[115-19-5]  · C5H8O  · 2-Methylbut-3-yn-2-ol  · (MW 84.13)

(monoprotected alkyne;1 undergoes Claisen rearrangements to conjugated dienoates and dienones)

Physical Data: mp 2.6 °C; bp 104 °C; d 0.868 g cm-3.

Solubility: miscible with H2O, alcohols, benzene, EtOAc, petroleum ethers.

Form Supplied in: colorless liquid; widely available. Drying: removal of residual water by azeotropic distillation (bp 90.7 °C, 28.4% H2O).1b

Monoprotected Alkyne.

2-Methylbut-3-yn-2-ol (MB) has been used extensively as an alkyne equivalent in the preparation of arylalkynes and unsymmetrical diarylalkynes; acetylene itself leads to mixtures. These products are used mainly in the polymer or liquid crystal field. MB is a cheap alternative to Trimethylsilylacetylene,2 in the presence of which it may be selectively cleaved.3 After palladium-catalyzed coupling of MB with an aromatic halide, the terminal alkyne function can be unmasked by heating in the presence of base; removal of acetone by distillation drives the reaction to completion (eq 1). One-pot procedures have been developed.4 The methodology has been used on a wide range of aromatic5 and heteroaromatic6 halides (reactivity I > Br > Cl) as well as vinyl halides7 and triflates.8 Yields are good (normally 60-80% for the two steps) and most functionalities are compatible (aldehydes must be protected)5 with the reaction conditions. When the coupling takes place ortho to a hydroxy or an amino group, benzofurans9 and indoles10 can result.

Oxidative Coupling with Alkynes.

Treatment of MB with Copper(I) Chloride in the presence of oxygen followed by heating the product with NaOH in xylene gives 1,3-butadiyne (diacetylene) in 80% yield.11 Nonsymmetrical 1,3-diynes are produced from the coupling of MB with haloalkynes in the presence of CuI salts (Cadiot-Chodkiewicz coupling). Acetone can of course be removed as mentioned to allow further manipulation (eq 2).12

Claisen Rearrangements and Isomerizations.

Reaction of 2-methylbut-3-yn-2-ol with orthoesters gives, after Claisen rearrangement and isomerization of the allenes thus formed, 5-methyl hexa-2,4-dienoates,13 useful in the preparation of alkyl chrysanthemates.14 Similarily, reaction with enol ethers gives 6-methyl-3,5-dien-2-ones with trans selectivity (eq 3).15 Isomerization (Meyer-Schuster rearrangement) of 2-methylbut-3-yn-2-ol in the presence of a titanium/copper-based catalyst gives 3-methyl-2-butenal in good yield (83%) (eq 4).16 Partial hydrogenation gives 2-methylbut-3-en-2-ol.17 Both of these compounds are of use in the synthesis of vitamin K-type products.18

Chromene Preparation.

3-Chloro-3-methyl-1-butyne19 (prepared with MB/HCl/CuCl2, yield 69%) is the reagent of choice for the preparation of the chromene system in potassium-channel blockers such as cromakalim (eq 5).20

Related Reagents.

Acetylene; (Trimethylsilyl)ethynylcopper(I); Dilithium Acetylide; Ethynyldimethylaluminum; Dipotassium Acetylide; Ethynylmagnesium Bromide; Lithium Acetylide; Lithium (Trimethylsilyl)acetylide; Trimethylsilylacetylene.

1. (a) FF 1967, 1, 674. (b) Budavari, S. Merck Index, 11th ed.; Merck: Rahway, NJ, 1989; p 951.
2. Austin, W. B.; Bilow, N.; Kelleghan, W. J.; Lau, K. S. Y. JOC 1981, 46, 2280.
3. Neenan, T. X.; Whitesides, G. M. JOC 1988, 53, 2489.
4. Carpita, A.; Lessi, A.; Rossi, R. S 1984, 571.
5. Havens, S. J.; Hergenrother, P. M. JOC 1985, 50, 1763.
6. Ames, D. E.; Bull, D.; Takundwa, C. S 1981, 364.
7. Andreini, B. P.; Carpita, A.; Rossi, R.; Scamuzzi, B. T 1989, 45, 5621.
8. Brueckner, R.; Scheuplein, S. W.; Suffert, J. TL 1991, 32, 1449.
9. Kundu, N. G.; Pal, M.; Mahanty, J. S.; Dasgupta, S. K. CC 1992, 41.
10. Piskunov, A. V.; Moroz, A. A.,; Shvartsberg, M. S. IZV 1990, 1441.
11. Tedeschi, R. J.; Brown, A. E. JOC 1964, 29, 2051.
12. (a) Tronchet, J.-M. J; Bonenfant, A. P. HCA 1981, 64, 1893. (b) Blanco, L.; Helson, H. E.; Hirthammer, M.; Mestdagh, H.; Spyroudis, S.; Vollhardt, K. P. C. AG 1987, 99, 1276.
13. U. S. Patent 3 737 452 (CA 1973, 79, 125 889j).
14. FF 1969, 2, 181.
15. Saucy, G.; Marbet, R. HCA 1967, 50, 1158.
16. Chabardes, P. TL 1988, 29, 6253.
17. Safronov, V. M.; Fasman, A. B.; Vorob'eva, V. I. IZV 1982, 6, 37.
18. Rüttimann, A. C 1986, 40, 290.
19. Clinet, J. C.; Julia, S. JCR(S) 1978, 125.
20. Burrell, G.; Cassidy, F., Evans, J. M.; Lightowler, D.; Stemp, G. JMC 1990, 33, 3023.

John Gordon

Lonza, Visp, Switzerland

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