[6089-04-9]  · C8H12O2  · 3-Tetrahydropyranyloxy-1-propyne  · (MW 140.20)

(lithium derivative useful as a synthon for preparation of substituted propargylic alcohols;1 preparation of a-allenic alcohols;2 synthesis of trans-allylic alcohols3)

Alternate Name: tetrahydro-2-(2-propynyloxy)-2H-pyran.

Physical Data: bp 63-65 °C/9 mmHg, 47-50 °C/3.5-5 mmHg; d 0.997 g cm-3.

Solubility: insol H2O; sol benzene, chloroform, 1,2-dichloroethane, ethanol, ether, acetone, dioxane, THF.

Form Supplied in: colorless liquid; commercially available.

Purification: dried over sodium carbonate and distilled under reduced pressure.

Handling, Storage, and Precautions: combustible liquid; harmful if inhaled, or absorbed through skin; causes severe irritation. The THP ether is stable to base but is hydrolyzed by acids or magnesium sulfate, and should be stored under nitrogen in the refrigerator.

Synthesis of Substituted Propargylic Alcohols.

The 2-tetrahydropyranyl (THP) ether of propargyl alcohol can be metalated to form the lithium or magnesium acetylide, which reacts with various electrophiles (eqs 1-7)1 such as alkyl tosylates,4 alkyl halides,5 oxiranes,6 chloroformates,7 orthoformates,8 aldehydes,9 and ketones.10 The products have been used to synthesize juvenile hormone (JH-I) (eq 1)4 and other natural products (eqs 2 and 3).5,6 Hydroxyalkynoates and protected alkynals are obtained by reactions with chloroformate and orthoformate (eqs 4 and 5).7,8 Reactions of lithiated propargyl THP ether with ketones or aldehydes provide 2-butyne-1,4-diol derivatives,9-13 as exemplified in synthetic routes toward (±)-eupenoxide (eq 6)11 and a benzoquinone (eq 7).12 Coupling reactions with vinyl halides provide precursors of enediynes (eq 8).13

Reduction of the resulting 2-butyne-1,4-diol mono-THP ethers with Lithium Aluminum Hydride gives a-allenic alcohols (eq 9).2,14,15 In contrast, Birch reduction of similar substrates gives trans-2-butene-1,4-diol mono-THP ethers (e.g. eq 10).9 Reaction with cuprates affords a mixture of alkylated allenyl and propargyl alcohols (eq 11).16

Synthesis of trans-Allylic Alcohols via Organotin Reagent.

Radical mediated hydrostannylation of propargyl THP ether gives a vinylstannane which serves as a precursor to the corresponding alkenyllithium reagent (eq 12).3 The corresponding organocopper compound undergoes conjugate addition to cyclopentenones through a mixed cuprate; this sequence has been applied to the synthesis of 11-deoxyprostaglandin E2 (eq 13).3 Cyclic 1,5-dienes are obtained by alkylation of the lithium reagent with a,o-dibromoalkanes followed by deprotection, bromination, and reductive coupling with Tetracarbonylnickel (eq 13).3,17

1. Aldrichim. Acta 1986, 19, 9.
2. Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis; Wiley: New York, 1984; pp 132-135.
3. Corey, E. J.; Wollenberg, R. H. JOC 1975, 40, 2265.
4. Corey, E. J.; Katzenellenbogen, J. A.; Gilman, N. W.; Roman, S. A.; Erickson, B. W. JACS 1968, 90, 5618.
5. (a) Mori, K.; Funaki, Y. T 1985, 41, 2369. (b) Nicolaou, K. C.; Zuccarello, G.; Riemer, C.; Estevez, V. A.; Dai, W.-M. JACS 1992, 114, 7360.
6. Bohlmann, F.; Wegner, P.; Jakupovic, J. T 1984, 40, 2537.
7. Earl, R. A.; Townsend, L. B. OSC 1990, 7, 334.
8. Jones, R. G.; Mann, M. J. JACS 1953, 75, 4048.
9. Wasserman, H. H.; Pearce, B. C. TL 1985, 26, 2237.
10. Shigemasa, Y.; Oikawa, H.; Ohrai, S.; Sashiwa, H.; Saimoto, H. BCJ 1992, 65, 2594.
11. Duke, R. K.; Rickards, R. W. JOC 1984, 49, 1898.
12. (a) Foland, L. D.; Karlsson, J. O.; Perri, S. T.; Schwabe, R.; Xu, S. L.; Patil, S.; Moore, H. W. JACS 1989, 111, 975. (b) Foland, L. D.; Decker, O. H. W.; Moore, H. W. JACS 1989, 111, 989.
13. Magnus, P.; Carter, P.; Elliott, J.; Lewis, R.; Harling, J.; Pitterna, T.; Bauta, W. E.; Fortt, S. JACS 1992, 114, 2544.
14. Théron, F.; Verny, M.; Vessière, R. In The Chemistry of the Carbon-Carbon Triple Bond; Patai, S., Ed; Wiley: New York, 1978; pp 410-417.
15. (a) Cowie, J. S.; Landor, P. D.; Landor, S. R. JCS(P1) 1973, 720. (b) Landor, P. D.; Landor, S. R.; Pepper, E. S. JCS(C) 1967, 185.
16. Claesson, A.; Tämnefors, I.; Olsson, L.-I. TL 1975, 1509.
17. Corey, E. J.; Wat, E. K. W. JACS 1967, 89, 2757.

Tamejiro Hiyama

Tokyo Institute of Technology, Yokohama, Japan

Hiroyuki Saimoto

Tottori University, Japan

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