B. TL 1992, 33, 6423. See also: Hong, Y.; Norris, D. J.; Collins, S. JOC 1993, 58, 3591. Hollis, T. K.; Bosnich, B. JACS 1995, 117, 4750.
29. Kita, Y.; Tamura, O.; Itoh, F.; Yasuda, H.; Kishino, H.; Ke, Y. Y.; Tamura, Y. JOC 1988, 53, 554. The rate of this aldol reaction is accelerated by incorporating the silicon in a four-membered ring: Myers, A. G.; Kephart, S. E.; Chen, H. JACS 1992, 114, 7922.
30. Kiyooka, S.; Kaneko, Y.; Kume, K. TL 1992, 33, 4927.
31. Mukaiyama, T.; Kobayashi, S.; Sano, T. T 1990, 46, 4653.
32. Mukaiyama, T.; Kashiwagi, K.; Matsui, S. CL 1989, 1397.
33. Onaka, M.; Ohno, R.; Yanagiya, N.; Izumi, Y. SL 1993, 141.
34. Ojima, I.; Inaba, S.; Yoshida, K. TL 1977, 3643.
35. Guanti, G.; Narisano, E.; Banfi, L. TL 1987, 28, 4331.
36. Colvin, E. W.; McGarry, D.; Nugent, M. J. T 1988, 44, 4157. For the corresponding Li enolate version see: Ha, D.-C.; Hart, D. J.; Yang, T.-K. JACS 1984, 106, 4819.
37. Kleinman, E. F. COS 1991, 2, 893.
38. Kobayashi, S.; Hachiya, I.; Takahori, T.; Araki, M.; Ishitani, H. TL 1992, 33, 6815.
39. Klimko, P. G.; Singleton, D. A. JOC 1992, 57, 1733. For the use of Montmorillonite clay, see: Kawai, M.; Onaka, M.; Izumi, Y. BCJ 1988, 61, 2157.
40. Van de Weghe, P.; Collin, J. TL 1993, 34, 3881.
41. Grieco, P. A.; Cooke, R. J.; Henry, K. J.; VanderRoest, J. M. TL 1991, 32, 4665.
42. Yamamoto, Y.; Maruyama, K.; Matsumoto, K. TL 1984, 25, 1075. See also Bunce, R. A.; Schlecht, M. F.; Dauben, W. G.; Heathcock, C. H. TL 1983, 24, 4943.
43. Kelly, T. R.; Ghoshal, M. JACS 1985, 107, 3879. See also for montmorillonite catalysis Onaka, M.; Mimura, T.; Ohno, R.; Izumi, Y. TL 1989, 30, 6341.
44. Miyashita, M.; Yanami, T.; Kumazawa, T.; Yoshikoshi, A. JACS 1984, 106, 2149.
45. Heathcock, C. H.; Norman, M. H.; Uehling, D. E. JACS 1985, 107, 2797.
46. Sato, T.; Wakahara, Y.; Otera, J.; Nozaki, H.; Fukuzumi, S. JACS 1991, 113, 4028.
47. Wasserman, H. H.; Lipshutz, B. H.; Wu, J. S. H 1977, 7, 321. See also: Adam, W.; del Fierro, J. JOC 1978, 43, 1159.
48. Rubottom, G. M.; Marrero, R. SC 1981, 11, 505.
49. Fukuzumi, S.; Fujita, M.; Otera, M.; Fujita, Y. JACS 1992, 114, 10271.
50. Slougui, N.; Rousseau, G. TL 1987, 28, 1651.
51. Loreto, M. A.; Pellacani, L.; Tardella, P. A. JCR(S) 1988, 304.
52. Rousseau, G.; Slougui, N. TL 1983, 24, 1251.

T. V. (Babu) RajanBabu

The Ohio State University, Columbus, OH, USA

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