[42722-80-5]  · C3H5LiO  · 1-Methoxyvinyllithium  · (MW 64.02)

(acetyl anion equivalent; umpoled synthon; precursor to vinyl ethers)

Alternate Name: MVL.

Physical Data: white powder.

Solubility: sol THF, diethyl ether; insol alkanes; decomposes violently in protic solvents.

Analysis of Reagent Purity: the reagent reacts rapidly and quantitatively with chlorosilanes such as Chlorotrimethylsilane (TMSCl). To an aliquot of MVL solution at -78 °C, TMSCl (&egt;1 equiv) and n-decane standards are added. The yield of MVL is determined by GC analysis.

Preparative Methods: an ~1 M solution is prepared by the dropwise addition of t-Butyllithium (2 M) in pentane to a solution of methyl vinyl ether (2 M) in THF at ca. -78 °C, followed by slow warming (3 h) to 0 °C.2 The pure solid is prepared from the reaction of n-Butyllithium in hexanes (ca. 2 M) with tetrakis(a-methoxyvinyl)tin (ca. 0.5 M) in pentane at 0 °C.3 The precipitated lithium reagent is washed several times under an inert atmosphere with dry pentane to remove the tin impurities. The reagent can be isolated (>95%) or dissolved in ethereal solvents for subsequent reactions.

Handling, Storage, and Precautions: solid MVL is extremely dangerous, reacting explosively with atmospheric oxygen. Solutions of MVL can be pyrophoric and contact with atmosphere and moisture must be avoided. Individuals should thoroughly familiarize themselves with the special handling techniques required for such reagents prior to use.4

Nucleophilic Acylation and a-Alkoxyvinyllithium Reagents.

a-Methoxyvinyllithium is a very useful acetyl anion equivalent1 because it readily adds to a variety of electrophiles, and the resulting vinyl ether adducts are readily hydrolyzed to the acetyl derivatives under dilute acid conditions, normally in <1 h at 25 °C. In addition to methyl vinyl ether (MVE) and Ethyl Vinyl Ether (EVE), other vinyl ethers such as 1-propenyl, 1,3-dienyl, allenyl, and b-styryl ethers, but not b,b-disubstituted vinyl ethers, can also be a-lithiated.1,5 However, even under optimal conditions the deprotonations of MVE and EVE also produce minor amounts of dilithioacetylene (1-2%). Fortunately, tetrakis(a-methoxyvinyl)tin is formed free of alkynic impurities with a nominal excess of MVL because lithium acetylides are efficiently displaced from tin.3 Now available commercially, this tin reagent provides unsolvated MVL as a pure solid reagent from its reaction with n-butyllithium in hexanes through a simple transmetalation procedure. For research applications, MVL generated by this Sn/Li exchange method is superior to the reagent generated by the deprotonation of MVE both with respect to efficiency and product isolation (eq 1). The corresponding process for the preparation of 1-Ethoxyvinyllithium (EVL) is less efficient because of its greater solubility in pentane compared to MVL.6

Addition to Carbon Electrophiles.

MVL readily adds to aldehydes and ketones to give excellent yields of the corresponding a-methoxyvinyl carbinols.5a,7 Even ketones prone to enolization (e.g. phenylacetone, cyclopentanone) undergo smooth addition with high diastereofacial selectivity (e.g. eq 2).7k Moreover, 1,2-addition is observed with a,b-unsaturated aldehydes and ketones. The reagent undergoes double addition to esters to produce 3-hydroxy-2,4-pentanediones, which serve as highly useful precursors to 2-pyrazolin-4-ones (eq 3).8

Benzonitrile undergoes mainly monoaddition leading to a-diketones. MVL also adds to the carbonyl carbon of Phenacyl Bromide, producing an a-methoxyvinyl epoxide which is hydrolyzed to an acetylated vicinal diol (eq 4). In some cases (e.g. g,g-dimethylallyl bromide and 1-iodooctane), alkylation can be achieved, but Benzyl Bromide gives only 1,2-diphenylethane.5a

Organocuprates from MVL.

The preparation of the a-methoxyvinylcuprate reagent LiCu[C(OMe)=CH2]2 was first accomplished through the deprotonation of MVE followed by treatment with purified Copper(I) Iodide and added Dimethyl Sulfide as a complexing agent (see Lithium Bis(1-methoxyvinyl)cuprate).9 The analogous a-ethoxyvinylcuprate is prepared similarly (see Lithium Bis(1-ethoxyvinyl)cuprate). Both reagents undergo conjugate addition to a,b-unsaturated ketones, the process being less effective with b,b-disubstituted substrates (eq 5).10 The corresponding unsaturated aldehydes undergo 1,2-addition. Moreover, these reagents efficiently vinylate allylic and benzylic halides, but neither primary nor secondary bromides nor epoxycyclohexane produce satisfactory results. From the transmetalation procedure the higher order organocuprate Li2Cu(CN)[C(OMe)=CH2]2 is easily prepared from MVL and Copper(I) Cyanide in THF and this also undergoes allylation, providing 2-methoxy-1,4-pentadiene (eq 6), a useful intermediate for the preparation of either exo-brevicomin or frontalin in optically active form.11

a-Methoxyvinyl Derivatives of Group 14 Metalloids.

With the correct stoichiometry, the preparation of a-methoxyvinylsilanes, -germanes, and -stannanes from MVL and the metalloidal halide is a particularly efficient process (eq 7).12 From one to four a-methoxyvinyl groups can be introduced, with no limitations being encountered over a wide range of metalloidal substituents. However, an excess of the halometalloid with respect to MVL can result in the hydrolysis of the a-methoxyvinyl moiety. Moreover, with Chlorotrimethylstannane, an excess of MVL can also displace methyl groups from tin. While the deprotonation methodology gives excellent results under the proper conditions, the Sn/Li exchange route is superior for small scale reactions. The tin derivatives provide a simple access to MVL and also undergo smooth Stille coupling to produce a-methoxy enones.12 Mechanistic studies have demonstrated that the protonation of the vinyl ether moiety is rate-limiting with the rate increasing in the order: H < Si < Ge < Sn < C for a series of a-substituted a-methoxyvinyl compounds.13 Acetyl (e.g. 1) and even polyacetyl derivatives (e.g. 2) can also be prepared, but in the case of silanes, bulky substituents (e.g. i-Pr) are required to prevent product decomposition.14

Markovnikov Vinylboranes.

Early studies on the reaction of MVL (generated by deprotonation) implicated the intermediacy of internal (Markovnikov) vinylboranes.15 More recently, trialkylboranes have been found to undergo the clean addition of MVL (from Sn/Li exchange) to produce the organoborate complex which reacts efficiently with Me3SiCl to give the corresponding Markovnikov vinylboranes which are isolable in high yields (70-90%) (eq 8).16 Suzuki-Miyaura coupling of these boranes to alkenyl bromides occurs with complete retention of configuration, resulting in the efficient construction of stereodefined 1,3-dienes.17 Styrenes and enynes are similarly prepared.

N,N-Diethyl vinylcarbamate can also be smoothly a-metalated,18 but the organoborates derived from these reagents undergo rearrangment through a thermal rather than TMSCl-induced process.19

Related Reagents.

1,2-Dimethoxyvinyllithium; 1-Ethoxyvinyllithium.

1. (a) Seebach, D. AG(E) 1969, 8, 639. (b) Lever, O. W.; Jr. T 1976, 32, 1943. (c) Ager, D. J. In Umpoled Synthons; Hase, T. A., Ed.; Wiley: New York, 1987.
2. Soderquist, J. A. OS 1989, 68, 25.
3. (a) Soderquist, J. A.; Hsu, G. J.-H. OM 1982, 1, 830. (b) Soderquist, J. A.; Rivera, I.; Negron, A. JOC 1989, 54, 4051.
4. Brown, H. C.; Midland, M. M.; Levy, A. B.; Kramer, G. W. Organic Synthesis via Boranes; Wiley: New York, 1975.
5. (a) Baldwin, J. E.; Höfle, G. A.; Lever, O. W.; Jr. JACS 1974, 96, 7125. (b) Schöllkopf, U.; Hänssle, P. LA 1972, 763, 208. (c) Soderquist, J. A.; Hassner, A. JACS 1980, 102, 1577.
6. Rivera, I. Ph.D. Dissertation, University of Puerto Rico, 1992.
7. (a) Baldwin, J. E.; Lever, O. W., Jr.; Tzodikov, N. R. JOC 1976, 41, 2312. (b) Brimacombe, J. S.; Mather, A. M.; Hanna, R. TL 1978, 1171. (c) Wiseman, J. R.; French, N. I.; Hallmark, R. K.; Chiong, K. G. TL 1978, 3765. (d) Baldwin, S. W.; Mazzuckelli, T. J. TL 1986, 27, 5975. (e) Nomura, K.; Hori, K.; Ishizuka, M.; Yoshii, E. HC 1987, 25, 167. (f) Uyehara, T.; Suzuki, I.; Yamamoto, Y. TL 1989, 30, 4275. (g) Brimacombe, J. S.; Mather, A. M. JCS(P1) 1980, 269. (h) Cooke, M. P., Jr.; Goswami, R. JACS 1977, 99, 642. (j) Brimacombe, J. S.; Hanna, R.; Mather, A. M.; Weakley, T. J. R. JCS(P1) 1980, 273. (k) Hoppe, I.; Hoppe, D.; Wolff, C.; Egert, E.; Herbst, R. AG(E) 1989, 28, 67. For recent applications of the ethoxy analog, see: (l) Barrett, A. G. M.; Lebold, S. A. JOC 1990, 55, 5818. (m) Modi, S. P.; Michael, M. A.; Archer, S.; Carey, J. J. T 1991, 47, 6539. (n) Blechert, S.; Wirth, T. TL 1991, 32, 7237. (o) Bao, R.; Valverde, S.; Herradon, B. SL 1992, 217. (p) Kanda, Y.; Saito, H.; Fukuyama, T. TL 1992, 33, 5701.
8. Baldwin, J. E.; Lever, O. W., Jr.; Tzodikov, N. R. JOC 1976, 41, 2874.
9. Chavdarian, C. G.; Heathcock, C. H. JACS 1975, 97, 3822.
10. (a) Boeckman, R. K., Jr.; Bruza, K. J.; Baldwin, J. E. Lever, O. W., Jr. CC 1975, 519. (b) Boeckman, R. K., Jr.; Bruza, K. J. JOC 1979, 44, 4781. (c) Back, T. G.; Collins, S.; Krishna, M. V.; Law, K.-W. JOC 1987, 52, 4258. (d) Behling, J. R.; Babiak, K. A.; Ng, J. S.; Campbell, A. L.; Moretti, R.; Koerner, M.; Lipshutz, B. H. JACS 1988, 110, 2641.
11. (a) Santiago, B.; Soderquist, J. A. JOC 1992, 57, 5844. (b) Soderquist, J. A.; Rane, A. M. TL 1993, 34, 5031.
12. (a) Soderquist, J. A.; Hassner, A. JOM 1978, 156, C12. (b) Soderquist, J. A.; Leong, W. W.-H. TL 1983, 24, 2361. (c) Soderquist, J. A.; Rivera, I.; Negron, A. JOC 1989, 54, 4051. (d) Larson, G. L.; Soderquist, J. A.; Rivera-Claudio, M. SC 1990, 20, 1095. (e) Soderquist, J. A.; Anderson, C. L.; Miranda, E. I.; Rivera, I.; Kabalka, G. W. TL 1990, 31, 4677. (f) Buynak, J. D.; Strickland, J. B.; Lamb, G. W.; Khasnis, D.; Modi, S.; Williams, D.; Zhang, H. JOC 1991, 56, 7076. For the ethoxy analog, see: (g) Dexheimer, E. M.; Spialter, L. JOM 1976, 107, 229. (h) Nowick, J. S.; Danheiser, R. L. T 1988, 44, 4113. (i) Cunico, R. F.; Kuan, C. P. JOC 1992, 57, 3331.
13. (a) Soderquist, J. A.; Hassner, A. TL 1988, 29, 1899. (b) Kresge, A. J.; Tobin, J. B. JPOC 1991, 4, 587.
14. Lopez, C. J. Ph.D. Dissertation, University of Puerto Rico, 1993.
15. Levy, A. B.; Schwartz, S. J.; Wilson, N.; Christie, B. JOM 1978, 156, 123.
16. Soderquist, J. A.; Rivera, I. TL 1989, 30, 3919.
17. Rivera, I.; Soderquist, J. A. TL 1991, 32, 2311.
18. Tsukazaki, M.; Snieckus, V. TL 1993, 34, 411.
19. Birkinshaw, S.; Kocienski, P. TL 1991, 32, 6961.

John A. Soderquist & Leslie Castro-Rosario

University of Puerto Rico, Rio Piedras, Puerto Rico

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