Propargyl Alcohol

[107-19-7]  · C3H4O  · Propargyl Alcohol  · (MW 56.07)

(cyclopentenone annulation;1 three-carbon building block for organic synthesis2,3)

Alternate Name: 2-propyn-1-ol.

Physical Data: mp -53 °C; bp 114-115 °C; d 0.963 g cm-3. Monohydrate: fp -20 to -60 °C; d 0.968 g cm-3.

Solubility: insol aliphatic hydrocarbons; sol H2O, benzene, chloroform, 1,2-dichloroethane, ethanol, ether, acetone, dioxane, tetrahydrofuran, pyridine; mod sol carbon tetrachloride.

Form Supplied in: colorless liquid; commercially available.

Purification: commercial material contains a stabilizer. An aq solution of propargyl alcohol can be concentrated by azeotropic distillation with butanol or butyl acetate. Dry over K2CO3 and distil under reduced pressure in the presence of about 1% succinic acid through a column packed with glass helices.

Handling, Storage, and Precautions: this highly toxic reagent causes severe irritation and is readily absorbed through the skin. Flammable liquid. Forms explosive mixtures in air. Use only in a chemical fume hood. Polymerized by heat or base. Distillation just prior to use is recommended.

Preparation of the Dilithium Derivative.

A hexane solution of n-Butyllithium (2 equiv) is added to a THF solution of propargyl alcohol.4 When 1 equiv of n-BuLi is added, the viscosity of the reaction mixture increases. Therefore, more than 3 mL of THF per 1 mmol of propargyl alcohol should be used.

Cyclopentenone Annulation.

The adducts of propargyl alcohol and ketones have been employed as divinyl ketone equivalents for the Nazarov cyclization.1 The particular significance of this reaction is the regio- and stereochemical outcome in cyclopentenone annulation.4 The more substituted a-carbon of 2-methylcyclohexanone is selectively incorporated into a five-membered ring (eq 1). This transformation exhibits stereoselectivity as summarized in eq 2 when applied to alkyl-substituted derivatives of the adduct. These results are explained in terms of the conrotatory ring closure of the thermodynamically most favorable pentadienyl cation intermediates. Analogous reactions have been applied to the total synthesis of (±)-nootkatone (eq 3)5 and (±)-muscopyridine (eq 4).6

Three-Carbon Building Block for Organic Synthesis.

Propargyl alcohol has been widely employed as a C3 building block for homologation (eqs 5-7).7-9 Dihydrofurans are obtained from the adducts of propargyl alcohol and ketones or aldehydes (eq 8).10 Propargyl alcohol has been used for alkylation under acidic conditions (eq 9).11

1. Ramaiah, M. S 1984, 529.
2. Théron, F.; Verny, M.; Vessière, R. In The Chemistry of the Carbon-Carbon Triple Bond; Patai, S., Ed.; Wiley: New York, 1978; pp 381-445.
3. (a) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis; Wiley: New York, 1984; pp 89-178. (b) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes, Allenes and Cumulenes; Elsevier: Amsterdam, 1981. (c) Vartanyan, S. A.; Babanyan, Sh. O. RCR 1967, 36, 670.
4. (a) Hiyama, T; Shinoda, M.; Nozaki, H. JACS 1979, 101, 1599. (b) Hiyama, T.; Shinoda, M.; Saimoto, H.; Nozaki, H. BCJ 1981, 54, 2747.
5. Hiyama, T.; Shinoda, M.; Nozaki, H. TL 1979, 3529.
6. Saimoto, H.; Hiyama, T.; Nozaki, H. TL 1980, 3897.
7. Trost, B. M.; Chan, C.; Ruhter, G. JACS 1987, 109, 3486.
8. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. TL 1975, 4467. (b) Havens, S. J.; Hergenrother, P. M. JOC 1985, 50, 1763.
9. (a) Sato, F.; Kobayashi, Y. OS 1990, 69, 106. (b) Negishi, E.; Zhang, Y.; Cederbaum, F. E.; Webb, M. B. JOC 1986, 51, 4080.
10. (a) Saimoto, H.; Hiyama, T.; Nozaki, H. JACS 1981, 103, 4975. (b) Saimoto, H.; Hiyama, T.; Nozaki, H. BCJ 1983, 56, 3078.
11. Hodes, H. D.; Nicholas, K. M. TL 1978, 4349.

Tamejiro Hiyama

Tokyo Institute of Technology, Yokohama, Japan

Hiroyuki Saimoto

Tottori Univeristy, Japan

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