[6089-04-9] · C8H12O2 · 3-Tetrahydropyranyloxy-1-propyne · (MW 140.20)
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.
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
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
Tokyo Institute of Technology, Yokohama, Japan
Tottori University, Japan