· (MW 314.44)
(reagent for radical alkynylation of C-H or C-I bonds)
Alternate Name: TIPS-acetylene triflone or TIPS-ethynyl triflone.
Solubility: most aprotic organic solvents.
Form Supplied in: colorless liquid not commercially available.
Analysis of Reagent Purity: reagent must be made fresh.
Handling, Storage, and Precautions: sensitive to free radical sources.
Only two recent papers1,2 have described this reagent, which is used for free radical initiated alkynylation. In the first paper, the direct alkynylation of C-H bonds proceeds as summarized in 1 by the facile C-H bond abstraction by the very electrophilic trifluoromethyl radical 4 generated by cleavage of the CF3SO2 radical (7) and loss of SO2. The alkyl radical 5 so generated reacts with the triflone reagent 2 to form the vinyl radical (6) which in turn eliminates the SO2CF3 radical (7) to propagate the chain and afford the attached alkynyl group in 3.
The TIPS variant in 1 is used not only neat on the cyclic C-H substrates THF, tetrahydrothiophene, and cyclohexane, but also in acetonitrile with adamantane, which substituted exclusively at the tertiary C-H (50% yield). Alkynylation was also successful with distal functionality, i.e. R = (CH2)2OSiR3 and (CH2)3Cl, but the triflone could not be formed with ether functionality closer to the acetylene.
Previously, the alkynylation had been reported3,4 with other attached hydrocarbon groups (R = Ph and n-hexyl in 1). The presence of a second acetylene group in the hydrocarbon group R was successful only with four methylenes, but not less, separating the two acetylenes. However, with enough separation the outer acetylene succeeded with only H-substitution to yield 8 in 2 and the product could be carried through triflation and a second alkynylation to form 9.
The necessary silyl triflone reagents proved difficult or impossible to make with less hindered silanes (TMS or TBDMS) by the reaction of the silyl-acetylene anion (n-BuLi/Et2O/-78 °C) with Tf2O. It was this triflation which failed with the proximal ethers and substituted acetylenes above.
In the second paper,2 the reaction was extended to alkynylate C-I bonds photolytically by the added intermediacy of hexabutyldistannane to generate the radical from the iodide. Bromides were inert in this alkynylation, suggesting that this differential reactivity of the two halogens should prove advantageous in synthetic applications.
The reaction outlined in 3, was conducted photolytically in benzene solution, with the benzene presumably scavenging the trifluoromethyl radical, as it is scavenged in 2. A dozen examples of iodides were successful in yields generally over 60% and with retention of configuration. These room-temperature examples show the reaction to be compatible with such diverse functionality as free hydroxyl, ester, amide, thiazole, and potential b-elimination substrates, and succeeded with primary, secondary, and tertiary iodides.
The special value of the TIPS group lies in its easy removal (TBAF/25 °C/2 h) to make the acetylene available for further substitution. Furthermore, the present availability of the TIPS-protected acetylene triflone should make possible a further exploration of the addition and cycloaddition reactions of the acetylene activated by the strong electron-withdrawing power of the triflone group.
- 1. Xiang, J.; Jiang W.; Fuchs, P. L., Tetrahedron Lett. 1997, 38, 6635.
- 2. Xiang, J.; Fuchs, P. L., Tetrahedron Lett. 1998, 39, 8597.
- 3. Gong, J.; Fuchs, P. L., J. Am. Chem. Soc. 1996, 118, 4486.
- 4. Xiang, J.; Fuchs, P. L., Tetrahedron Lett. 1996, 37, 5269.
James B. Hendrickson
Brandeis University, Waltham, Massachusetts, USA
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