Science of Synthesis

Hopkinson, M. N.; Gouverneur, V., Science of Synthesis Knowledge Updates, (2011) 2, 122.

The use of (diacetoxyiodo)benzene as an external oxidant enables the oxidative alkynylation of arenes developed by Fuchita and co-workers (see Section ‌3.6.13.1.1.3‌) to be performed under catalytic conditions.[‌77‌] This process allows the direct synthesis of arylacetylenes via both C(sp2)–H and C(sp)–H bond functionalization from substrates not requiring preactivation. As such, it is a powerful alternative to the widely used Sonogashira reaction between alkynes and aryl halides. 1,3,5-Trimethoxybenzene (2 equiv) and methyl propynoate react to afford the corresponding arylacetylene ‌51‌ (R1 = CO2Me) in 72% yield (determined by GC/MS) when treated with chloro(triphenylphosphine)gold(I) (5 mol%) and (diacetoxyiodo)benzene (1.5 equiv) in 1,2-dichloroethane (0.5 M) (‌Scheme 21‌). The addition of 1 equivalent of sodium hydrogen carbonate results in an increase in yield to 85% (determined by GC/MS; 81% isolated yield). Notably, no products resulting from homocoupling of the arene (see Section ‌3.6.13.1.3.2‌)[‌65‌,‌66‌] or hydroarylation of the alkyne[‌78‌] are produced. Alternative oxidants such as tert-butyl hydroperoxide and Selectfluor are not suitable in this process when used in 1,2-dichloroethane. Palladium(II) and copper(I) catalysts lead to recovery of the starting materials. The process can be applied to a variety of electron-rich aromatic and heteroaromatic substrates, including indoles, in generally moderate yields, such as in the preparation of alkynylarenes ‌52‌ (‌Scheme 21‌). Electron-neutral or electron-poor arenes are not suitable substrates for this transformation whereas alkynes not bearing a carbonyl substituent, such as phenylacetylene, result in lower yields.

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References